Sample records for biomaterial mediated neural

  1. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    Directory of Open Access Journals (Sweden)

    Sethuraman Swaminathan


    Full Text Available Abstract Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.

  2. Neural engineering from advanced biomaterials to 3D fabrication techniques

    CERN Document Server

    Kaplan, David


    This book covers the principles of advanced 3D fabrication techniques, stem cells and biomaterials for neural engineering. Renowned contributors cover topics such as neural tissue regeneration, peripheral and central nervous system repair, brain-machine interfaces and in vitro nervous system modeling. Within these areas, focus remains on exciting and emerging technologies such as highly developed neuroprostheses and the communication channels between the brain and prostheses, enabling technologies that are beneficial for development of therapeutic interventions, advanced fabrication techniques such as 3D bioprinting, photolithography, microfluidics, and subtractive fabrication, and the engineering of implantable neural grafts. There is a strong focus on stem cells and 3D bioprinting technologies throughout the book, including working with embryonic, fetal, neonatal, and adult stem cells and a variety of sophisticated 3D bioprinting methods for neural engineering applications. There is also a strong focus on b...

  3. Biomaterials

    NARCIS (Netherlands)

    Van Mourik, P.; Van Dam, J.; Picken, S.J.; Ursem, B.


    The metabolic pathways of living organisms produce biomaterials. Hence, in principle biomaterials are fully sustainable. This does not mean that their processing and application have no impact on the environment, e.g. the recycling of natural rubber remains a problem. Biomaterials are applied in a w

  4. Biomaterials

    CERN Document Server

    Migonney , Véronique


    Discovered in the 20th century, biomaterials have contributed to many of the incredible scientific and technological advancements made in recent decades. This book introduces and details the tenets of biomaterials, their relevance in a various fields, practical applications of their products, and potential advancements of the years to come. A comprehensive resource, the text covers the reasons that certain properties of biomaterials contribute to specific applications, and students and researchers will appreciate this exhaustive textbook.

  5. Biomaterials coated by dental pulp cells as substrate for neural stem cell differentiation. (United States)

    Soria, Jose Miguel; Sancho-Tello, María; Esparza, M Angeles Garcia; Mirabet, Vicente; Bagan, Jose Vicente; Monleón, Manuel; Carda, Carmen


    This study is focused on the development of an in vitro hybrid system, consisting in a polymeric biomaterial covered by a dental pulp cellular stroma that acts as a scaffold offering a neurotrophic support for the subsequent survival and differentiation of neural stem cells. In the first place, the behavior of dental pulp stroma on the polymeric biomaterial based on ethyl acrylate and hydroxy ethyl acrylate copolymer was studied. For this purpose, cells from normal human third molars were grown onto 0.5-mm-diameter biomaterial discs. After cell culture, quantification of neurotrophic factors generated by the stromal cells was performed by means of an ELISA assay. In the second place, survival and differentiation of adult murine neural stem cells on the polymeric biomaterials covered by dental pulp stromal cells was studied. The results show the capacity of dental pulp cells to uniformly coat the majority of the material's surface and to secrete neurotrophic factors that become crucial for a subsequent differentiation of neural stem cells. The use of stromal cells cultured on scaffolding biomaterials provides neurotrophic pumps that may suggest new criteria for the design of cell therapy experiments in animal models to assist the repair of lesions in Central Nervous System.

  6. Multi-compartmental biomaterial scaffolds for patterning neural tissue organoids in models of neurodevelopment and tissue regeneration. (United States)

    McMurtrey, Richard J


    Biomaterials are becoming an essential tool in the study and application of stem cell research. Various types of biomaterials enable three-dimensional culture of stem cells, and, more recently, also enable high-resolution patterning and organization of multicellular architectures. Biomaterials also hold potential to provide many additional advantages over cell transplants alone in regenerative medicine. This article describes novel designs for functionalized biomaterial constructs that guide tissue development to targeted regional identities and structures. Such designs comprise compartmentalized regions in the biomaterial structure that are functionalized with molecular factors that form concentration gradients through the construct and guide stem cell development, axis patterning, and tissue architecture, including rostral/caudal, ventral/dorsal, or medial/lateral identities of the central nervous system. The ability to recapitulate innate developmental processes in a three-dimensional environment and under specific controlled conditions has vital application to advanced models of neurodevelopment and for repair of specific sites of damaged or diseased neural tissue.

  7. Biomaterial nanotopography-mediated cell responses: experiment and modeling

    Directory of Open Access Journals (Sweden)

    Lei Yang


    Full Text Available The rapid development of fabrication and processing technologies in the past two decades has enabled researchers to introduce nanoscale features into materials which, interestingly, have been shown to greatly regulate the behavior and fate of biological cells. In particular, important cell responses (such as adhesion, proliferation, differentiation, migration, and filopodial growth have all been correlated with material nanotopography. Given its great potential, intensive efforts have been made, both experimentally and theoretically, to understand why and how cells respond to nanoscale surface features, and this article reviews recent progress in this field. Specifically, a brief overview on the fabrication and modification techniques to create nanotopography on different materials is given first. After that, a summary of important experimental findings on the mediation of nanoscale surface topography on the behavior of various cells, as well as the underlying mechanism, is provided. Finally, both classical and recently developed approaches for modeling nanotopography-mediated cell adhesion and filopodial growth are reviewed.

  8. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface (United States)

    Ereifej, Evon S.

    Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes

  9. Exploiting bacterial peptide display technology to engineer biomaterials for neural stem cell culture. (United States)

    Little, Lauren E; Dane, Karen Y; Daugherty, Patrick S; Healy, Kevin E; Schaffer, David V


    Stem cells are often cultured on substrates that present extracellular matrix (ECM) proteins; however, the heterogeneous and poorly defined nature of ECM proteins presents challenges both for basic biological investigation of cell-matrix investigations and translational applications of stem cells. Therefore, fully synthetic, defined materials conjugated with bioactive ligands, such as adhesive peptides, are preferable for stem cell biology and engineering. However, identifying novel ligands that engage cellular receptors can be challenging, and we have thus developed a high throughput approach to identify new adhesive ligands. We selected an unbiased bacterial peptide display library for the ability to bind adult neural stem cells (NSCs), and 44 bacterial clones expressing peptides were identified and found to bind to NSCs with high avidity. Of these clones, four contained RGD motifs commonly found in integrin binding domains, and three exhibited homology to ECM proteins. Three peptide clones were chosen for further analysis, and their synthetic analogs were adsorbed on tissue culture polystyrene (TCPS) or grafted onto an interpenetrating polymer network (IPN) for cell culture. These three peptides were found to support neural stem cell self-renewal in defined medium as well as multi-lineage differentiation. Therefore, bacterial peptide display offers unique advantages to isolate bioactive peptides from large, unbiased libraries for applications in biomaterials engineering.

  10. Multi-compartmental biomaterial scaffolds for patterning neural tissue organoids in models of neurodevelopment and tissue regeneration (United States)

    McMurtrey, Richard J


    Biomaterials are becoming an essential tool in the study and application of stem cell research. Various types of biomaterials enable three-dimensional culture of stem cells, and, more recently, also enable high-resolution patterning and organization of multicellular architectures. Biomaterials also hold potential to provide many additional advantages over cell transplants alone in regenerative medicine. This article describes novel designs for functionalized biomaterial constructs that guide tissue development to targeted regional identities and structures. Such designs comprise compartmentalized regions in the biomaterial structure that are functionalized with molecular factors that form concentration gradients through the construct and guide stem cell development, axis patterning, and tissue architecture, including rostral/caudal, ventral/dorsal, or medial/lateral identities of the central nervous system. The ability to recapitulate innate developmental processes in a three-dimensional environment and under specific controlled conditions has vital application to advanced models of neurodevelopment and for repair of specific sites of damaged or diseased neural tissue. PMID:27766141

  11. Multi-compartmental biomaterial scaffolds for patterning neural tissue organoids in models of neurodevelopment and tissue regeneration

    Directory of Open Access Journals (Sweden)

    Richard J McMurtrey


    Full Text Available Biomaterials are becoming an essential tool in the study and application of stem cell research. Various types of biomaterials enable three-dimensional culture of stem cells, and, more recently, also enable high-resolution patterning and organization of multicellular architectures. Biomaterials also hold potential to provide many additional advantages over cell transplants alone in regenerative medicine. This article describes novel designs for functionalized biomaterial constructs that guide tissue development to targeted regional identities and structures. Such designs comprise compartmentalized regions in the biomaterial structure that are functionalized with molecular factors that form concentration gradients through the construct and guide stem cell development, axis patterning, and tissue architecture, including rostral/caudal, ventral/dorsal, or medial/lateral identities of the central nervous system. The ability to recapitulate innate developmental processes in a three-dimensional environment and under specific controlled conditions has vital application to advanced models of neurodevelopment and for repair of specific sites of damaged or diseased neural tissue.

  12. The pivotal role of fibrocytes and mast cells in mediating fibrotic reactions to biomaterials. (United States)

    Thevenot, Paul T; Baker, David W; Weng, Hong; Sun, Man-Wu; Tang, Liping


    Almost all biomaterial implants are surrounded by a fibrotic capsule, although the mechanism of biomaterial-mediated fibrotic reactions is mostly unclear. To search for the types of cells responsible for triggering the tissue responses, we used poly-L glycolic acid polymers capable of releasing various reagents. We first identified that CD45(+)/Collagen 1(+) fibrocytes are recruited and resided within the fibrotic capsule at the implant interface. Interestingly, we found that the recruitment of fibrocytes and the extent of fibrotic tissue formation (collagen type I production) were substantially enhanced and reduced by the localized release of compound 48/80 and cromolyn, respectively. Since it is well established that compound 48/80 and cromolyn alter mast cell reactions, we hypothesized that mast cells are responsible for triggering fibrocyte recruitment and subsequent fibrotic capsule formation surrounding biomaterial implants. To directly test this hypothesis, similar studies were carried out using mast cell deficient mice, WBB6F1/J-Kit(W)/Kit(W-v)/, and their congenic controls. Indeed, mast cell deficient mice prompted substantially less fibrocyte and myofibroblast responses in comparison to C57 wild type mice controls. Most interestingly, subcutaneous mast cell reconstitution of WBB6F1/J-Kit(W)/Kit(W-v)/J mice almost completely restored the fibrocyte response in comparison to the C57 wild type response. These results indicate that the initial biomaterial interaction resulting in the stimulation of mast cells and degranulation byproducts not only stimulates the inflammatory cascade but significantly alters the downstream fibrocyte response and degree of fibrosis.

  13. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid (United States)

    Singh, Anirudha; Corvelli, Michael; Unterman, Shimon A.; Wepasnick, Kevin A.; McDonnell, Peter; Elisseeff, Jennifer H.


    Lubrication is key for the efficient function of devices and tissues with moving surfaces, such as articulating joints, ocular surfaces and the lungs. Indeed, lubrication dysfunction leads to increased friction and degeneration of these systems. Here, we present a polymer-peptide surface coating platform to non-covalently bind hyaluronic acid (HA), a natural lubricant in the body. Tissue surfaces treated with the HA-binding system exhibited higher lubricity values, and in vivo were able to retain HA in the articular joint and to bind ocular tissue surfaces. Biomaterials-mediated strategies that locally bind and concentrate HA could provide physical and biological benefits when used to treat tissue-lubricating dysfunction and to coat medical devices.

  14. Enhanced lubrication on tissue and biomaterial surfaces through peptide-mediated binding of hyaluronic acid. (United States)

    Singh, Anirudha; Corvelli, Michael; Unterman, Shimon A; Wepasnick, Kevin A; McDonnell, Peter; Elisseeff, Jennifer H


    Lubrication is key for the efficient function of devices and tissues with moving surfaces, such as articulating joints, ocular surfaces and the lungs. Indeed, lubrication dysfunction leads to increased friction and degeneration of these systems. Here, we present a polymer-peptide surface coating platform to non-covalently bind hyaluronic acid (HA), a natural lubricant in the body. Tissue surfaces treated with the HA-binding system exhibited higher lubricity values, and in vivo were able to retain HA in the articular joint and to bind ocular tissue surfaces. Biomaterials-mediated strategies that locally bind and concentrate HA could provide physical and biological benefits when used to treat tissue-lubricating dysfunction and to coat medical devices.

  15. Kinetic measurement of esterase-mediated hydrolysis for methacrylate monomers used in dental composite biomaterials (United States)

    Russo, Karen Ann

    Methacrylate-based monomers are routinely used in medical biomaterials. Monomers undergo polymerization reactions to form the solid resin. These polymerization reactions can be incomplete thus making unpolymerized monomer available for possible biodistribution. Understanding the fate of these monomers is essential not only for their toxicological profile but also for development of future biomaterials. Aromatic methacrylate-based monomers included in this study were bisphenol A dimethacrylate and bisphenol A diglycidyl dimethathacrylate; aliphatic methacrylate monomers were 2-hydroxyethyl methacrylate and triethyleneglycol dimethacrylate. These compounds contain ester moieties thought to be susceptible to esterase-mediated hydrolysis. The hypothesis was that the ester bond of the methacrylate monomers can be hydrolyzed by esterases and these reactions would occur in a measurable, time-dependent manner confirmed by specific Michaelis-Menten kinetic relationships. Including aliphatic and aromatic methacrylate monomers in this work allowed for structure-based comparisons. In vitro enzymolysis of the test compounds by acetylcholinesterase and cholesterol esterase was performed in buffered solutions. The hydrolysis reactions were monitored by high performance liquid chromatography with ultraviolet detection. The disappearance of parent compound and appearance of hydrolysis products were quantitated. The aromatic methacrylate monomers, bisphenol A dimethacrylate and bisphenol A diglycidyl dimethacrylate, were resistant to acetylcholine esterase hydrolysis but were converted by cholesterol esterase. The putative xenoestrogen, bisphenol A, was identified as a hydrolysis product from bisphenol A dimethacrylate conversion. Cholesterol esterase induced hydrolysis of bisphenol A diglycidyl dimethacrylate yielded a Km value of 1584 muM and Vmax of 14 muM min-1. Triethyleneglycol was converted by both esterases with calculated Km values of 394 and 1311 muM for acetylcholine

  16. Multi-compartmental biomaterial scaffolds for patterning neural tissue organoids in models of neurodevelopment and tissue regeneration


    McMurtrey, Richard J


    Biomaterials are becoming an essential tool in the study and application of stem cell research. Various types of biomaterials enable three-dimensional culture of stem cells, and, more recently, also enable high-resolution patterning and organization of multicellular architectures. Biomaterials also hold potential to provide many additional advantages over cell transplants alone in regenerative medicine. This article describes novel designs for functionalized biomaterial constructs that guide ...

  17. Neural mediator of the schizotypy-antisocial behavior relationship. (United States)

    Lam, B Y H; Yang, Y; Raine, A; Lee, T M C


    Prior studies have established that schizotypal personality traits (schizotypy) were associated with antisocial behavior (crime), but it is unclear what neural factors mediate this relationship. This study assessed the mediating effect that sub-regional prefrontal gray, specifically the orbitofrontal gray matter volume, has on the schizotypy-antisocial behavior relationship. Five prefrontal sub-regional (superior, middle, inferior, orbitofrontal and rectal gyral) gray matter volumes were assessed using structural magnetic resonance imaging in 90 adults from the community, together with schizotypy and antisocial behavior. Among all five prefrontal sub-regions, the orbitofrontal cortex (OFC) was the major region-of-interest in the present study. Mediation analyses showed that orbitofrontal gray fully mediated the association between schizotypy and antisocial behavior. After having controlled the sex, age, socio-economic statuses, whole brain volumes and substance abuse/dependence of test subjects, the orbitofrontal gray still significantly mediated the effect of schizotypy on antisocial behavior by 53.5%. These findings are the first that document a neural mediator of the schizotypy-antisocial behavior relationship. Findings also suggest that functions subserved by the OFC, including impulse control and inhibition, emotion processing and decision-making, may contribute to the above comorbidity.

  18. Neural mediators of the intergenerational transmission of family aggression


    Saxbe, Darby; Del Piero, Larissa Borofsky; Immordino-Yang, Mary Helen; Kaplan, Jonas Todd; Margolin, Gayla


    Youth exposed to family aggression may become more aggressive themselves, but the mechanisms of intergenerational transmission are understudied. In a longitudinal study, we found that adolescents’ reduced neural activation when rating their parents’ emotions, assessed via magnetic resonance imaging, mediated the association between parents’ past aggression and adolescents’ subsequent aggressive behavior toward parents. A subsample of 21 youth, drawn from the larger study, underwent magnetic r...

  19. LRP2 mediates folate uptake in the developing neural tube. (United States)

    Kur, Esther; Mecklenburg, Nora; Cabrera, Robert M; Willnow, Thomas E; Hammes, Annette


    The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2) is a multifunctional cell-surface receptor expressed in the embryonic neuroepithelium. Loss of LRP2 in the developing murine central nervous system (CNS) causes impaired closure of the rostral neural tube at embryonic stage (E) 9.0. Similar neural tube defects (NTDs) have previously been attributed to impaired folate metabolism in mice. We therefore asked whether LRP2 might be required for the delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole-embryo cultures showed that LRP2-deficient neuroepithelial cells are unable to mediate the uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared with control littermates. Moreover, the folic-acid-dependent gene Alx3 is significantly downregulated in Lrp2 mutants. In conclusion, we show that LRP2 is essential for cellular folate uptake in the developing neural tube, a crucial step for proper neural tube closure.

  20. [Cardiovascular biomaterials]. (United States)

    Loisance, D


    Hemocompatible biomaterials, i.e. materials to be used in a biological environment, are of various origins (biological, synthetic). The great variety of physical and chemical characteristics has allowed design of various prosthesis and artificial organs. Use of biomaterials and artificial organs has made possible the development of substitutive therapies, a growing component of medical care. None of the biomaterials presently used is ideal. Everyone of them is responsible for a local and general reaction: foreign body reaction, coagulation, whole body inflammatory response. For years, these reactions have been poorly understood and development was of a very empirical nature. Progress in cellular and molecular biology permits today a better understanding of the mechanisms involved in these reactions. Use of biomaterials is facing to day a difficult problem; liability concerns threaten further developments and leads to market withdrawal of major basic materials.

  1. Neural stem cell-derived exosomes mediate viral entry

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    Sims B


    Full Text Available Brian Sims,1,2,* Linlin Gu,3,* Alexandre Krendelchtchikov,3 Qiana L Matthews3,4 1Division of Neonatology, Department of Pediatrics, 2Department of Cell, Developmental, and Integrative Biology, 3Division of Infectious Diseases, Department of Medicine, 4Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, USA *These authors contributed equally to this work Background: Viruses enter host cells through interactions of viral ligands with cellular receptors. Viruses can also enter cells in a receptor-independent fashion. Mechanisms regarding the receptor-independent viral entry into cells have not been fully elucidated. Exosomal trafficking between cells may offer a mechanism by which viruses can enter cells.Methods: To investigate the role of exosomes on cellular viral entry, we employed neural stem cell-derived exosomes and adenovirus type 5 (Ad5 for the proof-of-principle study. Results: Exosomes significantly enhanced Ad5 entry in Coxsackie virus and adenovirus receptor (CAR-deficient cells, in which Ad5 only had very limited entry. The exosomes were shown to contain T-cell immunoglobulin mucin protein 4 (TIM-4, which binds phosphatidylserine. Treatment with anti-TIM-4 antibody significantly blocked the exosome-mediated Ad5 entry.Conclusion: Neural stem cell-derived exosomes mediated significant cellular entry of Ad5 in a receptor-independent fashion. This mediation may be hampered by an antibody specifically targeting TIM-4 on exosomes. This set of results will benefit further elucidation of virus/exosome pathways, which would contribute to reducing natural viral infection by developing therapeutic agents or vaccines. Keywords: neural stem cell-derived exosomes, adenovirus type 5, TIM-4, viral entry, phospholipids

  2. Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair. (United States)

    Tseng, Ting-Chen; Hsieh, Fu-Yu; Dai, Niann-Tzyy; Hsu, Shan-Hui


    Cell- and gene-based therapies have emerged as promising strategies for treating neurological diseases. The sources of neural stem cells are limited while the induced pluripotent stem (iPS) cells have risk of tumor formation. Here, we proposed the generation of self-renewable, multipotent, and neural lineage-related neural crest stem-like cells by chitosan substrate-mediated gene transfer of a single factor forkhead box D3 (FOXD3) for the use in neural repair. A simple, non-toxic, substrate-mediated method was applied to deliver the naked FOXD3 plasmid into human fibroblasts. The transfection of FOXD3 increased cell proliferation and up-regulated the neural crest marker genes (FOXD3, SOX2, and CD271), stemness marker genes (OCT4, NANOG, and SOX2), and neural lineage-related genes (Nestin, β-tubulin and GFAP). The expression levels of stemness marker genes and neural crest maker genes in the FOXD3-transfected fibroblasts were maintained until the fifth passage. The FOXD3 reprogrammed fibroblasts based on the new method significantly rescued the neural function of the impaired zebrafish. The chitosan substrate-mediated delivery of naked plasmid showed feasibility in reprogramming somatic cells. Particularly, the FOXD3 reprogrammed fibroblasts hold promise as an easily accessible cellular source with neural crest stem-like behavior for treating neural diseases in the future.

  3. Coding of level of ambiguity within neural systems mediating choice (United States)

    Lopez-Paniagua, Dan; Seger, Carol A.


    Data from previous neuroimaging studies exploring neural activity associated with uncertainty suggest varying levels of activation associated with changing degrees of uncertainty in neural regions that mediate choice behavior. The present study used a novel task that parametrically controlled the amount of information hidden from the subject; levels of uncertainty ranged from full ambiguity (no information about probability of winning) through multiple levels of partial ambiguity, to a condition of risk only (zero ambiguity with full knowledge of the probability of winning). A parametric analysis compared a linear model in which weighting increased as a function of level of ambiguity, and an inverted-U quadratic models in which partial ambiguity conditions were weighted most heavily. Overall we found that risk and all levels of ambiguity recruited a common “fronto—parietal—striatal” network including regions within the dorsolateral prefrontal cortex, intraparietal sulcus, and dorsal striatum. Activation was greatest across these regions and additional anterior and superior prefrontal regions for the quadratic function which most heavily weighs trials with partial ambiguity. These results suggest that the neural regions involved in decision processes do not merely track the absolute degree ambiguity or type of uncertainty (risk vs. ambiguity). Instead, recruitment of prefrontal regions may result from greater degree of difficulty in conditions of partial ambiguity: when information regarding reward probabilities important for decision making is hidden or not easily obtained the subject must engage in a search for tractable information. Additionally, this study identified regions of activity related to the valuation of potential gains associated with stimuli or options (including the orbitofrontal and medial prefrontal cortices and dorsal striatum) and related to winning (including orbitofrontal cortex and ventral striatum). PMID:24367286

  4. Neurally mediated syncope presenting with paroxysmal positional vertigo and tinnitus. (United States)

    Goto, Fumiyuki; Tsutsumi, Tomoko; Nakamura, Iwao; Ogawa, Kaoru


    A 72-year-old man with positional vertigo and tinnitus was referred to us. He did not want to perform provoking test except once due to his fear. No positional nystagmus was provoked. He found that his attacks usually occurred when he lay on his right ear. From his clinical history, benign paroxysmal positional vertigo was suspected. Conventional pharmacotherapy as well as non-specific physical therapy did not have significant effect. His feeling of positional vertigo with pyrosis was actually presyncope. We suspected cardiovascular disorders, and referred him to a cardiologist. Portable cardiogram monitoring revealed paroxysmal bradycardia. He was diagnosed with neurally mediated syncope, and a pacemaker was implanted. His paroxysmal dizziness soon disappeared. It is important to study the clinical history of the patients in detail, as they are not always able to accurately explain their symptoms. We should carefully rule out cardiovascular disorders, especially when we see the patients with suspected BPPV without the characteristic positional nystagmus.

  5. Neural circuits mediating olfactory-driven behavior in fish

    Directory of Open Access Journals (Sweden)

    Florence eKermen


    Full Text Available The fish olfactory system processes odor signals and mediates behaviors that are crucial for survival such as foraging, courtship and alarm response. Although the upstream olfactory brain areas (olfactory epithelium and olfactory bulb are well studied, less is known about their target brain areas and the role they play in generating odor-driven behaviors. Here we review a broad range of literature on the anatomy, physiology and behavioral output of the olfactory system and its target areas in a wide range of teleost fish. Additionally, we discuss how applying recent technological advancements to the zebrafish (Danio rerio could help in understanding the function of these target areas. We hope to provide a framework for elucidating the neural circuit computations underlying the odor-driven behaviors in this small, transparent and genetically amenable vertebrate.

  6. Biological biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Jorge-Herrero, E. [Servicio de Cirugia Experimental. Clinica Puerta de Hierro, Madrid (Spain)


    There are a number of situations in which substances of biological origin are employed as biomaterials. Most of them are macromolecules derived from isolated connective tissue or the connective tissue itself in membrane form, in both cases, the tissue can be used in its natural form or be chemically treated. In other cases, certain blood vessels can be chemically pretreated and used as vascular prostheses. Proteins such as albumin, collagen and fibrinogen are employed to coat vascular prostheses. Certain polysaccharides have also been tested for use in controlled drug release systems. Likewise, a number of tissues, such as dura mater, bovine pericardium, procine valves and human valves, are used in the preparation of cardiac prostheses. We also use veins from animals or humans in arterial replacement. In none of these cases are the tissues employed dissimilar to the native tissues as they have been chemically modified, becoming a new bio material with different physical and biochemical properties. In short, we find that natural products are being utilized as biomaterials and must be considered as such; thus, it is necessary to study both their chemicobiological and physicomechanical properties. In the present report, we review the current applications, problems and future prospects of some of these biological biomaterials. (Author) 84 refs.

  7. Neural mediators of the intergenerational transmission of family aggression. (United States)

    Saxbe, Darby; Del Piero, Larissa Borofsky; Immordino-Yang, Mary Helen; Kaplan, Jonas Todd; Margolin, Gayla


    Youth exposed to family aggression may become more aggressive themselves, but the mechanisms of intergenerational transmission are understudied. In a longitudinal study, we found that adolescents' reduced neural activation when rating their parents' emotions, assessed via magnetic resonance imaging, mediated the association between parents' past aggression and adolescents' subsequent aggressive behavior toward parents. A subsample of 21 youth, drawn from the larger study, underwent magnetic resonance imaging scanning proximate to the second of two assessments of the family environment. At Time 1 (when youth were on average 15.51 years old) we measured parents' aggressive marital and parent-child conflict behaviors, and at Time 2 (≈2 years later), we measured youth aggression directed toward parents. Youth from more aggressive families showed relatively less activation to parent stimuli in brain areas associated with salience and socioemotional processing, including the insula and limbic structures. Activation patterns in these same areas were also associated with youths' subsequent parent-directed aggression. The association between parents' aggression and youths' subsequent parent-directed aggression was statistically mediated by signal change coefficients in the insula, right amygdala, thalamus, and putamen. These signal change coefficients were also positively associated with scores on a mentalizing measure. Hypoarousal of the emotional brain to family stimuli may support the intergenerational transmission of family aggression.

  8. Study of biomaterial-induced macrophage activation, cell-mediated immune response and molecular oxidative damage in patients with dermal bioimplants. (United States)

    Sánchez, Olga; Rodríguez-Sureda, Víctor; Domínguez, Carmen; Fernández-Figueras, Teresa; Vilches, Angel; Llurba, Elisa; Alijotas-Reig, Jaume


    Several soft-tissue dermal fillers have been reported to provoke immunogenicity and may cause adverse reactions despite claims regarding their safety. This study aimed to assess biomaterial-induced macrophage activation, cell-mediated immune response and oxidative stress in 169 patients with dermal bioimplants. To this end, we analysed plasma concentrations of myeloperoxidase (MPO), the chitinase-like proteins chitotriosidase and YKL-40 and molecular oxidative damage. The present study shows, for the first time, that the components of innate immunity: chitotriosidase and YKL-40, are significantly higher in patients with certain bioimplants and these markers of monocyte/macrophage activation rose progressively as adverse reactions (AR) evolved. Plasma MPO levels increased 4-fold in filler users with AR and 3-fold in those without. Analysis by filler type showed subjects injected with calcium hydroxylapatite, methacrylate, acrylamides and silicone to have values significantly above those of non-filler subjects for at least two plasma biomarkers, probably because the afore-mentioned biomaterials are permanent and prone to trigger AR in the long term. By contrast, hyaluronic acid alone elicited little immune response. Plasma concentrations of markers of oxidative damage to lipids and proteins were found to be significantly higher in users of four of the nine dermal fillers studied. These diffusible products of molecular peroxidation would stem from the reaction catalysed by MPO that generates potent oxidants, leading to cell oxidative damage which, in turn, may exert deleterious effects on the organism. Overall, the results of this study on the effects of a range of dermal fillers point to chronic activation of the immune response mediated by macrophages and PMNs. The increases in plasma of MPO, chitotriosidase and YKL-40 proteins and products of macromolecular peroxidation suggests that these molecules could serve as blood-based biochemical markers and alert to the

  9. Prefrontally driven downregulation of neural synchrony mediates goal-directed forgetting. (United States)

    Hanslmayr, Simon; Volberg, Gregor; Wimber, Maria; Oehler, Nora; Staudigl, Tobias; Hartmann, Thomas; Raabe, Markus; Greenlee, Mark W; Bäuml, Karl-Heinz T


    Neural synchronization between distant cell assemblies is crucial for the formation of new memories. To date, however, it remains unclear whether higher-order brain regions can adaptively regulate neural synchrony to control memory processing in humans. We explored this question in two experiments using a voluntary forgetting task. In the first experiment, we simultaneously recorded electroencephalography along with fMRI. The results show that a reduction in neural synchrony goes hand-in-hand with a BOLD signal increase in the left dorsolateral prefrontal cortex (dlPFC) when participants are cued to forget previously studied information. In the second experiment, we directly stimulated the left dlPFC with repetitive transcranial magnetic stimulation during the same task, and show that such stimulation specifically boosts the behavioral forgetting effect and induces a reduction in neural synchrony. These results suggest that prefrontally driven downregulation of long-range neural synchronization mediates goal-directed forgetting of long-term memories.

  10. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications. (United States)

    Grzesiak, Jakub; Marycz, Krzysztof; Szarek, Dariusz; Bednarz, Paulina; Laska, Jadwiga


    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane-polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane-polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells.

  11. Numerical discrimination is mediated by neural coding variation. (United States)

    Prather, Richard W


    One foundation of numerical cognition is that discrimination accuracy depends on the proportional difference between compared values, closely following the Weber-Fechner discrimination law. Performance in non-symbolic numerical discrimination is used to calculate individual Weber fraction, a measure of relative acuity of the approximate number system (ANS). Individual Weber fraction is linked to symbolic arithmetic skills and long-term educational and economic outcomes. The present findings suggest that numerical discrimination performance depends on both the proportional difference and absolute value, deviating from the Weber-Fechner law. The effect of absolute value is predicted via computational model based on the neural correlates of numerical perception. Specifically, that the neural coding "noise" varies across corresponding numerosities. A computational model using firing rate variation based on neural data demonstrates a significant interaction between ratio difference and absolute value in predicting numerical discriminability. We find that both behavioral and computational data show an interaction between ratio difference and absolute value on numerical discrimination accuracy. These results further suggest a reexamination of the mechanisms involved in non-symbolic numerical discrimination, how researchers may measure individual performance, and what outcomes performance may predict.

  12. N-cadherin-mediated cell adhesion restricts cell proliferation in the dorsal neural tube. (United States)

    Chalasani, Kavita; Brewster, Rachel M


    Neural progenitors are organized as a pseudostratified epithelium held together by adherens junctions (AJs), multiprotein complexes composed of cadherins and α- and β-catenin. Catenins are known to control neural progenitor division; however, it is not known whether they function in this capacity as cadherin binding partners, as there is little evidence that cadherins themselves regulate neural proliferation. We show here that zebrafish N-cadherin (N-cad) restricts cell proliferation in the dorsal region of the neural tube by regulating cell-cycle length. We further reveal that N-cad couples cell-cycle exit and differentiation, as a fraction of neurons are mitotic in N-cad mutants. Enhanced proliferation in N-cad mutants is mediated by ligand-independent activation of Hedgehog (Hh) signaling, possibly caused by defective ciliogenesis. Furthermore, depletion of Hh signaling results in the loss of junctional markers. We therefore propose that N-cad restricts the response of dorsal neural progenitors to Hh and that Hh signaling limits the range of its own activity by promoting AJ assembly. Taken together, these observations emphasize a key role for N-cad-mediated adhesion in controlling neural progenitor proliferation. In addition, these findings are the first to demonstrate a requirement for cadherins in synchronizing cell-cycle exit and differentiation and a reciprocal interaction between AJs and Hh signaling.

  13. Polyurethane/polylactide-based biomaterials combined with rat olfactory bulb-derived glial cells and adipose-derived mesenchymal stromal cells for neural regenerative medicine applications

    Energy Technology Data Exchange (ETDEWEB)

    Grzesiak, Jakub, E-mail: [Electron Microscopy Laboratory, University of Environmental and Life Sciences, Kozuchowska 5b, 51-631 Wroclaw (Poland); Marycz, Krzysztof [Electron Microscopy Laboratory, University of Environmental and Life Sciences, Kozuchowska 5b, 51-631 Wroclaw (Poland); Szarek, Dariusz [Department of Neurosurgery, Lower Silesia Specialist Hospital of T. Marciniak, Emergency Medicine Center, Traugutta 116, 50-420 Wroclaw (Poland); Bednarz, Paulina [State Higher Vocational School in Tarnów, Mickiewicza 8, 33-100 Tarnów (Poland); Laska, Jadwiga [AGH University of Science and Technology, Faculty of Materials Science and Ceramics, Mickiewicza 30, 30-059 Kraków (Poland)


    Research concerning the elaboration and application of biomaterial which may support the nerve tissue regeneration is currently one of the most promising directions. Biocompatible polymer devices are noteworthy group among the numerous types of potentially attractive biomaterials for regenerative medicine application. Polylactides and polyurethanes may be utilized for developing devices for supporting the nerve regeneration, like nerve guide conduits or bridges connecting the endings of broken nerve tracts. Moreover, the combination of these biomaterial devices with regenerative cell populations, like stem or precursor cells should significantly improve the final therapeutic effect. Therefore, the composition and structure of final device should support the proper adhesion and growth of cells destined for clinical application. In current research, the three polymer mats elaborated for connecting the broken nerve tracts, made from polylactide, polyurethane and their blend were evaluated both for physical properties and in vitro, using the olfactory-bulb glial cells and mesenchymal stem cells. The evaluation of Young's modulus, wettability and roughness of obtained materials showed the differences between analyzed samples. The analysis of cell adhesion, proliferation and morphology showed that the polyurethane–polylactide blend was the most neutral for cells in culture, while in the pure polymer samples there were significant alterations observed. Our results indicated that polyurethane–polylactide blend is an optimal composition for culturing and delivery of glial and mesenchymal stem cells. - Highlights: • Polyurethane–polylactide blends exhibit different characteristics from pure polymers. • Pure PU and PLA negatively influence on morphology of glial and mesenchymal cells. • PU/PLA blend was neutral for glial and mesenchymal cell proliferation and morphology.

  14. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc


    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  15. Voltammetry of Medical Biomaterials


    Gulaboski, Rubin; Markovski, Velo


    The use of biomaterials in the medicine, dentistry and pharmacy represents probably a major breakthrough in tackling many diseases or disabilities in the last 50 years. We refer to varios techniques that are used for the characterization of the structure and the composition of the biomaterials. Voltammetry is an electrochemical technique that helps mainly in understanding the redox properties of various biomaterials containing some suitable redox centers in their structure. We give in this le...

  16. Voltametry of Biomaterials


    Gulaboski, Rubin; Markovski, Velo


    Any substance that can be used as a replacement for some organ or tissue in the human body is defined as a biomaterial. The use of biomaterials in the medicine, dentistry and pharmacy represents probably a major breakthrough in tackling many diseases or disabilities in the last 50 years. Various techniques are used for the characterization of the structure and the composition of the biomaterials. Of them, the spectroscopic ones are mostly explored. Voltammetry is an electrochemical technique ...

  17. Biodegradation of Silk Biomaterials


    Bochu Wang; Yang Cao


    Silk fibroin from the silkworm, Bombyx mori, has excellent properties such as biocompatibility, biodegradation, non-toxicity, adsorption properties, etc. As a kind of ideal biomaterial, silk fibroin has been widely used since it was first utilized for sutures a long time ago. The degradation behavior of silk biomaterials is obviously important for medical applications. This article will focus on silk-based biomaterials and review the degradation behaviors of silk materials.

  18. Familiarity and priming are mediated by overlapping neural substrates. (United States)

    Thakral, Preston P; Kensinger, Elizabeth A; Slotnick, Scott D


    Explicit memory is widely assumed to reflect the conscious processes of recollection and familiarity. However, familiarity has been hypothesized to be supported by nonconscious processing. In the present functional magnetic resonance imaging (fMRI) experiment, we assessed whether familiarity is mediated by some of the same regions that mediate repetition priming, a form of nonconscious memory. Participants completed an implicit (indirect) memory task and an explicit (direct) memory task during fMRI. During phase I of each task, participants viewed novel abstract shapes with internal colored oriented lines and judged whether each shape was relatively "pleasant" or "unpleasant". During phase II of the indirect memory task, repeated (old) and new shapes were presented and participants made the same judgments. During phase II of the direct memory task, a surprise recognition test was given in which old and new shapes were presented and participants made "remember", "know", or "new" responses. Activity associated with priming was isolated by comparing novel versus repeated shapes during phase II of the indirect memory task. Activity associated with familiarity was isolated by comparing accurate "know" responses versus misses during phase II of the direct memory task. Priming and familiarity were associated with common activity within the superior parietal lobule and motor cortex, which we attribute to shared attentional and motor processing, respectively. The present fMRI results support the hypothesis that familiarity is supported by some of the same processes that support implicit memory.

  19. An introduction to biomaterials

    CERN Document Server

    Hollinger, Jeffrey O


    Consensus Definitions, Fundamental Concepts, and a Standardized Approach to Applied Biomaterials Sciences, J.O. HollingerBiology, Biomechanics, Biomaterial Interactions: Wound Healing BiologyCutaneous Wound Pathobiology: Raison d'etre for Tissue Engineering, L.K. Macri and R.A.F. ClarkOsseous Wound Healing, A. Nawab, M. Wong, D. Kwak, L. Schutte, A. Sharma, and J.O. HollingerBiology, Biomechanics, Biomaterial Interactions: Cellular MechanicsCell and Tissue Mechanobiology, W. Guo, P. Alvarez, and Y. WangBiology, Biomechanics, Biomaterial Interactions: Materials-Host InteractionsCell-Material In

  20. Biomaterials for MEMS

    CERN Document Server

    Chiao, Mu


    This book serves as a guide for practicing engineers, researchers, and students interested in MEMS devices that use biomaterials and biomedical applications. It is also suitable for engineers and researchers interested in MEMS and its applications but who do not have the necessary background in biomaterials.Biomaterials for MEMS highlights important features and issues of biomaterials that have been used in MEMS and biomedical areas. Hence this book is an essential guide for MEMS engineers or researchers who are trained in engineering institutes that do not provide the background or knowledge

  1. Neural stimulation does not mediate attenuated vascular response in ACL-deficient knees: potential role of local inflammatory mediators. (United States)

    Miller, Daniel; Salo, Paul; Hart, David A; Leonard, Catherine; Mammoto, Takeo; Bray, Robert C


    Chronic inflammation associated with osteoarthritis (OA) alters normal responses and modifies the functionality of the articular vasculature. Altered responsiveness of the vasculature may be due to excessive neural activity associated with chronic pain and inflammation, or from the production of inflammatory mediators which induce vasodilation. Using laser speckle perfusion imaging (LSPI), blood flow to the medial collateral ligament (MCL) of adult rabbits was measured in denervated ACL transected knees (n = 6) and compared to unoperated control (n = 6) and 6-week anterial cruciate ligament (ACL)-transected knees (n = 6). Phenylephrine and neuropeptide Y were applied to the MCL vasculature in topical boluses of 100 microL (dose range 10(-14) to 10(-8) mol and 10(-14) to 10(-9) mol, respectively). Denervation diminished vasoconstrictive responsiveness to phenylephrine compared to both control and ACL-transected knees. Denervation minimally enhanced vascular responses to neuropeptide Y (NPY) compared to ACL deficiency alone, which nevertheless remained significantly diminished from control responses. To evaluate the potential role of inflammatory dilators in the diminished contractile responses, phenylephrine was coadministered with histamine, substance P, and prostaglandin E(2). High-dose histamine, and low-dose substance P and PGE(2) were able to inhibit contractile responses in the MCL of control knees. Excessive neural input does not mediate diminished vasoconstrictive responses in the ACL transected knee; inflammatory mediators may play a role in the deficient vascular responsiveness of the ACL transected knee.

  2. Spin-mediated consciousness theory: possible roles of neural membrane nuclear spin ensembles and paramagnetic oxygen. (United States)

    Hu, Huping; Wu, Maoxin


    A novel theory of consciousness is proposed in this paper. We postulate that consciousness is intrinsically connected to quantum spin since the latter is the origin of quantum effects in both Bohm and Hestenes quantum formulism and a fundamental quantum process associated with the structure of space-time. That is, spin is the "mind-pixel". The unity of mind is achieved by entanglement of the mind-pixels. Applying these ideas to the particular structures and dynamics of the brain, we theorize that human brain works as follows: through action potential modulated nuclear spin interactions and paramagnetic O2/NO driven activations, the nuclear spins inside neural membranes and proteins form various entangled quantum states some of which survive decoherence through quantum Zeno effects or in decoherence-free subspaces and then collapse contextually via irreversible and non-computable means producing consciousness and, in turn, the collective spin dynamics associated with said collapses have effects through spin chemistry on classical neural activities thus influencing the neural networks of the brain. Our proposal calls for extension of associative encoding of neural memories to the dynamical structures of neural membranes and proteins. Thus, according our theory, the nuclear spin ensembles are the "mind-screen" with nuclear spins as its pixels, the neural membranes and proteins are the mind-screen and memory matrices, and the biologically available paramagnetic species such as O2 and NO are pixel-activating agents. Together, they form the neural substrates of consciousness. We also present supporting evidence and make important predictions. We stress that our theory is experimentally verifiable with present technologies. Further, experimental realizations of intra-/inter-molecular nuclear spin coherence and entanglement, macroscopic entanglement of spin ensembles and NMR quantum computation, all in room temperatures, strongly suggest the possibility of a spin-mediated

  3. The influence of biomaterials on inflammatory responses to cardiopulmonary bypass. (United States)

    Courtney, J M; Matata, B M; Yin, H Q; Esposito, A; Mahiout, A; Taggart, D P; Lowe, G D


    The nature of cardiopulmonary bypass and the complexity of the inflammatory response make the detection and interpretation of a biomaterial influence difficult. However, if mediation of the inflammatory response is considered to be an appropriate clinical goal, alteration to the biomaterial influence merits further investigation.

  4. GH mediates exercise-dependent activation of SVZ neural precursor cells in aged mice.

    Directory of Open Access Journals (Sweden)

    Daniel G Blackmore

    Full Text Available Here we demonstrate, both in vivo and in vitro, that growth hormone (GH mediates precursor cell activation in the subventricular zone (SVZ of the aged (12-month-old brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation.

  5. Biomaterials in Artificial Organs. (United States)

    Kambic, Helen E.; And Others


    Biomaterials are substances or combinations of substances that can be used in a system that treats, augments, or replaces any tissue, organ, or body function. The nature and role of these substances, particularly in the cadiovascular system, are discussed. (JN)

  6. Biofilm and Dental Biomaterials

    Directory of Open Access Journals (Sweden)

    Marit Øilo


    Full Text Available All treatment involving the use of biomaterials in the body can affect the host in positive or negative ways. The microbiological environment in the oral cavity is affected by the composition and shape of the biomaterials used for oral restorations. This may impair the patients’ oral health and sometimes their general health as well. Many factors determine the composition of the microbiota and the formation of biofilm in relation to biomaterials such as, surface roughness, surface energy and chemical composition, This paper aims to give an overview of the scientific literature regarding the association between the chemical, mechanical and physical properties of dental biomaterials and oral biofilm formation, with emphasis on current research and future perspectives.

  7. Nanostructured Biomaterials for Regeneration**


    Wei, Guobao; Ma, Peter X.


    Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/dysfunctional tissues or organs. Biomaterials (scaffolds) serve as temporary 3D substrates to guide neo tissue formation and organization. It is often beneficial for a scaffolding material to mimic the characteristics of extracellular matrix (ECM) at the nanometer scale and to induce certain natural developmental or/and wound healing processes for tissue regeneration applications. This article...

  8. The experimental study of genetic engineering human neural stem cells mediated by lentivirus to express multigene

    Institute of Scientific and Technical Information of China (English)

    CAI Pei-qiang; TANG Xun; LIN Yue-qiu; Oudega Martin; SUN Guang-yun; XU Lin; YANG Yun-kang; ZHOU Tian-hua


    Objective:To explore the feasibility to construct genetic engineering human neural stem cells (hNSCs)mediated by lentivirus to express multigene in order to provide a graft source for further studies of spinal cord injury (SCI).Methods: Human neural stem cells from the brain cortex of human abortus were isolated and cultured, then gene was modified by lentivirus to express both green fluorescence protein (GFP) and rat neurotrophin-3(NT-3); the transgenic expression was detected by the methods of fluorescence microscope, dorsal root ganglion of fetal rats and slot blot.Results: Genetic engineering hNSCs were successfully constructed. All of the genetic engineering hNSCs which expressed bright green fluorescence were observed under the fluorescence microscope. The conditioned medium of transgenic hNSCs could induce neurite flourishing outgrowth from dorsal root ganglion (DRG). The genetic engineering hNSCs expressed high level NT-3 which could be detected by using slot blot.Conclusions: Genetic engineering hNSCs mediated by lentivirus can be constructed to express multigene successfully.

  9. Advanced biomaterials and biodevices

    CERN Document Server

    Tiwari, Ashutosh


    Biomaterials are the fastest-growing emerging field of  biodevices. Design and development of biomaterials play a significant role in the diagnosis, treatment, and prevention of diseases. Recently, a variety of scaffolds/carriers have been evaluated for tissue regeneration, drug delivery, sensing and imaging.  Liposomes and microspheres have been developed for sustained delivery. Several anti-cancer drugs have been successfully formulated using biomaterial. The targeting of drugs to certain physiological sites has emerged as a promising tool in the treatment with improved drug bioavailability and reduction of dosing frequency. Biodevices-based targeting of drugs may improve the therapeutic success by limiting the adverse drug effects and resulting in more patient compliance and attaining a higher adherence level. Advanced biodevices hold merit as a drug carrier with high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, high stability, as well as the feasibility...

  10. Biomaterials and magnetism

    Indian Academy of Sciences (India)

    D Bahadur; Jyotsnendu Giri


    Magnetism plays an important role in different applications of health care. Magnetite (Fe34) is biocompatible and therefore is one of the most extensively used biomaterials for different applications ranging from cell separation and drug delivery to hyperthermia. Other than this, a large number of magnetic materials in bulk as well as in the form of nano particles have been exploited for a variety of medical applications. In this review, we summarize the salient features of clinical applications, where magnetic biomaterials are used. Magnetic intracellular hyperthermia for cancer therapy is discussed in detail.

  11. Biomaterials and therapeutic applications (United States)

    Ferraro, Angelo


    A number of organic and inorganic, synthetic or natural derived materials have been classified as not harmful for the human body and are appropriate for medical applications. These materials are usually named biomaterials since they are suitable for introduction into living human tissues of prosthesis, as well as for drug delivery, diagnosis, therapies, tissue regeneration and many other clinical applications. Recently, nanomaterials and bioabsorbable polymers have greatly enlarged the fields of application of biomaterials attracting much more the attention of the biomedical community. In this review paper I am going to discuss the most recent advances in the use of magnetic nanoparticles and biodegradable materials as new biomedical tools.

  12. Characterizing biomaterial complexity

    Directory of Open Access Journals (Sweden)

    L.A. Clifton


    Full Text Available Biomaterials research will always require a range of techniques to examine structure and function on a range of length scales and in a range of settings. Neutron scattering provides a unique way of disentangling the molecular and structural complexity of biomaterials through study of the constituent components. We examine how the technique has been used to study surface immobilized proteins and lipid films, floating lipid bilayers as mimics of in vitro planar membranes, and formation of fibres from solution by insects and spiders.

  13. Biomaterial Selection for Tooth Regeneration



    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or s...

  14. Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP (United States)

    Staras, Kevin


    We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture. PMID:27760125

  15. Blockade of microglial KATP -channel abrogates suppression of inflammatory-mediated inhibition of neural precursor cells. (United States)

    Ortega, Francisco J; Vukovic, Jana; Rodríguez, Manuel J; Bartlett, Perry F


    Microglia positively affect neural progenitor cell physiology through the release of inflammatory mediators or trophic factors. We demonstrated previously that reactive microglia foster K(ATP) -channel expression and that blocking this channel using glibenclamide administration enhances striatal neurogenesis after stroke. In this study, we investigated whether the microglial K(ATP) -channel directly influences the activation of neural precursor cells (NPCs) from the subventricular zone using transgenic Csf1r-GFP mice. In vitro exposure of NPCs to lipopolysaccharide and interferon-gamma resulted in a significant decrease in precursor cell number. The complete removal of microglia from the culture or exposure to enriched microglia culture also decreased the precursor cell number. The addition of glibenclamide rescued the negative effects of enriched microglia on neurosphere formation and promoted a ∼20% improvement in precursor cell number. Similar results were found using microglial-conditioned media from isolated microglia. Using primary mixed glial and pure microglial cultures, glibenclamide specifically targeted reactive microglia to restore neurogenesis and increased the microglial production of the chemokine monocyte chemoattractant protein-1 (MCP-1). These findings provide the first direct evidence that the microglial K(ATP) -channel is a regulator of the proliferation of NPCs under inflammatory conditions.

  16. Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP. (United States)

    Shim, Yoonsik; Philippides, Andrew; Staras, Kevin; Husbands, Phil


    We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture.

  17. ACAM, a novel member of the neural IgCAM family, mediates anterior neural tube closure in a primitive chordate. (United States)

    Morales Diaz, Heidi; Mejares, Emil; Newman-Smith, Erin; Smith, William C


    The neural IgCAM family of cell adhesion molecules, which includes NCAM and related molecules, has evolved via gene duplication and alternative splicing to allow for a wide range of isoforms with distinct functions and homophilic binding properties. A search for neural IgCAMs in ascidians (Ciona intestinalis, Ciona savignyi, and Phallusia mammillata) has identified a novel set of truncated family members that, unlike the known members, lack fibronectin III domains and consist of only repeated Ig domains. Within the tunicates this form appears to be unique to the ascidians, and it was designated ACAM, for Ascidian Cell Adhesion Molecule. In C. intestinalis ACAM is expressed in the developing neural plate and neural tube, with strongest expression in the anterior sensory vesicle precursor. Unlike the two other conventional neural IgCAMs in C. intestinalis, which are expressed maternally and throughout the morula and blastula stages, ACAM expression initiates at the gastrula stage. Moreover, C. intestinalis ACAM is a target of the homeodomain transcription factor OTX, which plays an essential role in the development of the anterior central nervous system. Morpholino (MO) knockdown shows that ACAM is required for neural tube closure. In MO-injected embryos neural tube closure was normal caudally, but the anterior neuropore remained open. A similar phenotype was seen with overexpression of a secreted version of ACAM. The presence of ACAM in ascidians highlights the diversity of this gene family in morphogenesis and neurodevelopment.

  18. Identification and dissection of a key enhancer mediating cranial neural crest specific expression of transcription factor, Ets-1. (United States)

    Barembaum, Meyer; Bronner, Marianne E


    Neural crest cells form diverse derivatives that vary according to their level of origin along the body axis, with only cranial neural crest cells contributing to facial skeleton. Interestingly, the transcription factor Ets-1 is uniquely expressed in cranial but not trunk neural crest, where it functions as a direct input into neural crest specifier genes, Sox10 and FoxD3. We have isolated and interrogated a cis-regulatory element, conserved between birds and mammals, that drives reporter expression in a manner that recapitulates that of endogenous Ets-1 expression in the neural crest. Within a minimal Ets-1 enhancer region, mutation of putative binding sites for SoxE, homeobox, Ets, TFAP2 or Fox proteins results in loss or reduction of neural crest enhancer activity. Morpholino-mediated loss-of-function experiments show that Sox9, Pax7, Msx1/2, Ets-1, TFAP2A and FoxD3, all are required for enhancer activity. In contrast, mutation of a putative cMyc/E-box sequence augments reporter expression, consistent with this being a repressor binding site. Taken together, these results uncover new inputs into Ets-1, revealing critical links in the cranial neural crest gene regulatory network.

  19. Graded/Gradient Porous Biomaterials

    Directory of Open Access Journals (Sweden)

    Xigeng Miao


    Full Text Available Biomaterials include bioceramics, biometals, biopolymers and biocomposites and they play important roles in the replacement and regeneration of human tissues. However, dense bioceramics and dense biometals pose the problem of stress shielding due to their high Young’s moduli compared to those of bones. On the other hand, porous biomaterials exhibit the potential of bone ingrowth, which will depend on porous parameters such as pore size, pore interconnectivity, and porosity. Unfortunately, a highly porous biomaterial results in poor mechanical properties. To optimise the mechanical and the biological properties, porous biomaterials with graded/gradient porosity, pores size, and/or composition have been developed. Graded/gradient porous biomaterials have many advantages over graded/gradient dense biomaterials and uniform or homogenous porous biomaterials. The internal pore surfaces of graded/gradient porous biomaterials can be modified with organic, inorganic, or biological coatings and the internal pores themselves can also be filled with biocompatible and biodegradable materials or living cells. However, graded/gradient porous biomaterials are generally more difficult to fabricate than uniform or homogenous porous biomaterials. With the development of cost-effective processing techniques, graded/gradient porous biomaterials can find wide applications in bone defect filling, implant fixation, bone replacement, drug delivery, and tissue engineering.

  20. Permeability transition pore-mediated mitochondrial superoxide flashes regulate cortical neural progenitor differentiation. (United States)

    Hou, Yan; Mattson, Mark P; Cheng, Aiwu


    In the process of neurogenesis, neural progenitor cells (NPCs) cease dividing and differentiate into postmitotic neurons that grow dendrites and an axon, become excitable, and establish synapses with other neurons. Mitochondrial biogenesis and aerobic metabolism provide energy substrates required to support the differentiation, growth and synaptic activity of neurons. Mitochondria may also serve signaling functions and, in this regard, it was recently reported that mitochondria can generate rapid bursts of superoxide (superoxide flashes), the frequency of which changes in response to environmental conditions and signals including oxygen levels and Ca(2+) fluxes. Here we show that the frequency of mitochondrial superoxide flashes increases as embryonic cerebral cortical neurons differentiate from NPCs, and provide evidence that the superoxide flashes serve a signaling function that is critical for the differentiation process. The superoxide flashes are mediated by mitochondrial permeability transition pore (mPTP) opening, and pharmacological inhibition of the mPTP suppresses neuronal differentiation. Moreover, superoxide flashes and neuronal differentiation are inhibited by scavenging of mitochondrial superoxide. Conversely, manipulations that increase superoxide flash frequency accelerate neuronal differentiation. Our findings reveal a regulatory role for mitochondrial superoxide flashes, mediated by mPTP opening, in neuronal differentiation.

  1. Nanomanufacturing of biomaterials

    Directory of Open Access Journals (Sweden)

    Yoni Engel


    Full Text Available In this review, we present a few of the many important objectives in the area of biomedical engineering that could open new pathways for next-generation biomaterials. We also provide examples of how materials for these goals can be created in an economically viable means through recent advances in high throughput production. These strategies highlight the potential for nanomanufacturing in a variety of areas of importance for human health and safety.

  2. Biomaterials surface science

    CERN Document Server

    Taubert, Andreas; Rodriguez-Cabello, José Carlos


    The book provides an overview of the highly interdisciplinary field of surface science in the context of biological and biomedical applications. The covered topics range from micro- and nanostructuring for imparting functionality in a top-down manner to the bottom-up fabrication of gradient surfaces by self-assembly, from interfaces between biomaterials and living matter to smart, stimuli-responsive surfaces, and from cell and surface mechanics to the elucidation of cell-chip interactions in biomedical devices.

  3. NMDA receptors mediate stimulus-timing-dependent plasticity and neural synchrony in the dorsal cochlear nucleus

    Directory of Open Access Journals (Sweden)

    Roxana A Stefanescu


    Full Text Available Auditory information relayed by auditory nerve fibers and somatosensory information relayed by granule cell parallel fibers converge on the fusiform cells (FCs of the dorsal cochlear nucleus, the first brain station of the auditory pathway. In vitro, parallel fiber synapses on FCs exhibit spike-timing-dependent plasticity with Hebbian learning rules, partially mediated by the NMDA receptor (NMDAr. Well-timed bimodal auditory-somatosensory stimulation, in vivo equivalent of spike-timing-dependent plasticity, can induce stimulus-timing-dependent plasticity (StTDP of the FCs spontaneous and tone-evoked firing rates. In healthy guinea pigs, the resulting distribution of StTDP learning rules across a FC neural population is dominated by a Hebbian profile while anti-Hebbian, suppressive and enhancing LRs are less frequent. In this study, we investigate in vivo, the NMDAr contribution to FC baseline activity and long term plasticity. We find that blocking the NMDAr decreases the synchronization of FC- spontaneous activity and mediates differential modulation of FC rate-level functions such that low, and high threshold units are more likely to increase, and decrease, respectively, their maximum amplitudes. Three significant alterations in mean learning-rule profiles were identified: transitions from an initial Hebbian profile towards (1 an anti-Hebbian and (2 a suppressive profile, and (3 transitions from an anti-Hebbian to a Hebbian profile. FC units preserving their learning rules showed instead, NMDAr-dependent plasticity to unimodal acoustic stimulation, with persistent depression of tone-evoked responses changing to persistent enhancement following the NMDAr antagonist. These results reveal a crucial role of the NMDAr in mediating FC baseline activity and long-term plasticity which have important implications for signal processing and auditory pathologies related to maladaptive plasticity of dorsal cochlear nucleus circuitry.

  4. P2X7 receptors mediate innate phagocytosis by human neural precursor cells and neuroblasts. (United States)

    Lovelace, Michael D; Gu, Ben J; Eamegdool, Steven S; Weible, Michael W; Wiley, James S; Allen, David G; Chan-Ling, Tailoi


    During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68(+) microglia and astrocytes mediate phagocytosis during target-dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple-marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live-cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum-free environment, doublecortin(+) (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7(high) DCX(low) hNPCs and P2X7(high) DCX(high) neuroblasts, derived from primary cultures of human fetal telencephalon, phagocytosed targets including latex beads, apoptotic ReNcells, and apoptotic hNPC/neuroblasts. Pretreatment of neuroblasts and hNPCs with 1 mM adenosine triphosphate (ATP), 100 µM OxATP (P2X7 antagonist), or siRNA knockdown of P2X7 inhibited phagocytosis of these targets. Our results show that P2X7 functions as a scavenger receptor under serum-free conditions resembling those in early neurogenesis. This is the first demonstration that hNPCs and neuroblasts may participate in clearance of apoptotic corpses during pre target-dependent neurogenesis and mediate phagocytosis using P2X7 as a scavenger receptor.

  5. Biomaterials by freeze casting. (United States)

    Wegst, Ulrike G K; Schecter, Matthew; Donius, Amalie E; Hunger, Philipp M


    The functional requirements for synthetic tissue substitutes appear deceptively simple: they should provide a porous matrix with interconnecting porosity and surface properties that promote rapid tissue ingrowth; at the same time, they should possess sufficient stiffness, strength and toughness to prevent crushing under physiological loads until full integration and healing are reached. Despite extensive efforts and first encouraging results, current biomaterials for tissue regeneration tend to suffer common limitations: insufficient tissue-material interaction and an inherent lack of strength and toughness associated with porosity. The challenge persists to synthesize materials that mimic both structure and mechanical performance of the natural tissue and permit strong tissue-implant interfaces to be formed. In the case of bone substitute materials, for example, the goal is to engineer high-performance composites with effective properties that, similar to natural mineralized tissue, exceed by orders of magnitude the properties of its constituents. It is still difficult with current technology to emulate in synthetic biomaterials multi-level hierarchical composite structures that are thought to be the origin of the observed mechanical property amplification in biological materials. Freeze casting permits to manufacture such complex, hybrid materials through excellent control of structural and mechanical properties. As a processing technique for the manufacture of biomaterials, freeze casting therefore has great promise.

  6. Biomaterials for craniofacial reconstruction

    Directory of Open Access Journals (Sweden)

    Neumann, Andreas


    Full Text Available Biomaterials for reconstruction of bony defects of the skull comprise of osteosynthetic materials applied after osteotomies or traumatic fractures and materials to fill bony defects which result from malformation, trauma or tumor resections. Other applications concern functional augmentations for dental implants or aesthetic augmentations in the facial region.For ostheosynthesis, mini- and microplates made from titanium alloys provide major advantages concerning biocompatibility, stability and individual fitting to the implant bed. The necessity of removing asymptomatic plates and screws after fracture healing is still a controversial issue. Risks and costs of secondary surgery for removal face a low rate of complications (due to corrosion products when the material remains in situ. Resorbable osteosynthesis systems have similar mechanical stability and are especially useful in the growing skull.The huge variety of biomaterials for the reconstruction of bony defects makes it difficult to decide which material is adequate for which indication and for which site. The optimal biomaterial that meets every requirement (e.g. biocompatibility, stability, intraoperative fitting, product safety, low costs etc. does not exist. The different material types are (autogenic bone and many alloplastics such as metals (mainly titanium, ceramics, plastics and composites. Future developments aim to improve physical and biological properties, especially regarding surface interactions. To date, tissue engineered bone is far from routine clinical application.

  7. Biomaterials in light amplification (United States)

    Mysliwiec, Jaroslaw; Cyprych, Konrad; Sznitko, Lech; Miniewicz, Andrzej


    Biologically produced or inspired materials can serve as optical gain media, i.e. they can exhibit the phenomenon of light amplification. Some of these materials, under suitable dye-doping and optical pumping conditions, show lasing phenomena. The emerging branch of research focused on obtaining lasing action in highly disordered and highly light scattering materials, i.e. research on random lasing, is perfectly suited for biological materials. The use of biomaterials in light amplification has been extensively reported in the literature. In this review we attempt to report on progress in the development of biologically derived systems able to show the phenomena of light amplification and random lasing together with the contribution of our group to this field. The rich world of biopolymers modified with molecular aggregates and nanocrystals, and self-organized at the nanoscale, offers a multitude of possibilities for tailoring luminescent and light scattering properties that are not easily replicated in conventional organic or inorganic materials. Of particular importance and interest are light amplification and lasing, or random lasing studies in biological cells and tissues. In this review we will describe nucleic acids and their complexes employed as gain media due to their favorable optical properties and ease of manipulation. We will report on research conducted on various biomaterials showing structural analogy to nucleic acids such as fluorescent proteins, gelatins in which the first distributed feedback laser was realized, and also amyloids or silks, which, due to their dye-doped fiber-like structure, allow for light amplification. Other materials that were investigated in that respect include polysaccharides, like starch exhibiting favorable photostability in comparison to other biomaterials, and chitosan, which forms photonic crystals or cellulose. Light amplification and random lasing was not only observed in processed biomaterials but also in living

  8. Mechanistic investigation of a hemostatic keratin biomaterial (United States)

    Rahmany, Maria Bahawdory

    Traumatic injury leads to more productive years lost than heart disease, cancer and stroke combined. Trauma is often accompanied and complicated by uncontrolled bleeding. Human hair keratin biomaterials have demonstrated efficacy in controlling hemorrhage in both small and large animal models; however little is known about the mechanism by which these proteins aid in blood clotting. Inspection of the amino acid sequence of known keratins shows the presence of several cellular binding motifs, suggesting a possible mechanism and potentially eliminating the need to functionalize the material's surface for cellular interaction. In addition to small animal studies, the hemostatic activity of keratin hydrogels was explored through porcine hemorrhage models representing both a high flow and low flow bleed. In both studies, keratin hydrogels appeared to lead to a significant reduction in blood loss. The promising results from these in vivo studies provided the motivation for this project. The objective of this dissertation work was to assess the mechanism of action of a hemostatic keratin biomaterial, and more broadly assess the biomaterial-cellular interaction(s). It is our hypothesis that keratin biomaterials have the capacity to specifically interact with cells and lead to propagation of intracellular signaling pathway, specifically contributing to hemostasis. Through application of biochemical and molecular tools, we demonstrate here that keratin biomaterials contribute to hemostasis through two probable mechanisms; integrin mediated platelet adhesion and increased fibrin polymerization. Platelets are the major cell type involved in coagulation both by acting as a catalytic surface for the clotting cascade and adhering to extracellular matrix (ECM) proteins providing a soft platelet plug. Because keratin biomaterials have structural and biochemical characteristics similar to ECM proteins, we utilized several adhesion assays to investigate platelet adhesion to keratin

  9. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa;


    Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  10. Integrated Biomaterials in Tissue Engineering

    CERN Document Server

    Ramalingam, Murugan; Ramakrishna, Seeram; Kobayashi, Hisatoshi; Haikel, Youssef


    "Integrated Biomaterials in Tissue Engineering" features all aspects from fundamental principles to current technological advances in biomaterials at the macro/micro/nano/molecular scales suitable for tissue engineering and regenerative medicine. The book is unique as it provides all important aspects dealing with the basic science involved in structure and properties, techniques and technological innovations in material processing and characterizations, and applications of biomaterials in tissue engineering and regenerative medicine.

  11. Implantable Loop Recorder: Diagnostic Yield And Possible Therapeutic Effect In Patients With Neurally Mediated Reflex Syncope. (United States)

    M, Unterhuber; W, Rauhe; P, Sgobino; F, Pescoller; M, Manfrin; M, Tomaino


    Through a retrospective study concerning the experience of our center in patients affected by Neurally Mediated reflex Syncope (NMS) we wanted to verify not only the diagnostic yield of the Implantable Loop Recorder (ILR) but its possible placebo therapeutic effect. In the context of patients affected by a severe clinical presentation of NMS identified through a careful clinical evaluation, we selected those who followed a diagnostic iter using the ILR. We analysed 84 patients (39 male and 45 female, mean age 71 years), during the period 2009-2013. 34 patients (40.5%) had no recurrences after a mean follow-up (FU) of 35 months, among these 17 concluded a FU of 4 years. 50 patients (59.5%) had recurrences and a specific diagnosis after an average period of 7 months. We found an important number of patients who showed a disappearance of syncope during an observation period of 2-3 and 4 years. At first glance this results could be explained considering the possible placebo therapeutic effect of ILR.

  12. Mediation of autophagic cell death by type 3 ryanodine receptor (RyR3 in adult hippocampal neural stem cells

    Directory of Open Access Journals (Sweden)

    Kyung Min eChung


    Full Text Available Cytoplasmic Ca2+ actively engages in diverse intracellular processes from protein synthesis, folding and trafficking to cell survival and death. Dysregulation of intracellular Ca2+ levels is observed in various neuropathological states including Alzheimer’s and Parkinson’s diseases. Ryanodine receptors (RyRs and IP3 receptors (IP3Rs, the main Ca2+ release channels located in endoplasmic reticulum (ER membranes, are known to direct various cellular events such as autophagy and apoptosis. Here we investigated the intracellular Ca2+-mediated regulation of survival and death of adult hippocampal neural stem (HCN cells utilizing an insulin withdrawal model of autophagic cell death. Despite comparable expression levels of RyR and IP3R transcripts in HCN cells at normal state, the expression levels of RyRs — especially RyR3 — were markedly upregulated upon insulin withdrawal. While treatment with the RyR agonist caffeine significantly promoted the autophagic death of insulin-deficient HCN cells, treatment with its inhibitor dantrolene prevented the induction of autophagy following insulin withdrawal. Furthermore, CRISPR/Cas9-mediated knockout of the RyR3 gene abolished autophagic cell death of HCN cells. This study delineates a distinct, RyR3-mediated ER Ca2+ regulation of autophagy and programmed cell death in neural stem cells. Our findings provide novel insights into the critical, yet understudied mechanisms underlying the regulatory function of ER Ca2+ in neural stem cell biology.

  13. Chapter 6: Degradation of Biomaterials

    NARCIS (Netherlands)

    Davison, N.L.; Barrere-de Groot, F.YF.; Grijpma, D.W.; Blitterswijk, van C.A.; Boer, de J.


    The tissue engineering approach requires suitable biomaterials to serve as three-dimensional scaffolds to support cell growth and differentiation into functional tissues. Depending on the type of tissue in need of repair, a biomaterial must be designed with specific performance criteria in mind. Sev

  14. Self-awareness in neurodegenerative disease relies on neural structures mediating reward-driven attention. (United States)

    Shany-Ur, Tal; Lin, Nancy; Rosen, Howard J; Sollberger, Marc; Miller, Bruce L; Rankin, Katherine P


    versus exaggerating deficits, overestimation and underestimation scores were analysed separately, controlling for age, sex, total intracranial volume and extent of actual functional decline. Atrophy related to overestimating one's functioning included bilateral, right greater than left frontal and subcortical regions, including dorsal superior and middle frontal gyri, lateral and medial orbitofrontal gyri, right anterior insula, putamen, thalamus, and caudate, and midbrain and pons. Thus, our patients' tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge. The anatomic correlates of underestimation (right rostral anterior cingulate cortex, uncorrected significance level) were distinct from overestimation and had a substantially smaller effect size. This suggests that underestimation or 'tarnishing' may be influenced by non-structural neurobiological and sociocultural factors, and should not be considered to be on a continuum with overestimation or 'polishing' of functional capacity, which appears to be more directly mediated by neural circuit dysfunction.

  15. Lymphotropic Virions Affect Chemokine Receptor-Mediated Neural Signaling and Apoptosis: Implications for Human Immunodeficiency Virus Type 1-Associated Dementia (United States)

    Zheng, Jialin; Ghorpade, Anuja; Niemann, Douglas; Cotter, Robin L.; Thylin, Michael R.; Epstein, Leon; Swartz, Jennifer M.; Shepard, Robin B.; Liu, Xiaojuan; Nukuna, Adeline; Gendelman, Howard E.


    Chemokine receptors pivotal for human immunodeficiency virus type 1 (HIV-1) infection in lymphocytes and macrophages (CCR3, CCR5, and CXCR4) are expressed on neural cells (microglia, astrocytes, and/or neurons). It is these cells which are damaged during progressive HIV-1 infection of the central nervous system. We theorize that viral coreceptors could effect neural cell damage during HIV-1-associated dementia (HAD) without simultaneously affecting viral replication. To these ends, we studied the ability of diverse viral strains to affect intracellular signaling and apoptosis of neurons, astrocytes, and monocyte-derived macrophages. Inhibition of cyclic AMP, activation of inositol 1,4,5-trisphosphate, and apoptosis were induced by diverse HIV-1 strains, principally in neurons. Virions from T-cell-tropic (T-tropic) strains (MN, IIIB, and Lai) produced the most significant alterations in signaling of neurons and astrocytes. The HIV-1 envelope glycoprotein, gp120, induced markedly less neural damage than purified virions. Macrophage-tropic (M-tropic) strains (ADA, JR-FL, Bal, MS-CSF, and DJV) produced the least neural damage, while 89.6, a dual-tropic HIV-1 strain, elicited intermediate neural cell damage. All T-tropic strain-mediated neuronal impairments were blocked by the CXCR4 antibody, 12G5. In contrast, the M-tropic strains were only partially blocked by 12G5. CXCR4-mediated neuronal apoptosis was confirmed in pure populations of rat cerebellar granule neurons and was blocked by HA1004, an inhibitor of calcium/calmodulin-dependent protein kinase II, protein kinase A, and protein kinase C. Taken together, these results suggest that progeny HIV-1 virions can influence neuronal signal transduction and apoptosis. This process occurs, in part, through CXCR4 and is independent of CD4 binding. T-tropic viruses that traffic in and out of the brain during progressive HIV-1 disease may play an important role in HAD neuropathogenesis. PMID:10482576

  16. Neural crest-mediated bone resorption is a determinant of species-specific jaw length. (United States)

    Ealba, Erin L; Jheon, Andrew H; Hall, Jane; Curantz, Camille; Butcher, Kristin D; Schneider, Richard A


    Precise control of jaw length during development is crucial for proper form and function. Previously we have shown that in birds, neural crest mesenchyme (NCM) confers species-specific size and shape to the beak by regulating molecular and histological programs for the induction and deposition of cartilage and bone. Here we reveal that a hitherto unrecognized but similarly essential mechanism for establishing jaw length is the ability of NCM to mediate bone resorption. Osteoclasts are considered the predominant cells that resorb bone, although osteocytes have also been shown to participate in this process. In adults, bone resorption is tightly coupled to bone deposition as a means to maintain skeletal homeostasis. Yet, the role and regulation of bone resorption during growth of the embryonic skeleton have remained relatively unexplored. We compare jaw development in short-beaked quail versus long-billed duck and find that quail have substantially higher levels of enzymes expressed by bone-resorbing cells including tartrate-resistant acid phosphatase (TRAP), Matrix metalloproteinase 13 (Mmp13), and Mmp9. Then, we transplant NCM destined to form the jaw skeleton from quail to duck and generate chimeras in which osteocytes arise from quail donor NCM and osteoclasts come exclusively from the duck host. Chimeras develop quail-like jaw skeletons coincident with dramatically elevated expression of TRAP, Mmp13, and Mmp9. To test for a link between bone resorption and jaw length, we block resorption using a bisphosphonate, osteoprotegerin protein, or an MMP13 inhibitor, and this significantly lengthens the jaw. Conversely, activating resorption with RANKL protein shortens the jaw. Finally, we find that higher resorption in quail presages their relatively lower adult jaw bone mineral density (BMD) and that BMD is also NCM-mediated. Thus, our experiments suggest that NCM not only controls bone resorption by its own derivatives but also modulates the activity of mesoderm

  17. The neural mechanisms of affect infusion in social economic decision-making: a mediating role of the anterior insula. (United States)

    Harlé, Katia M; Chang, Luke J; van 't Wout, Mascha; Sanfey, Alan G


    Though emotions have been shown to have sometimes dramatic effects on decision-making, the neural mechanisms mediating these biases are relatively unexplored. Here, we investigated how incidental affect (i.e. emotional states unrelated to the decision at hand) may influence decisions, and how these biases are implemented in the brain. Nineteen adult participants made decisions which involved accepting or rejecting monetary offers from others in an Ultimatum Game while undergoing functional magnetic resonance imaging (fMRI). Prior to each set of decisions, participants watched a short video clip aimed at inducing either a sad or neutral emotional state. Results demonstrated that, as expected, sad participants rejected more unfair offers than those in the neutral condition. Neuroimaging analyses revealed that receiving unfair offers while in a sad mood elicited activity in brain areas related to aversive emotional states and somatosensory integration (anterior insula) and to cognitive conflict (anterior cingulate cortex). Sad participants also showed a diminished sensitivity in neural regions associated with reward processing (ventral striatum). Importantly, insular activation uniquely mediated the relationship between sadness and decision bias. This study is the first to reveal how subtle mood states can be integrated at the neural level to influence decision-making.

  18. Biomaterials. The Behavior of Stainless Steel as a Biomaterial

    Directory of Open Access Journals (Sweden)

    Sanda VISAN


    Full Text Available The biomaterials belong to the broad range of biocompatible chemical substances (sometimes even an element, which can be used for a period of time to treat or replace a tissue, organ or function of the human body. These materials bring many advantages in the diagnosis, prevention and medical therapy, reducing downtime for patients, restoring their biological functions, improving hospital management. The market in Romania sells a wide range of biomaterials for dental, cardiovascular medicine, renal, etc. Scientific research contributes to the discovery of new biomaterials or testing known biomaterials, for finding new applications. The paper exemplifies this contribution by presenting the testing of passive stainless steel behaviour in albumin solution using technique of cyclic voltammetry. It was shown that passivation contribute to increased stability of stainless steel implants to corrosive body fluids.

  19. Zirconia as a Dental Biomaterial

    Directory of Open Access Journals (Sweden)

    Alvaro Della Bona


    Full Text Available Ceramics are very important in the science of dental biomaterials. Among all dental ceramics, zirconia is in evidence as a dental biomaterial and it is the material of choice in contemporary restorative dentistry. Zirconia has been applied as structural material for dental bridges, crowns, inserts, and implants, mostly because of its biocompatibility, high fracture toughness, and radiopacity. However, the clinical success of restorative dentistry has to consider the adhesion to different substrates, which has offered a great challenge to dental zirconia research and development. This study characterizes zirconia as a dental biomaterial, presenting the current consensus and challenges to its dental applications.

  20. Calcium Phosphate Biomaterials: An Update

    Institute of Scientific and Technical Information of China (English)


    Current calcium phosphate (CaP) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricalcium phosphate ( β-TCP ) , biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of composites (CaP/polymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses. This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity, osteoconductivity, osteoinductivity.

  1. Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM and Cell Adhesion Molecules, Extracellular Matrix Proteins, and Viruses

    DEFF Research Database (Denmark)

    Nielsen, Janne; Kulahin, Nikolaj; Walmod, Peter


    Cell adhesion molecules (CAMs) mediate cell-to-cell interactions and interactions between cells and the extracellular matrix (ECM). The neural cell adhesion molecule (NCAM), a prototypic member of the immunoglobulin (Ig) superfamily of CAMs, mediates adhesion through homophilic and heterophilic i...

  2. In vitro evaluation of inorganic and methyl mercury mediated cytotoxic effect on neural cells derived from different animal species. (United States)

    Tong, Jing; Wang, Youwei; Lu, Yuanan


    To extend the current understanding of the mercury-mediated cytotoxic effect, five neural cell lines established from different animal species were comparatively analyzed using three different endpoint bioassays: thiazolyl blue tetrazolium bromide, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT), neutral red uptake assay (NRU), and Coomassie blue assay (CB). Following a 24-hr exposure to selected concentrations of mercury chloride (HgCl2) and methylmercury (II) chloride (MeHgCl), the cytotoxic effect on test cells was characterized by comparing their 50% inhibition concentration (IC50) values. Experimental results indicated that both these forms of mercury were toxic to all the neural cells, but at very different degrees. The IC50 values of MeHgCl among these cell lines ranged from 1.15±0.22 to 10.31±0.70μmol/L while the IC50 values for HgCl2 were much higher, ranging from 6.44±0.36 to 160.97±19.63μmol/L, indicating the more toxic nature of MeHgCl. The IC50 ratio between HgCl2 and MeHgCl ranged from 1.75 to 96.0, which confirms that organic mercury is much more toxic to these neural cells than inorganic mercury. Among these cell lines, HGST-BR and TriG44 derived from marine sea turtles showed a significantly high tolerance to HgCl2 as compared to the three mammalian neural cells. Among these neural cells, SK-N-SH represented the most sensitive cells to both chemical forms of mercury.

  3. Special Issue "Biomaterials and Bioprinting". (United States)

    Chua, Chee Kai; Yeong, Wai Yee; An, Jia


    The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm shift. This Special Issue focuses on biomaterials and bioprinting and contains eight articles covering a number of recent topics in this emerging area.

  4. Zirconia as a Dental Biomaterial


    Alvaro Della Bona; Pecho, Oscar E.; Rodrigo Alessandretti


    Ceramics are very important in the science of dental biomaterials. Among all dental ceramics, zirconia is in evidence as a dental biomaterial and it is the material of choice in contemporary restorative dentistry. Zirconia has been applied as structural material for dental bridges, crowns, inserts, and implants, mostly because of its biocompatibility, high fracture toughness, and radiopacity. However, the clinical success of restorative dentistry has to consider the adhesion to different subs...

  5. Vasoactive intestinal peptide is a local mediator in a gut-brain neural axis activating intestinal gluconeogenesis. (United States)

    De Vadder, F; Plessier, F; Gautier-Stein, A; Mithieux, G


    Intestinal gluconeogenesis (IGN) promotes metabolic benefits through activation of a gut-brain neural axis. However, the local mediator activating gluconeogenic genes in the enterocytes remains unknown. We show that (i) vasoactive intestinal peptide (VIP) signaling through VPAC1 receptor activates the intestinal glucose-6-phosphatase gene in vivo, (ii) the activation of IGN by propionate is counteracted by VPAC1 antagonism, and (iii) VIP-positive intrinsic neurons in the submucosal plexus are increased under the action of propionate. These data support the role of VIP as a local neuromodulator released by intrinsic enteric neurons and responsible for the induction of IGN through a VPAC1 receptor-dependent mechanism in enterocytes.

  6. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain. (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan


    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy.

  7. Ultrasound microbubbles combined with liposome-mediated pNogo-R shRNA delivery into neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Weixia Ye; Xueping Huang; Yangyang Sun; Hao Liu; Jin Jiang; Youde Cao


    In the present study, ultrasound-mediated microbubble destruction (UMMD) alone and combined with liposome technology was used as a novel nonviral technique to transfect a Nogo receptor (Nogo-R) shRNA plasmid (pNogo-R shRNA) into neural stem cells (NSCs). Using green fluorescent protein as a reporter gene, transfection efficiency of NSCs was significantly higher in the group transfected with UMMD combined with liposomes compared with that of the group transfected with UMMD or liposomes alone, and did not affect cell vitality. In addition, Nogo-R mRNA and protein expression was dramatically decreased in the UMMD combined with liposome-mediated group compared with that of other groups after 24 hours of transfection. The UMMD technique combined with liposomes is a noninvasive gene transfer method, which showed minimal effects on cell viability and effectively increased transfer of Nogo-R shRNA into NSCs.

  8. Ultrasound microbubbles combined with liposome-mediated pNogo-R shRNA delivery into neural stem cells. (United States)

    Ye, Weixia; Huang, Xueping; Sun, Yangyang; Liu, Hao; Jiang, Jin; Cao, Youde


    In the present study, ultrasound-mediated microbubble destruction (UMMD) alone and combined with liposome technology was used as a novel nonviral technique to transfect a Nogo receptor (Nogo-R) shRNA plasmid (pNogo-R shRNA) into neural stem cells (NSCs). Using green fluorescent protein as a reporter gene, transfection efficiency of NSCs was significantly higher in the group transfected with UMMD combined with liposomes compared with that of the group transfected with UMMD or liposomes alone, and did not affect cell vitality. In addition, Nogo-R mRNA and protein expression was dramatically decreased in the UMMD combined with liposome-mediated group compared with that of other groups after 24 hours of transfection. The UMMD technique combined with liposomes is a noninvasive gene transfer method, which showed minimal effects on cell viability and effectively increased transfer of Nogo-R shRNA into NSCs.

  9. Rest-mediated regulation of extracellular matrix is crucial for neural development.

    Directory of Open Access Journals (Sweden)

    Yuh-Man Sun

    Full Text Available Neural development from blastocysts is strictly controlled by intricate transcriptional programmes that initiate the down-regulation of pluripotent genes, Oct4, Nanog and Rex1 in blastocysts followed by up-regulation of lineage-specific genes as neural development proceeds. Here, we demonstrate that the expression pattern of the transcription factor Rest mirrors those of pluripotent genes during neural development from embryonic stem (ES cells and an early abrogation of Rest in ES cells using a combination of gene targeting and RNAi approaches causes defects in this process. Specifically, Rest ablation does not alter ES cell pluripotency, but impedes the production of Nestin(+ neural stem cells, neural progenitor cells and neurons, and results in defective adhesion, decrease in cell proliferation, increase in cell death and neuronal phenotypic defects typified by a reduction in migration and neurite elaboration. We also show that these Rest-null phenotypes are due to the dysregulation of its direct or indirect target genes, Lama1, Lamb1, Lamc1 and Lama2 and that these aberrant phenotypes can be rescued by laminins.

  10. Calgary score and modified Calgary score in the differential diagnosis between neurally mediated syncope and epilepsy in children. (United States)

    Zou, Runmei; Wang, Shuo; Zhu, Liping; Wu, Lijia; Lin, Ping; Li, Fang; Xie, Zhenwu; Li, Xiaohong; Wang, Cheng


    To evaluate the value of Calgary score and modified Calgary score in differential diagnosis between neurally mediated syncope and epilepsy in children. 201 children experienced one or more episodes of loss of consciousness and diagnosed as neurally mediated syncope or epilepsy were enrolled. Calgary score, modified Calgary score and receiver-operating characteristic curve were used to explore the predictive value in differential diagnosis. There were significant differences in median Calgary score between syncope [-4.00 (-6, 1)] and epilepsy [2 (-3, 5)] (z = -11.63, P epilepsy were 91.46 and 95.80 %, suggesting a diagnosis of epilepsy. There were significant differences in median modified Calgary score between syncope [-4.00 (-6, 1)] and epilepsy [3 (-3, 6)] (z = -11.71, P epilepsy. The sensitivity and specificity of modified Calgary score and Calgary score did not show significant differences (P > 0.05). Calgary score and modified Calgary score could be used to differential diagnosis between syncope and epilepsy in children.

  11. Host response to biomaterials the impact of host response on biomaterial selection

    CERN Document Server

    Badylak, Stephen F


    Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection explains the various categories of biomaterials and their significance for clinical applications, focusing on the host response to each biomaterial. It is one of the first books to connect immunology and biomaterials with regard to host response. The text also explores the role of the immune system in host response, and covers the regulatory environment for biomaterials, along with the benefits of synthetic versus natural biomaterials, and the transition from simple to complex biomaterial solutions. Fiel

  12. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  13. Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration. (United States)

    Rodrigo Albors, Aida; Tazaki, Akira; Rost, Fabian; Nowoshilow, Sergej; Chara, Osvaldo; Tanaka, Elly M


    Axolotls are uniquely able to mobilize neural stem cells to regenerate all missing regions of the spinal cord. How a neural stem cell under homeostasis converts after injury to a highly regenerative cell remains unknown. Here, we show that during regeneration, axolotl neural stem cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial cells. This dedifferentiation includes the acquisition of rapid cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative stem cell that restores missing tissue.

  14. Neural circuit changes mediating lasting brain and behavioral response to predator stress. (United States)

    Adamec, Robert E; Blundell, Jacqueline; Burton, Paul


    This paper reviews recent work which points to critical neural circuitry involved in lasting changes in anxiety like behavior following unprotected exposure of rats to cats (predator stress). Predator stress may increase anxiety like behavior in a variety of behavioral tests including: elevated plus maze, light dark box, acoustic startle, and social interaction. Studies of neural transmission in two limbic pathways, combined with path and covariance analysis relating physiology to behavior, suggest long term potentiation like changes in one or both of these pathways in the right hemisphere accounts for stress induced changes in all behaviors changed by predator stress except light dark box and social interaction. Findings will be discussed within the context of what is known about neural substrates activated by predator odor.

  15. Biomaterial selection for tooth regeneration. (United States)

    Yuan, Zhenglin; Nie, Hemin; Wang, Shuang; Lee, Chang Hun; Li, Ang; Fu, Susan Y; Zhou, Hong; Chen, Lili; Mao, Jeremy J


    Biomaterials are native or synthetic polymers that act as carriers for drug delivery or scaffolds for tissue regeneration. When implanted in vivo, biomaterials should be nontoxic and exert intended functions. For tooth regeneration, biomaterials have primarily served as a scaffold for (1) transplanted stem cells and/or (2) recruitment of endogenous stem cells. This article critically synthesizes our knowledge of biomaterial use in tooth regeneration, including the selection of native and/or synthetic polymers, three-dimensional scaffold fabrication, stem cell transplantation, and stem cell homing. A tooth is a complex biological organ. Tooth loss represents the most common organ failure. Tooth regeneration encompasses not only regrowth of an entire tooth as an organ, but also biological restoration of individual components of the tooth including enamel, dentin, cementum, or dental pulp. Regeneration of tooth root represents perhaps more near-term opportunities than the regeneration of the whole tooth. In the adult, a tooth owes its biological vitality, arguably more, to the root than the crown. Biomaterials are indispensible for the regeneration of tooth root, tooth crown, dental pulp, or an entire tooth.

  16. Elastin as a nonthrombogenic biomaterial. (United States)

    Waterhouse, Anna; Wise, Steven G; Ng, Martin K C; Weiss, Anthony S


    Surface-induced thrombosis is a significant issue for artificial blood-contacting materials used in the treatment of cardiovascular diseases. The development of biomaterials and tissue-engineered constructs that mimic the vasculature represents a way to overcome this problem. Elastin is an extracellular matrix macromolecule that imparts arterial elasticity where it comprises up to 50% of the nonhydrated mass of the vessel. In addition to its critical role in maintaining vessel integrity and elastic properties under pulsatile flow, elastin plays an important role in signaling and regulating luminal endothelial cells and smooth muscle cells in the arterial wall. Despite its well-established significance in the vasculature and its growing use as a biomaterial in tissue engineering, the hemocompatibility of elastin is often overlooked. Past studies pointing to the potential of arterial elastin and decellularized elastin as nonthrombogenic materials have begun to be realized, with elastin scaffolds and coatings displaying increased hemocomptibility. This review explores the mechanisms of elastin's nonthrombogenicity and highlights the current problems limiting its wider application as a biomaterial. We discuss the benefits of constructing biomaterials encompassing the relevant mechanical and biological features of elastin to provide enhanced hemocompatibility to biomaterials.

  17. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)


    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  18. What Types of Visual Recognition Tasks Are Mediated by the Neural Subsystem that Subserves Face Recognition? (United States)

    Brooks, Brian E.; Cooper, Eric E.


    Three divided visual field experiments tested current hypotheses about the types of visual shape representation tasks that recruit the cognitive and neural mechanisms underlying face recognition. Experiment 1 found a right hemisphere advantage for subordinate but not basic-level face recognition. Experiment 2 found a right hemisphere advantage for…

  19. Neural systems and hormones mediating attraction to infant and child faces. (United States)

    Luo, Lizhu; Ma, Xiaole; Zheng, Xiaoxiao; Zhao, Weihua; Xu, Lei; Becker, Benjamin; Kendrick, Keith M


    We find infant faces highly attractive as a result of specific features which Konrad Lorenz termed "Kindchenschema" or "baby schema," and this is considered to be an important adaptive trait for promoting protective and caregiving behaviors in adults, thereby increasing the chances of infant survival. This review first examines the behavioral support for this effect and physical and behavioral factors which can influence it. It then provides details of the increasing number of neuroimaging and electrophysiological studies investigating the neural circuitry underlying this baby schema effect in parents and non-parents of both sexes. Next it considers potential hormonal contributions to the baby schema effect in both sexes and the neural effects associated with reduced responses to infant cues in post-partum depression, anxiety and drug taking. Overall the findings reviewed reveal a very extensive neural circuitry involved in our perception of cuteness in infant faces, with enhanced activation compared to adult faces being found in brain regions involved in face perception, attention, emotion, empathy, memory, reward and attachment, theory of mind and also control of motor responses. Both mothers and fathers also show evidence for enhanced responses in these same neural systems when viewing their own as opposed to another child. Furthermore, responses to infant cues in many of these neural systems are reduced in mothers with post-partum depression or anxiety or have taken addictive drugs throughout pregnancy. In general reproductively active women tend to rate infant faces as cuter than men, which may reflect both heightened attention to relevant cues and a stronger activation in their brain reward circuitry. Perception of infant cuteness may also be influenced by reproductive hormones with the hypothalamic neuropeptide oxytocin being most strongly associated to date with increased attention and attraction to infant cues in both sexes.

  20. Neural systems and hormones mediating attraction to infant and child faces

    Directory of Open Access Journals (Sweden)

    Lizhu eLuo


    Full Text Available We find infant faces highly attractive as a result of specific features which Konrad Lorenz termed Kindchenschema or baby schema, and this is considered to be an important adaptive trait for promoting protective and caregiving behaviors in adults, thereby increasing the chances of infant survival. This review first examines the behavioral support for this effect and physical and behavioral factors which can influence it. It next reviews the increasing number of neuroimaging and electrophysiological studies investigating the neural circuitry underlying this baby schema effect in both parents and non-parents of both sexes. Next it considers potential hormonal contributions to the baby schema effect in both sexes and then neural effects associated with reduced responses to infant cues in post-partum depression, anxiety and drug taking. Overall the findings reviewed reveal a very extensive neural circuitry involved in our perception of cutenessin infant faces with enhanced activation compared to adult faces being found in brain regions involved in face perception, attention, emotion, empathy, memory, reward and attachment, theory of mind and also control of motor responses.Both mothers and fathers also show evidence for enhanced responses in these same neural systems when viewing their own as opposed to another child. Furthermore, responses to infant cues in many of these neural systems are reduced in mothers with post-partum depression or anxiety or have taken addictive drugs throughout pregnancy. In general reproductively active women tend to rate infant faces as cuter than men, which may reflect both heightened attention to relevant cues and a stronger activation in their brain reward circuitry. Perception of infant cuteness may also be influenced by reproductive hormones with the hypothalamic neuropeptide oxytocin being most strongly associated to date with increased attention andattractionto infant cues in both sexes.

  1. Chitin fulfilling a biomaterials promise

    CERN Document Server

    Khor, Eugene


    The second edition of Chitin underscores the important factors for standardizing chitin processing and characterization. It captures the essential interplay between chitin's assets and limitations as a biomaterial, placing the past promises of chitin in perspective, addressing its present realities and offering insight into what is required to realize chitin's destiny (including its derivative, chitosan) as a biomaterial of the twenty-first century. This book is an ideal guide for both industrialists and researchers with a vested interest in commercializing chitin.An upd

  2. 3D Biomaterial Microarrays for Regenerative Medicine

    DEFF Research Database (Denmark)

    Gaharwar, Akhilesh K.; Arpanaei, Ayyoob; Andresen, Thomas Lars;


    Three dimensional (3D) biomaterial microarrays hold enormous promise for regenerative medicine because of their ability to accelerate the design and fabrication of biomimetic materials. Such tissue-like biomaterials can provide an appropriate microenvironment for stimulating and controlling stem...

  3. Diverse ETS transcription factors mediate FGF signaling in the Ciona anterior neural plate. (United States)

    Gainous, T Blair; Wagner, Eileen; Levine, Michael


    The ascidian Ciona intestinalis is a marine invertebrate belonging to the sister group of the vertebrates, the tunicates. Its compact genome and simple, experimentally tractable embryos make Ciona well-suited for the study of cell-fate specification in chordates. Tunicate larvae possess a characteristic chordate body plan, and many developmental pathways are conserved between tunicates and vertebrates. Previous studies have shown that FGF signals are essential for neural induction and patterning at sequential steps of Ciona embryogenesis. Here we show that two different ETS family transcription factors, Ets1/2 and Elk1/3/4, have partially redundant activities in the anterior neural plate of gastrulating embryos. Whereas Ets1/2 promotes pigment cell formation in lateral lineages, both Ets1/2 and Elk1/3/4 are involved in the activation of Myt1L in medial lineages and the restriction of Six3/6 expression to the anterior-most regions of the neural tube. We also provide evidence that photoreceptor cells arise from posterior regions of the presumptive sensory vesicle, and do not depend on FGF signaling. Cells previously identified as photoreceptor progenitors instead form ependymal cells and neurons of the larval brain. Our results extend recent findings on FGF-dependent patterning of anterior-posterior compartments in the Ciona central nervous system.

  4. An adverse outcome pathway framework for neural tube and axial defects mediated by modulation of retinoic acid homeostasis. (United States)

    Tonk, Elisa C M; Pennings, Jeroen L A; Piersma, Aldert H


    Developmental toxicity can be caused through a multitude of mechanisms and can therefore not be captured through a single simple mechanistic paradigm. However, it may be possible to define a selected group of overarching mechanisms that might allow detection of the vast majority of developmental toxicants. Against this background, we have explored the usefulness of retinoic acid mediated regulation of neural tube and axial patterning as a general mechanism that, when perturbed, may result in manifestations of developmental toxicity that may cover a large part of malformations known to occur in experimental animals and in man. Through a literature survey, we have identified key genes in the regulation of retinoic acid homeostasis, as well as marker genes of neural tube and axial patterning, that may be used to detect developmental toxicants in in vitro systems. A retinoic acid-neural tube/axial patterning adverse outcome pathway (RA-NTA AOP) framework was designed. The framework was tested against existing data of flusilazole exposure in the rat whole embryo culture, the zebrafish embryotoxicity test, and the embryonic stem cell test. Flusilazole is known to interact with retinoic acid homeostasis, and induced common and unique NTA marker gene changes in the three test systems. Flusilazole-induced changes were similar in directionality to gene expression responses after retinoic acid exposure. It is suggested that the RA-NTA framework may provide a general tool to define mechanistic pathways and biomarkers of developmental toxicity that may be used in alternative in vitro assays for the detection of embryotoxic compounds.

  5. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  6. Integrated Biomaterials for Biomedical Technology

    CERN Document Server

    Ramalingam, Murugan; Ramakrishna, Seeram; Kobayashi, Hisatoshi


    This cutting edge book provides all the important aspects dealing with the basic science involved in materials in biomedical technology, especially structure and properties, techniques and technological innovations in material processing and characterizations, as well as the applications. The volume consists of 12 chapters written by acknowledged experts of the biomaterials field and covers a wide range of topics and applications.

  7. Predoctoral Curriculum Guidelines for Biomaterials. (United States)

    Journal of Dental Education, 1986


    The American Association of Dental Schools' predoctoral guidelines for biomaterials curricula includes notes on interrelationships between this and other fields, a curriculum overview, primary educational goals, prerequisites, a core content outline, specific behavioral objectives for each content area, and information on sequencing, faculty and…

  8. Inorganic biomaterials structure, properties and applications

    CERN Document Server

    Zhang, Xiang C


    This book provides a practical guide to the use and applications of inorganic biomaterials. It begins by introducing the concept of inorganic biomaterials, which includes bioceramics and bioglass. This concept is further extended to hybrid biomaterials consisting of inorganic and organic materials to mimic natural biomaterials. The book goes on to provide the reader with information on biocompatibility, bioactivity and bioresorbability. The concept of the latter is important because of the increasing role resorbable biomaterials are playing in implant applications. The book also introduces a n

  9. Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh


    Full Text Available All biomaterials, when implanted in vivo, elicit cellular and tissue responses. These responses include the inflammatory and wound healing responses, foreign body reactions, and fibrous encapsulation of the implanted materials. Macrophages are myeloid immune cells that are tactically situated throughout the tissues, where they ingest and degrade dead cells and foreign materials in addition to orchestrating inflammatory processes. Macrophages and their fused morphologic variants, the multinucleated giant cells, which include the foreign body giant cells (FBGCs are the dominant early responders to biomaterial implantation and remain at biomaterial-tissue interfaces for the lifetime of the device. An essential aspect of macrophage function in the body is to mediate degradation of bio-resorbable materials including bone through extracellular degradation and phagocytosis. Biomaterial surface properties play a crucial role in modulating the foreign body reaction in the first couple of weeks following implantation. The foreign body reaction may impact biocompatibility of implantation devices and may considerably impact short- and long-term success in tissue engineering and regenerative medicine, necessitating a clear understanding of the foreign body reaction to different implantation materials. The focus of this review article is on the interactions of macrophages and foreign body giant cells with biomaterial surfaces, and the physical, chemical and morphological characteristics of biomaterial surfaces that play a role in regulating the foreign body response. Events in the foreign body response include protein adsorption, adhesion of monocytes/macrophages, fusion to form FBGCs, and the consequent modification of the biomaterial surface. The effect of physico-chemical cues on macrophages is not well known and there is a complex interplay between biomaterial properties and those that result from interactions with the local environment. By having a

  10. AgRP Neural Circuits Mediate Adaptive Behaviors in the Starved State (United States)

    Padilla, Stephanie L.; Qiu, Jian; Soden, Marta E.; Sanz, Elisenda; Nestor, Casey C; Barker, Forrest D.; Quintana, Albert; Zweifel, Larry S.; Rønnekleiv, Oline K.; Kelly, Martin J.; Palmiter, Richard D.


    In the face of starvation animals will engage in high-risk behaviors that would normally be considered maladaptive. Starving rodents for example will forage in areas that are more susceptible to predators and will also modulate aggressive behavior within a territory of limited or depleted nutrients. The neural basis of these adaptive behaviors likely involves circuits that link innate feeding, aggression, and fear. Hypothalamic AgRP neurons are critically important for driving feeding and project axons to brain regions implicated in aggression and fear. Using circuit-mapping techniques, we define a disynaptic network originating from a subset of AgRP neurons that project to the medial nucleus of the amygdala and then to the principle bed nucleus of the stria terminalis, which plays a role in suppressing territorial aggression and reducing contextual fear. We propose that AgRP neurons serve as a master switch capable of coordinating behavioral decisions relative to internal state and environmental cues. PMID:27019015

  11. A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

    Directory of Open Access Journals (Sweden)

    Salvatore Fusco


    Full Text Available Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis.

  12. Sensory control and organization of neural networks mediating coordination of multisegmental organs for locomotion. (United States)

    Büschges, Ansgar


    It is well established that locomotor patterns result from the interaction between central pattern generating networks in the nervous system, local feedback from sensory neurons about movements and forces generated in the locomotor organs, and coordinating signals from neighboring segments or appendages. This review addresses the issue of how the movements of multi-segmented locomotor organs are coordinated and provides an overview of recent advances in understanding sensory control and the internal organization of central pattern generating networks that operate multi-segmented locomotor organs, such as a walking leg. Findings from the stick insect and the cat are compared and discussed in relation to new findings on the lamprey swimming network. These findings support the notion that common schemes of sensory feedback are used for generating walking and that central neural networks controlling multi-segmented locomotor organs generally encompass multiple central pattern generating networks that correspond with the segmental structure of the locomotor organ.

  13. The neural mediators of kindness-based meditation: a theoretical model

    Directory of Open Access Journals (Sweden)

    Jennifer Streiffer Mascaro


    Full Text Available Although kindness-based contemplative practices are increasingly employed by clinicians and cognitive researchers to enhance prosocial emotions, social cognitive skills, and well-being, and as a tool to understand the basic workings of the social mind, we lack a coherent theoretical model with which to test the mechanisms by which kindness-based meditation may alter the brain and body. Here we link contemplative accounts of compassion and loving-kindness practices with research from social cognitive neuroscience and social psychology to generate predictions about how diverse practices may alter brain structure and function and related aspects of social cognition. Contingent on the nuances of the practice, kindness-based meditation may enhance the neural systems related to faster and more basic perceptual or motor simulation processes, simulation of another’s affective body state, slower and higher-level perspective-taking, modulatory processes such as emotion regulation and self/other discrimination, and combinations thereof. This theoretical model will be discussed alongside best practices for testing such a model and potential implications and applications of future work.

  14. Serotonergic neurons mediate dyskinesia side effects in Parkinson's patients with neural transplants. (United States)

    Politis, Marios; Wu, Kit; Loane, Clare; Quinn, Niall P; Brooks, David J; Rehncrona, Stig; Bjorklund, Anders; Lindvall, Olle; Piccini, Paola


    Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by l-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT(1A)) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.

  15. Curiosity and Cure: Translational Research Strategies for Neural Repair-Mediated Rehabilitation (United States)

    Dobkin, Bruce H.


    Clinicians who seek interventions for neural repair in patients with paralysis and other impairments may extrapolate the results of cell culture and rodent experiments into the framework of a preclinical study. These experiments, however, must be interpreted within the context of the model and the highly constrained hypothesis and manipulation being tested. Rodent models of repair for stroke and spinal cord injury offer examples of potential pitfalls in the interpretation of results from developmental gene activation, transgenic mice, endogeneous neurogenesis, cellular transplantation, axon regeneration and remyelination, dendritic proliferation, activity-dependent adaptations, skills learning, and behavioral testing. Preclinical experiments that inform the design of human trials ideally include a lesion of etiology, volume and location that reflects the human disease; examine changes induced by injury and by repair procedures both near and remote from the lesion; distinguish between reactive molecular and histologic changes versus changes critical to repair cascades; employ explicit training paradigms for the reacquisition of testable skills; correlate morphologic and physiologic measures of repair with behavioral measures of task reacquisition; reproduce key results in more than one laboratory, in different strains or species of rodent, and in a larger mammal; and generalize the results across several disease models, such as axonal regeneration in a stroke and spinal cord injury platform. Collaborations between basic and clinical scientists in the development of translational animal models of injury and repair can propel experiments for ethical bench-to-bedside therapies to augment the rehabilitation of disabled patients. PMID:17514711

  16. Sex differences in the neural mechanisms mediating addiction: a new synthesis and hypothesis

    Directory of Open Access Journals (Sweden)

    Becker Jill B


    Full Text Available Abstract In this review we propose that there are sex differences in how men and women enter onto the path that can lead to addiction. Males are more likely than females to engage in risky behaviors that include experimenting with drugs of abuse, and in susceptible individuals, they are drawn into the spiral that can eventually lead to addiction. Women and girls are more likely to begin taking drugs as self-medication to reduce stress or alleviate depression. For this reason women enter into the downward spiral further along the path to addiction, and so transition to addiction more rapidly. We propose that this sex difference is due, at least in part, to sex differences in the organization of the neural systems responsible for motivation and addiction. Additionally, we suggest that sex differences in these systems and their functioning are accentuated with addiction. In the current review we discuss historical, cultural, social and biological bases for sex differences in addiction with an emphasis on sex differences in the neurotransmitter systems that are implicated.

  17. Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors (United States)

    Sellgren, C M; Sheridan, S D; Gracias, J; Xuan, D; Fu, T; Perlis, R H


    Engulfment of synapses and neural progenitor cells (NPCs) by microglia is critical for the development and maintenance of proper brain circuitry, and has been implicated in neurodevelopmental as well as neurodegenerative disease etiology. We have developed and validated models of these mechanisms by reprogramming microglia-like cells from peripheral blood mononuclear cells, and combining them with NPCs and neurons derived from induced pluripotent stem cells to create patient-specific cellular models of complement-dependent synaptic pruning and elimination of NPCs. The resulting microglia-like cells express appropriate markers and function as primary human microglia, while patient-matched macrophages differ markedly. As a demonstration of disease-relevant application, we studied the role of C4, recently implicated in schizophrenia, in engulfment of synaptic structures by human microglia. The ability to create complete patient-specific cellular models of critical microglial functions utilizing samples taken during a single clinical visit will extend the ability to model central nervous system disease while facilitating high-throughput screening. PMID:27956744

  18. Conductive polymers: towards a smart biomaterial for tissue engineering. (United States)

    Balint, Richard; Cassidy, Nigel J; Cartmell, Sarah H


    Developing stimulus-responsive biomaterials with easy-to-tailor properties is a highly desired goal of the tissue engineering community. A novel type of electroactive biomaterial, the conductive polymer, promises to become one such material. Conductive polymers are already used in fuel cells, computer displays and microsurgical tools, and are now finding applications in the field of biomaterials. These versatile polymers can be synthesised alone, as hydrogels, combined into composites or electrospun into microfibres. They can be created to be biocompatible and biodegradable. Their physical properties can easily be optimized for a specific application through binding biologically important molecules into the polymer using one of the many available methods for their functionalization. Their conductive nature allows cells or tissue cultured upon them to be stimulated, the polymers' own physical properties to be influenced post-synthesis and the drugs bound in them released, through the application of an electrical signal. It is thus little wonder that these polymers are becoming very important materials for biosensors, neural implants, drug delivery devices and tissue engineering scaffolds. Focusing mainly on polypyrrole, polyaniline and poly(3,4-ethylenedioxythiophene), we review conductive polymers from the perspective of tissue engineering. The basic properties of conductive polymers, their chemical and electrochemical synthesis, the phenomena underlying their conductivity and the ways to tailor their properties (functionalization, composites, etc.) are discussed.

  19. Engineering Biomaterial Properties for Central Nervous System Applications (United States)

    Rivet, Christopher John

    Biomaterials offer unique properties that are intrinsic to the chemistry of the material itself or occur as a result of the fabrication process; iron oxide nanoparticles are superparamagnetic, which enables controlled heating in the presence of an alternating magnetic field, and a hydrogel and electrospun fiber hybrid material provides minimally invasive placement of a fibrous, artificial extracellular matrix for tissue regeneration. Utilization of these unique properties towards central nervous system disease and dysfunction requires a thorough definition of the properties in concert with full biological assessment. This enables development of material-specific features to elicit unique cellular responses. Iron oxide nanoparticles are first investigated for material-dependent, cortical neuron cytotoxicity in vitro and subsequently evaluated for alternating magnetic field stimulation induced hyperthermia, emulating the clinical application for enhanced chemotherapy efficacy in glioblastoma treatment. A hydrogel and electrospun fiber hybrid material is first applied to a rat brain to evaluate biomaterial interface astrocyte accumulation as a function of hybrid material composition. The hybrid material is then utilized towards increasing functional engraftment of dopaminergic progenitor neural stem cells in a mouse model of Parkinson's disease. Taken together, these two scenarios display the role of material property characterization in development of biomaterial strategies for central nervous system repair and regeneration.

  20. A leg-local neural mechanism mediates the decision to search in stick insects. (United States)

    Berg, Eva M; Hooper, Scott L; Schmidt, Joachim; Büschges, Ansgar


    In many animals, individual legs can either function independently, as in behaviors such as scratching or searching, or be used in coordinated patterns with other legs, as in walking or climbing. While the control of walking has been extensively investigated, the mechanisms mediating the behavioral choice to activate individual legs independently are poorly understood. We examined this issue in stick insects, in which each leg can independently produce a rhythmic searching motor pattern if it doesn't find a foothold [1-4]. We show here that one non-spiking interneuron, I4, controls searching behavior in individual legs. One I4 is present in each hemi-segment of the three thoracic ganglia [5, 6]. Search-inducing sensory input depolarizes I4. I4 activity was necessary and sufficient to initiate and maintain searching movements. When substrate contact was provided, I4 depolarization no longer induced searching. I4 therefore both integrates search-inducing sensory input and is gated out by other sensory input (substrate contact). Searching thus occurs only when it is behaviorally appropriate. I4 depolarization never elicited stepping. These data show that individual, locally activated neurons can mediate the behavioral choice to use individual legs independently. This mechanism may be particularly important in insects' front legs, which can function independently like vertebrate arms and hands [7]. Similar local command mechanisms that selectively activate the pattern generators controlling repeated functional units such as legs or body segments may be present in other systems.

  1. Biomaterials in Canada: the first four decades. (United States)

    Brash, John L


    Biomaterials research in Canada began in the 1960s. Over the past four decades significant contributions have been made across a broad spectrum covering dental, orthopaedic, cardiovascular, neuro, and ocular biomaterials. Canadians have also been active in the derivative area of tissue engineering. Biomaterials laboratories are now established in universities and research institutes from coast to coast, supported mainly by funding from the Federal and Provincial Governments. The Canadian Biomaterials Society was formed in 1971 and has played an important role in the development of the field. The Society played host to the 5th World Biomaterials Congress in Toronto in 1996. The work of Canadian researchers over the past four decades is summarized briefly. It is concluded that biomaterials and tissue engineering is a mature, strong area of research in Canada and appears set to continue as such into the future.

  2. AKT signaling mediates IGF-I survival actions on otic neural progenitors.

    Directory of Open Access Journals (Sweden)

    Maria R Aburto

    Full Text Available BACKGROUND: Otic neurons and sensory cells derive from common progenitors whose transition into mature cells requires the coordination of cell survival, proliferation and differentiation programmes. Neurotrophic support and survival of post-mitotic otic neurons have been intensively studied, but the bases underlying the regulation of programmed cell death in immature proliferative otic neuroblasts remains poorly understood. The protein kinase AKT acts as a node, playing a critical role in controlling cell survival and cell cycle progression. AKT is activated by trophic factors, including insulin-like growth factor I (IGF-I, through the generation of the lipidic second messenger phosphatidylinositol 3-phosphate by phosphatidylinositol 3-kinase (PI3K. Here we have investigated the role of IGF-dependent activation of the PI3K-AKT pathway in maintenance of otic neuroblasts. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of organotypic cultures of chicken (Gallus gallus otic vesicles and acoustic-vestibular ganglia, Western blotting, immunohistochemistry and in situ hybridization, we show that IGF-I-activation of AKT protects neural progenitors from programmed cell death. IGF-I maintains otic neuroblasts in an undifferentiated and proliferative state, which is characterised by the upregulation of the forkhead box M1 (FoxM1 transcription factor. By contrast, our results indicate that post-mitotic p27(Kip-positive neurons become IGF-I independent as they extend their neuronal processes. Neurons gradually reduce their expression of the Igf1r, while they increase that of the neurotrophin receptor, TrkC. CONCLUSIONS/SIGNIFICANCE: Proliferative otic neuroblasts are dependent on the activation of the PI3K-AKT pathway by IGF-I for survival during the otic neuronal progenitor phase of early inner ear development.

  3. Biomaterials in Relation to Dentistry. (United States)

    Deb, Sanjukta; Chana, Simran


    Dental caries remains a challenge in the improvement of oral health. It is the most common and widespread biofilm-dependent oral disease, resulting in the destruction of tooth structure by the acidic attack from cariogenic bacteria. The tooth is a heavily mineralised tissue, and both enamel and dentine can undergo demineralisation due to trauma or dietary conditions. The adult population worldwide affected by dental caries is enormous and despite significant advances in caries prevention and tooth restoration, treatments continue to pose a substantial burden to healthcare. Biomaterials play a vital role in the restoration of the diseased or damaged tooth structure and, despite providing reasonable outcomes, there are some concerns with clinical performance. Amalgam, the silver grey biomaterial that has been widely used as a restorative material in dentistry, is currently in throes of being phased out, especially with the Minimata convention and treaty being signed by a number of countries (January 2013; that aims to control the anthropogenic release of mercury in the environment, which naturally impacts the use of amalgam, where mercury is a component. Thus, the development of alternative restoratives and restoration methods that are inexpensive, can be used under different climatic conditions, withstand storage and allow easy handling, the main prerequisites of dental biomaterials, is important. The potential for using biologically engineered tissue and consequent research to replace damaged tissues has also seen a quantum leap in the last decade. Ongoing research in regenerative treatments in dentistry includes alveolar ridge augmentation, bone tissue engineering and periodontal ligament replacement, and a future aim is bioengineering of the whole tooth. Research towards developing bioengineered teeth is well underway and identification of adult stem cell sources to make this a viable treatment is advancing; however, this

  4. Neural cell adhesion molecule-180-mediated homophilic binding induces epidermal growth factor receptor (EGFR) down-regulation and uncouples the inhibitory function of EGFR in neurite outgrowth

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Berezin, Vladimir; Bock, Elisabeth


    The neural cell adhesion molecule (NCAM) plays important roles in neuronal development, regeneration, and synaptic plasticity. NCAM homophilic binding mediates cell adhesion and induces intracellular signals, in which the fibroblast growth factor receptor plays a prominent role. Recent studies...... not require NCAM-mediated fibroblast growth factor receptor activation....... on axon guidance in Drosophila suggest that NCAM also regulates the epidermal growth factor receptor (EGFR) (Molecular and Cellular Neuroscience, 28, 2005, 141). A possible interaction between NCAM and EGFR in mammalian cells has not been investigated. The present study demonstrates for the first time...

  5. Biomaterials & scaffolds for tissue engineering

    Directory of Open Access Journals (Sweden)

    Fergal J. O'Brien


    Full Text Available Every day thousands of surgical procedures are performed to replace or repair tissue that has been damaged through disease or trauma. The developing field of tissue engineering (TE aims to regenerate damaged tissues by combining cells from the body with highly porous scaffold biomaterials, which act as templates for tissue regeneration, to guide the growth of new tissue. This article describes the functional requirements, and types, of materials used in developing state of the art of scaffolds for tissue engineering applications. Furthermore, it describes the challenges and where future research and direction is required in this rapidly advancing field.

  6. Mapping the neural systems that mediate the Paced Auditory Serial Addition Task (PASAT). (United States)

    Lockwood, Alan H; Linn, Richard T; Szymanski, Herman; Coad, Mary Lou; Wack, David S


    The paced auditory serial addition task (PASAT), in which subjects hear a number-string and add the two most-recently heard numbers, is a neuropsychological test sensitive to cerebral dysfunction. We mapped the brain regions activated by the PASAT using positron emission tomography (PET) and 15O-water to measure cerebral blood flow. We parsed the PASAT by mapping sites activated by immediate repetition of numbers and by repetition of the prior number after the presentation of the next number in the series. The PASAT activated dispersed non-contiguous foci in the superior temporal gyri, bifrontal and biparietal sites, the anterior cingulate and bilateral cerebellar sites. These sites are consistent with the elements of the task that include auditory perception and processing, speech production, working memory, and attention. Sites mediating addition were not identified. The extent of the sites activated during the performance of the PASAT accounts for the sensitivity of this test and justifies its use in a variety of seemingly disparate conditions.

  7. Ketamine, propofol and the EEG: a neural field analysis of HCN1-mediated interactions

    Directory of Open Access Journals (Sweden)

    Ingo eBojak


    Full Text Available Ketamine and propofol are two well-known, powerful anesthetic agents, yet at first sight this appears to be their only commonality. Ketamine is a dissociative anesthetic agent, whose main mechanism of action is considered to be N-methyl-D-aspartate (NMDA antagonism; whereas propofol is a general anesthetic agent, which is assumed to primarily potentiate currents gated by γ-aminobutyric acid type A (GABA A receptors. However, several experimental observations suggest a closer relationship. First, the effect of ketamine on the electroencephalogram (EEG is markedly changed in the presence of propofol: on its own ketamine increases theta (4–8 Hz and decreases alpha (8–13 Hz oscillations, whereas ketamine induces a significant shift to beta band frequencies (13–30 Hz in the presence of propofol. Second, both ketamine and propofol cause inhibition of the inward pacemaker current Ih, by binding to the corresponding hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1 subunit. The resulting effect is a hyperpolarization of the neuron’s resting membrane potential. Third, the ability of both ketamine and propofol to induce hypnosis is reduced in HCN1-knockout mice. Here we show that one can theoretically understand the observed spectral changes of the EEG based on HCN1-mediated hyperpolarizations alone, without involving the supposed main mechanisms of action of these drugs through NMDA and GABA A, respectively. On the basis of our successful EEG model we conclude that ketamine and propofol should be antagonistic to each other in their interaction at HCN1 subunits. Such a prediction is in accord with the results of clinical experiment in which it is found that ketamine and propofol interact in an infra-additive manner with respect to the endpoints of hypnosis and immobility.

  8. Neural evidence for competition-mediated suppression in the perception of a single object. (United States)

    Cacciamani, Laura; Scalf, Paige E; Peterson, Mary A


    Multiple objects compete for representation in visual cortex. Competition may also underlie the perception of a single object. Computational models implement object perception as competition between units on opposite sides of a border. The border is assigned to the winning side, which is perceived as an object (or "figure"), whereas the other side is perceived as a shapeless ground. Behavioral experiments suggest that the ground is inhibited to a degree that depends on the extent to which it competed for object status, and that this inhibition is relayed to low-level brain areas. Here, we used fMRI to assess activation for ground regions of task-irrelevant novel silhouettes presented in the left or right visual field (LVF or RVF) while participants performed a difficult task at fixation. Silhouettes were designed so that the insides would win the competition for object status. The outsides (grounds) suggested portions of familiar objects in half of the silhouettes and novel objects in the other half. Because matches to object memories affect the competition, these two types of silhouettes operationalized, respectively, high competition and low competition from the grounds. The results showed that activation corresponding to ground regions was reduced for high- versus low-competition silhouettes in V4, where receptive fields (RFs) are large enough to encompass the familiar objects in the grounds, and in V1/V2, where RFs are much smaller. These results support a theory of object perception involving competition-mediated ground suppression and feedback from higher to lower levels. This pattern of results was observed in the left hemisphere (RVF), but not in the right hemisphere (LVF). One explanation of the lateralized findings is that task-irrelevant silhouettes in the RVF captured attention, allowing us to observe these effects, whereas those in the LVF did not. Experiment 2 provided preliminary behavioral evidence consistent with this possibility.

  9. Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons.

    Directory of Open Access Journals (Sweden)

    Takahiro Ishimoto

    Full Text Available The aim of the present study is to clarify the functional expression and physiological role in neural progenitor cells (NPCs of carnitine/organic cation transporter OCTN1/SLC22A4, which accepts the naturally occurring food-derived antioxidant ergothioneine (ERGO as a substrate in vivo. Real-time PCR analysis revealed that mRNA expression of OCTN1 was much higher than that of other organic cation transporters in mouse cultured cortical NPCs. Immunocytochemical analysis showed colocalization of OCTN1 with the NPC marker nestin in cultured NPCs and mouse embryonic carcinoma P19 cells differentiated into neural progenitor-like cells (P19-NPCs. These cells exhibited time-dependent [(3H]ERGO uptake. These results demonstrate that OCTN1 is functionally expressed in murine NPCs. Cultured NPCs and P19-NPCs formed neurospheres from clusters of proliferating cells in a culture time-dependent manner. Exposure of cultured NPCs to ERGO or other antioxidants (edaravone and ascorbic acid led to a significant decrease in the area of neurospheres with concomitant elimination of intracellular reactive oxygen species. Transfection of P19-NPCs with small interfering RNA for OCTN1 markedly promoted formation of neurospheres with a concomitant decrease of [(3H]ERGO uptake. On the other hand, exposure of cultured NPCs to ERGO markedly increased the number of cells immunoreactive for the neuronal marker βIII-tubulin, but decreased the number immunoreactive for the astroglial marker glial fibrillary acidic protein (GFAP, with concomitant up-regulation of neuronal differentiation activator gene Math1. Interestingly, edaravone and ascorbic acid did not affect such differentiation of NPCs, in contrast to the case of proliferation. Knockdown of OCTN1 increased the number of cells immunoreactive for GFAP, but decreased the number immunoreactive for βIII-tubulin, with concomitant down-regulation of Math1 in P19-NPCs. Thus, OCTN1-mediated uptake of ERGO in NPCs inhibits

  10. Permeability testing of biomaterial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Dreesmann, L; Hajosch, R; Nuernberger, J Vaz; Schlosshauer, B [NMI Natural and Medical Sciences Institute at University Tuebingen, Markwiesenstr. 55, D-72770 Reutlingen (Germany); Ahlers, M [GELITA AG, Gammelsbacher Str. 2, D-69412 Eberbach (Germany)], E-mail:


    The permeability characteristics of biomaterials are critical parameters for a variety of implants. To analyse the permeability of membranes made from crosslinked ultrathin gelatin membranes and the transmigration of cells across the membranes, we combined three technical approaches: (1) a two-chamber-based permeability assay, (2) cell culturing with cytochemical analysis and (3) biochemical enzyme electrophoresis (zymography). Based on the diffusion of a coloured marker molecule in conjunction with photometric quantification, permeability data for a gelatin membrane were determined in the presence or absence of gelatin degrading fibroblasts. Cytochemical evaluation after cryosectioning of the membranes was used to ascertain whether fibroblasts had infiltrated the membrane inside. Zymography was used to investigate the potential release of proteases from fibroblasts, which are known to degrade collagen derivatives such as gelatin. Our data show that the diffusion equilibrium of a low molecular weight dye across the selected gelatin membrane is approached after about 6-8 h. Fibroblasts increase the permeability due to cavity formation in the membrane inside without penetrating the membrane for an extended time period (>21 days in vitro). Zymography indicates that cavity formation is most likely due to the secretion of matrix metalloproteinases. In summary, the combination of the depicted methods promises to facilitate a more rational development of biomaterials, because it provides a rapid means of determining permeability characteristics and bridges the gap between descriptive methodology and the mechanistic understanding of permeability alterations due to biological degradation.

  11. Current requirements for polymeric biomaterials in otolaryngology

    Directory of Open Access Journals (Sweden)

    Sternberg, Katrin


    Full Text Available In recent years otolaryngology was strongly influenced by newly developed implants which are based on both, innovative biomaterials and novel implant technologies. Since the biomaterials are integrated into biological systems they have to fulfill all technical requirements and accommodate biological interactions. Technical functionality relating to implant specific mechanical properties, a sufficiently high stability in terms of physiological conditions, and good biocompatibility are the demands with regard to suitability of biomaterials. The goal in applying biomaterials for implants is to maintain biofunctionality over extended periods of time. These general demands to biomaterials are equally valid for use in otolaryngology. Different classes of materials can be utilized as biomaterials. Metals belong to the oldest biomaterials. In addition, alloys, ceramics, inorganic glasses and composites have been tested successfully. Furthermore, natural and synthetic polymers are widely used materials, which will be in the focus of the current article with regard to their properties and usage as cochlear implants, osteosynthesis implants, stents, and matrices for tissue engineering. Due to their application as permanent or temporary implants materials are differentiated into biostable and biodegradable polymers. The here identified general and up to date requirements for biomaterials and the illustrated applications in otolaryngology emphasize ongoing research efforts in this area and at the same time demonstrate the high significance of interdisciplinary cooperation between natural sciences, engineering, and medical sciences.

  12. Compatibility of embryonic stem cells with biomaterials. (United States)

    Handschel, Jörg; Berr, Karin; Depprich, Rita; Naujoks, Christian; Kübler, Norbert R; Meyer, Ulrich; Ommerborn, Michelle; Lammers, Lydia


    Periodontal bone defects and atrophy of the jaws in an aging population are of special concern. Tissue engineering using embryonic stem cells (ESCs) and biomaterials may offer new therapeutic options. The purpose of this study is to evaluate the compatibility of ESCs with biomaterials and the influence of biomaterials on the osteogenic gene expression profile.Therefore, ESCs are cultured with various biomaterials. The cytocompatibility of murine ESCs is measured regarding the proliferation of the cells on the materials by CyQUANT assay, the morphology by scanning electron microscopy, and the influence on the gene expression by real time PCR.The results show that insoluble collagenous bone matrix, followed by beta-tricalciumphosphate, is most suitable for bone tissue engineering regarding cell proliferation, and phenotype. The gene expression analysis indicates that biomaterials do influence the gene expression of ESCs.Our results provide new insight into the cytocompatibility of ESCs on different scaffolds.

  13. Advanced biomaterials for repairing the nervous system: what can hydrogels do for the brain?

    Directory of Open Access Journals (Sweden)

    Zin Z. Khaing


    Full Text Available Newly developed hydrogels are likely to play significant roles in future therapeutic strategies for the nervous system. In this review, unique features of the central nervous system (i.e., the brain and spinal cord that are important to consider in developing engineered biomaterials for therapeutic applications are discussed. This review focuses on recent findings in hydrogels as biomaterials for use as (1 drug delivery devices, specifically focusing on how the material can change the delivery rate of small molecules, (2 scaffolds that can modify the post-injury environment, including preformed and injectable scaffolds, (3 cell delivery vehicles, discussing cellular response to natural and synthetic polymers as well as structured and amorphous materials, and (4 scaffolds for tissue regeneration, describing micro- and macro-architectural constructs that have been designed for neural applications. In addition, key features in each category that are likely to contribute to the translational success of these biomaterials are highlighted.

  14. Biomaterial science meets computational biology. (United States)

    Hutmacher, Dietmar W; Little, J Paige; Pettet, Graeme J; Loessner, Daniela


    There is a pressing need for a predictive tool capable of revealing a holistic understanding of fundamental elements in the normal and pathological cell physiology of organoids in order to decipher the mechanoresponse of cells. Therefore, the integration of a systems bioengineering approach into a validated mathematical model is necessary to develop a new simulation tool. This tool can only be innovative by combining biomaterials science with computational biology. Systems-level and multi-scale experimental data are incorporated into a single framework, thus representing both single cells and collective cell behaviour. Such a computational platform needs to be validated in order to discover key mechano-biological factors associated with cell-cell and cell-niche interactions.

  15. New biomaterials for orthopedic implants

    Directory of Open Access Journals (Sweden)

    Ong KL


    Full Text Available Kevin L Ong, Brian Min Yun, Joshua B WhiteExponent, Inc., Philadelphia, PA, USAAbstract: With the increasing use of orthopedic implants worldwide, there continues to be great interest in the development of novel technologies to further improve the effective clinical performance of contemporary treatment modalities and devices. Continuing research interest also exists in developing novel bulk biomaterials (eg, polycarbonate urethanes, silicon or novel formulations of existing but less widely used biomaterials (eg, polyaryletherketones, polyetheretherketone. There is also growing focus on customizing the material properties of bioabsorbables and composite materials with fillers such as bioactive ceramics. In terms of tissue engineering, more recent developments have focused on basic engineering and biological fundamentals to use cells, signaling factors, and the scaffold material itself to better restore tissue and organ structure and function. There has also been recent controversy with the use of injectables as a nonsurgical approach to treat joint disorders, but more attention is being directed toward the development of newer formulations with different molecular weights. The industry has also continuously sought to improve coatings to supplement the function of existing implants, with the goal of improving their osseointegrative qualities and incorporating antimicrobial properties. These include the use of bone morphogenetic protein, bisphosphonates, calcium phosphate, silicon nitride, and iodine. Due to the widespread use of bone graft materials, recent developments in synthetic graft materials have explored further development of bioactive glass, ceramic materials, and porous titanium particles. This review article provides an overview of ongoing efforts in the above research areas.Keywords: coatings, scaffolds, bioabsorbables, bone graft, injectables

  16. Biomaterials and Stem Cells in Regenerative Medicine

    CERN Document Server

    Ramalingam, Murugan; Best, Serena


    Work in the area of biomaterials and stem cell therapy has revealed great potential for many applications, from the treatment of localized defects and diseases to the repair and replacement of whole organs. Researchers have also begun to develop a better understanding of the cellular environment needed for optimal tissue repair and regeneration. Biomaterials and Stem Cells in Regenerative Medicine explores a range of applications for biomaterials and stem cell therapy and describes recent research on suitable cell scaffolds and substrates for tissue repair and reconstruction. Featuring contrib

  17. Polymeric biomaterials structure and function, v.1

    CERN Document Server

    Dumitriu, Severian


    Biomaterials have had a major impact on the practice of contemporary medicine and patient care. Growing into a major interdisciplinary effort involving chemists, biologists, engineers, and physicians, biomaterials development has enabled the creation of high-quality devices, implants, and drug carriers with greater biocompatibility and biofunctionality. The fast-paced research and increasing interest in finding new and improved biocompatible or biodegradable polymers has provided a wealth of new information, transforming this edition of Polymeric Biomaterials into a two-volume set. This volume

  18. Tribological applications of biomaterials: an overview

    Institute of Scientific and Technical Information of China (English)


    Tribological research is the study of lubrication, friction, and wear. Tribology of biomate-rials is to study how the materials work and fail. This will help us to produce better biomaterials.Tribology plays a very important role in improving the design and making successful biomaterialsfor medical purposes. Joints of human body, such as hip, knee, jaw, dental parts etc., all need toconsider the wear and lubrication problem. In this paper, we give a general introduction of bioma-terial research in tribological applications. Materials, the synthetic characterization, and their failureare introduced.

  19. Electrical stimulation of neural stem cells mediated by humanized carbon nanotube composite made with extracellular matrix protein. (United States)

    Kam, Nadine Wong Shi; Jan, Edward; Kotov, Nicholas A


    One of the key challenges to engineering neural interfaces is to minimize their immune response toward implanted electrodes. One potential approach is to manufacture materials that bear greater structural resemblance to living tissues and by utilizing neural stem cells. The unique electrical and mechanical properties of carbon nanotubes make them excellent candidates for neural interfaces, but their adoption hinges on finding approaches for "humanizing" their composites. Here we demonstrated the fabrication of layer-by-layer assembled composites from single-walled carbon nanotubes (SWNTs) and laminin, which is an essential part of human extracellular matrix. Laminin-SWNT thin films were found to be conducive to neural stem cells (NSC) differentiation and suitable for their successful excitation. We observed extensive formation of functional neural network as indicated by the presence of synaptic connections. Calcium imaging of the NSCs revealed generation of action potentials upon the application of a lateral current through the SWNT substrate. These results indicate that the protein-SWNT composite can serve as materials foundation of neural electrodes with chemical structure better adapted with long-term integration with the neural tissue.

  20. Dental biomaterials: where are we and where are we going? (United States)

    Bayne, Stephen C


    This article reviews the current state of the art for restorative biomaterials by examining the roles of 1) truly biological biomaterials, with respect to the "near-future" of five to ten years, 2) traditional synthetic biomaterials, and 3) performance outcomes for biomaterials. Biological biomaterials are discussed in terms of tissue engineering and stem cell research, self-assembling system opportunities, and nanotechniques or technologies. Future developments for major areas of synthetic biomaterials are considered for bonding systems, composites, VLC curing, ceramics, and cements. Performance outcomes are discussed for all biomaterials in terms of safety, efficacy, and longevity of materials.

  1. Designing Biomaterials for 3D Printing. (United States)

    Guvendiren, Murat; Molde, Joseph; Soares, Rosane M D; Kohn, Joachim


    Three-dimensional (3D) printing is becoming an increasingly common technique to fabricate scaffolds and devices for tissue engineering applications. This is due to the potential of 3D printing to provide patient-specific designs, high structural complexity, rapid on-demand fabrication at a low-cost. One of the major bottlenecks that limits the widespread acceptance of 3D printing in biomanufacturing is the lack of diversity in "biomaterial inks". Printability of a biomaterial is determined by the printing technique. Although a wide range of biomaterial inks including polymers, ceramics, hydrogels and composites have been developed, the field is still struggling with processing of these materials into self-supporting devices with tunable mechanics, degradation, and bioactivity. This review aims to highlight the past and recent advances in biomaterial ink development and design considerations moving forward. A brief overview of 3D printing technologies focusing on ink design parameters is also included.

  2. Biomaterials in the repair of sports injuries (United States)

    Ducheyne, Paul; Mauck, Robert L.; Smith, Douglas H.


    The optimal stimulation of tissue regeneration in bone, cartilage and spinal cord injuries involves a judicious selection of biomaterials with tailored chemical compositions, micro- and nanostructures, porosities and kinetic release properties for the delivery of relevant biologically active molecules.

  3. Ceramics as biomaterials for dental restoration. (United States)

    Höland, Wolfram; Schweiger, Marcel; Watzke, Ronny; Peschke, Arnd; Kappert, Heinrich


    Sintered ceramics and glass-ceramics are widely used as biomaterials for dental restoration, especially as dental inlays, onlays, veneers, crowns or bridges. Biomaterials were developed either to veneer metal frameworks or to produce metal-free dental restorations. Different types of glass-ceramics and ceramics are available and necessary today to fulfill customers' needs (patients, dentists and dental technicians) regarding the properties of the biomaterials and the processing of the products. All of these different types of biomaterials already cover the entire range of indications of dental restorations. Today, patients are increasingly interested in metal-free restoration. Glass-ceramics are particularly suitable for fabricating inlays, crowns and small bridges, as these materials achieve very strong, esthetic results. High-strength ceramics are preferred in situations where the material is exposed to high masticatory forces.

  4. Glycosaminoglycan derivatives: promising candidates for the design of functional biomaterials. (United States)

    Scharnweber, Dieter; Hübner, Linda; Rother, Sandra; Hempel, Ute; Anderegg, Ulf; Samsonov, Sergey A; Pisabarro, M Teresa; Hofbauer, Lorenz; Schnabelrauch, Matthias; Franz, Sandra; Simon, Jan; Hintze, Vera


    Numerous biological processes (tissue formation, remodelling and healing) are strongly influenced by the cellular microenvironment. Glycosaminoglycans (GAGs) are important components of the native extracellular matrix (ECM) able to interact with biological mediator proteins. They can be chemically functionalized and thereby modified in their interaction profiles. Thus, they are promising candidates for functional biomaterials to control healing processes in particular in health-compromised patients. Biophysical studies show that the interaction profiles between mediator proteins and GAGs are strongly influenced by (i) sulphation degree, (ii) sulphation pattern, and (iii) composition and structure of the carbohydrate backbone. Hyaluronan derivatives demonstrate a higher binding strength in their interaction with biological mediators than chondroitin sulphate for a comparable sulphation degree. Furthermore sulphated GAG derivatives alter the interaction profile of mediator proteins with their cell receptors or solute native interaction partners. These results are in line with biological effects on cells relevant for wound healing processes. This is valid for solute GAGs as well as those incorporated in collagen-based artificial ECM (aECMs). Prominent effects are (i) anti-inflammatory, immunomodulatory properties towards macrophages/dendritic cells, (ii) enhanced osteogenic differentiation of human mesenchymal stromal cells, (iii) altered differentiation of fibroblasts to myofibroblasts, (iv) reduced osteoclast activity and (v) improved osseointegration of dental implants in minipigs. The findings of our consortium Transregio 67 contribute to an improved understanding of structure-function relationships of GAG derivatives in their interaction with mediator proteins and cells. This will enable the design of bioinspired, functional biomaterials to selectively control and promote bone and skin regeneration.

  5. Current Strategies in Cardiovascular Biomaterial Functionalization

    Directory of Open Access Journals (Sweden)

    Karla Lehle


    Full Text Available Prevention of the coagulation cascade and platelet activation is the foremost demand for biomaterials in contact with blood. In this review we describe the underlying mechanisms of these processes and offer the current state of antithrombotic strategies. We give an overview of methods to prevent protein and platelet adhesion, as well as techniques to immobilize biochemically active molecules on biomaterial surfaces. Finally, recent strategies in biofunctionalization by endothelial cell seeding as well as their possible clinical applications are discussed.

  6. Medical applications for biomaterials in Bolivia

    CERN Document Server

    Arias, Susan


    This book investigates the potential medical benefits natural biomaterials can offer in developing countries by analyzing the case of Bolivia. The book explores the medical and health related applications of Bolivian commodities: quinoa, barley, sugarcane, corn, sorghum and sunflower seeds. This book helps readers better understand some of the key health concerns facing countries like Bolivia and how naturally derived biomaterials and therapeutics could help substantially alleviate many of their problems.

  7. Special Issue “Biomaterials and Bioprinting”

    Directory of Open Access Journals (Sweden)

    Chee Kai Chua


    Full Text Available The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm shift. This Special Issue focuses on biomaterials and bioprinting and contains eight articles covering a number of recent topics in this emerging area.

  8. Special Issue “Biomaterials and Bioprinting”



    The emergence of bioprinting in recent years represents a marvellous advancement in 3D printing technology. It expands the range of 3D printable materials from the world of non-living materials into the world of living materials. Biomaterials play an important role in this paradigm shift. This Special Issue focuses on biomaterials and bioprinting and contains eight articles covering a number of recent topics in this emerging area.

  9. Biomaterials innovation bundling technologies and life

    CERN Document Server

    Styhre, A


    Rapid advances in the life sciences means that there is now a far more detailed understanding of biological systems on the cellular, molecular and genetic levels. Sited at the intersection between the life sciences, the engineering sciences and the design sciences, innovations in the biomaterials industry are expected to garner increasing attention and play a key role in future development. This book examines the biomaterials innovations taking place in corporations and in academic research settings today.

  10. Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions (United States)

    Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele


    The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

  11. Biomaterials in tooth tissue engineering: a review. (United States)

    Sharma, Sarang; Srivastava, Dhirendra; Grover, Shibani; Sharma, Vivek


    Biomaterials play a crucial role in the field of tissue engineering. They are utilized for fabricating frameworks known as scaffolds, matrices or constructs which are interconnected porous structures that establish a cellular microenvironment required for optimal tissue regeneration. Several natural and synthetic biomaterials have been utilized for fabrication of tissue engineering scaffolds. Amongst different biomaterials, polymers are the most extensively experimented and employed materials. They can be tailored to provide good interconnected porosity, large surface area, adequate mechanical strengths, varying surface characterization and different geometries required for tissue regeneration. A single type of material may however not meet all the requirements. Selection of two or more biomaterials, optimization of their physical, chemical and mechanical properties and advanced fabrication techniques are required to obtain scaffold designs intended for their final application. Current focus is aimed at designing biomaterials such that they will replicate the local extra cellular environment of the native organ and enable cell-cell and cell-scaffold interactions at micro level required for functional tissue regeneration. This article provides an insight into the different biomaterials available and the emerging use of nano engineering principles for the construction of bioactive scaffolds in tooth regeneration.

  12. Adsorption behavior of heavy metals on biomaterials. (United States)

    Minamisawa, Mayumi; Minamisawa, Hiroaki; Yoshida, Shoichiro; Takai, Nobuharu


    We have investigated adsorption of Cd(II) and Pb(II) at pH 2-6.7 onto the biomaterials chitosan, coffee, green tea, tea, yuzu, aloe, and Japanese coarse tea, and onto the inorganic adsorbents, activated carbon and zeolite. High adsorptive capabilities were observed for all of the biomaterials at pH 4 and 6.7. In the adsorption of Cd(II), blend coffee, tea, green tea, and coarse tea have comparable loading capacities to activated carbon and zeolite. Although activated carbon, zeolite, and chitosan are utilized in a variety of fields such as wastewater treatment, chemical and metallurgical engineering, and analytical chemistry, these adsorbents are costly. On the other hand, processing of the test biomaterials was inexpensive, and all the biomaterials except for chitosan were able to adsorb large amounts of Pb(II) and Cd(II) ions after a convenient pretreatment of washing with water followed by drying. The high adsorption capability of the biomaterials prepared from plant materials is promising in the development of a novel, low-cost adsorbent. From these results, it is concluded that heavy metal removal using biomaterials would be an effective method for the economic treatment of wastewater. The proposed adsorption method was applied to the determination of amounts of Cd(II) and Pb(II) in water samples.

  13. Recombinant Exon-Encoded Resilins for Elastomeric Biomaterials (United States)

    Qin, Guokui; Rivkin, Amit; Lapidot, Shaul; Hu, Xiao; Arinus, Shira B.; Dgany, Or; Shoseyov, Oded; Kaplan, David L.


    Resilin is an elastomeric protein found in specialized regions of the cuticle of most insects, providing outstanding material properties including high resilience and fatigue lifetime for insect flight and jumping needs. Two exons (1 and 3) from the resilin gene in Drosophila melanogaster were cloned and the encoded proteins expressed as soluble products in Escherichia coli. A heat and salt precipitation method was used for efficient purification of the recombinant proteins. The proteins were solution cast from water and formed into rubber-like biomaterials via horseradish peroxidase-mediated cross-linking. Comparative studies of the two proteins expressed from the two different exons were investigated by Fourier Transform Infrared Spectroscopy (FTIR) and Circular Dichrosim (CD) for structural features. Little structural organization was found, suggesting structural order was not induced by the enzyme-mediateed dityrosine cross-links. Atomic Force Microscopy (AFM) was used to study the elastomeric properties of the uncross-linked and cross-linked proteins. The protein from exon 1 exhibited 90% resilience in comparison to 63% for the protein from exon 3, and therefore may be the more critical domain for functional materials to mimic native resilin. Further, the cross-linking of the recombinant exon 1 via the citrate-modified photo-Fenton reaction was explored as an alternative dityrosine mediated polymerization method and resulted in both highly elastic and adhesive materials. The citrate-modified photo-Fenton system may be suitable for in-vivo applications of resilin biomaterials. PMID:21963157

  14. Proteins at the Biomaterial Electrolyte Interface (United States)

    Tengvall, Pentti


    Proteins adsorb rapidly onto solid and polymeric surfaces because the association process is in the vast majority of cases energetically favourable, i.e. exothermic. The most common exceptions to this rule are hydrophilic interfaces with low net charge and high mobility, e.g. immobilized PEGs. Current research in the research area tries to understand and control unwanted and wanted adsorption by studying the adsorption kinetics, protein surface binding specificity, protein exchange at interfaces, and surface protein repulsion mechanisms. In blood plasma model systems humoral cascade reactions such as surface mediated coagulation and immune complement raise considerable interest due to the immediate association to blood compatibility, and in tissue applications the binding between surfaces and membrane receptors in cells and tissues. Thus, the understanding of interfacial events at the protein level is of large importance in applications such as blood and tissue contacting biomaterials, in vitro medical and biological diagnostics, food industry and in marine anti-fouling technology. Well described consequences of adsorption are a lowered system energy, increased system entropy, irreversible binding, conformational changes, specific surface/protein interactions, and in biomedical materials applications surface opsonization followed by cell-surface interactions and a host tissue response. This lecture will deal with some mechanisms known to be of importance for the adsorption processes, such as the influence of surface chemistry and surface energy, the composition of the protein solution, the Vroman effect, and residence time. Examples will be shown from ellipsometric experiments using different model surfaces in single/few protein solutions, and specific attention be given to blood serum and plasma experiments on coagulation and immune complement at interfaces.

  15. Novel High-Viscosity Polyacrylamidated Chitosan for Neural Tissue Engineering: Fabrication of Anisotropic Neurodurable Scaffold via Molecular Disposition of Persulfate-Mediated Polymer Slicing and Complexation

    Directory of Open Access Journals (Sweden)

    Viness Pillay


    Full Text Available Macroporous polyacrylamide-grafted-chitosan scaffolds for neural tissue engineering were fabricated with varied synthetic and viscosity profiles. A novel approach and mechanism was utilized for polyacrylamide grafting onto chitosan using potassium persulfate (KPS mediated degradation of both polymers under a thermally controlled environment. Commercially available high molecular mass polyacrylamide was used instead of the acrylamide monomer for graft copolymerization. This grafting strategy yielded an enhanced grafting efficiency (GE = 92%, grafting ratio (GR = 263%, intrinsic viscosity (IV = 5.231 dL/g and viscometric average molecular mass (MW = 1.63 × 106 Da compared with known acrylamide that has a GE = 83%, GR = 178%, IV = 3.901 dL/g and MW = 1.22 × 106 Da. Image processing analysis of SEM images of the newly grafted neurodurable scaffold was undertaken based on the polymer-pore threshold. Attenuated Total Reflectance-FTIR spectral analyses in conjugation with DSC were used for the characterization and comparison of the newly grafted copolymers. Static Lattice Atomistic Simulations were employed to investigate and elucidate the copolymeric assembly and reaction mechanism by exploring the spatial disposition of chitosan and polyacrylamide with respect to the reactional profile of potassium persulfate. Interestingly, potassium persulfate, a peroxide, was found to play a dual role initially degrading the polymers—“polymer slicing”—thereby initiating the formation of free radicals and subsequently leading to synthesis of the high molecular mass polyacrylamide-grafted-chitosan (PAAm-g-CHT—“polymer complexation”. Furthermore, the applicability of the uniquely grafted scaffold for neural tissue engineering was evaluated via PC12 neuronal cell seeding. The novel PAAm-g-CHT exhibited superior neurocompatibility in terms of cell infiltration owing to the anisotropic porous architecture, high molecular mass mediated robustness

  16. Biomaterials and medical devices a perspective from an emerging country

    CERN Document Server

    Hermawan, Hendra


    This book presents an introduction to biomaterials with the focus on the current development and future direction of biomaterials and medical devices research and development in Indonesia. It is the first biomaterials book written by selected academic and clinical experts experts on biomaterials and medical devices from various institutions and industries in Indonesia. It serves as a reference source for researchers starting new projects, for companies developing and marketing products and for governments setting new policies. Chapter one covers the fundamentals of biomaterials, types of biomaterials, their structures and properties and the relationship between them. Chapter two discusses unconventional processing of biomaterials including nano-hybrid organic-inorganic biomaterials. Chapter three addresses biocompatibility issues including in vitro cytotoxicity, genotoxicity, in vitro cell models, biocompatibility data and its related failure. Chapter four describes degradable biomaterial for medical implants...

  17. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin Volmer;


    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein...

  18. The role of phosphatidylinositol 3-kinase in neural cell adhesion molecule-mediated neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Ditlevsen, Dorte K; Køhler, Lene B; Pedersen, Martin V


    The neural cell adhesion molecule, NCAM, is known to stimulate neurite outgrowth from primary neurones and PC12 cells presumably through signalling pathways involving the fibroblast growth factor receptor (FGFR), protein kinase A (PKA), protein kinase C (PKC), the Ras-mitogen activated protein ki...

  19. Wear Characteristics of Metallic Biomaterials: A Review

    Directory of Open Access Journals (Sweden)

    Mohamed A. Hussein


    Full Text Available Metals are extensively used in a variety of applications in the medical field for internal support and biological tissue replacements, such as joint replacements, dental roots, orthopedic fixation, and stents. The metals and alloys that are primarily used in biomedical applications are stainless steels, Co alloys, and Ti alloys. The service period of a metallic biomaterial is determined by its abrasion and wear resistance. A reduction in the wear resistance of the implant results in the release of incompatible metal ions into the body that loosen the implant. In addition, several reactions may occur because of the deposition of wear debris in tissue. Therefore, developing biomaterials with high wear resistance is critical to ensuring a long life for the biomaterial. The aim of this work is to review the current state of knowledge of the wear of metallic biomaterials and how wear is affected by the material properties and conditions in terms of the type of alloys developed and fabrication processes. We also present a brief evaluation of various experimental test techniques and wear characterization techniques that are used to determine the tribological performance of metallic biomaterials.

  20. Heterogeneity of Scaffold Biomaterials in Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Lauren Edgar


    Full Text Available Tissue engineering (TE offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced. Ideally, biomaterials should closely mimic the characteristics of desired organ, their function and their in vivo environments. A review of biomaterials used in TE highlighted natural polymers, synthetic polymers, and decellularized organs as sources of scaffolding. Studies of discarded organs supported that decellularization offers a remedy to reducing waste of donor organs, but does not yet provide an effective solution to organ demand because it has shown varied success in vivo depending on organ complexity and physiological requirements. Review of polymer-based scaffolds revealed that a composite scaffold formed by copolymerization is more effective than single polymer scaffolds because it allows copolymers to offset disadvantages a single polymer may possess. Selection of biomaterials for use in TE is essential for transplant success. There is not, however, a singular biomaterial that is universally optimal.

  1. Microgel mechanics in biomaterial design. (United States)

    Saxena, Shalini; Hansen, Caroline E; Lyon, L Andrew


    The field of polymeric biomaterials has received much attention in recent years due to its potential for enhancing the biocompatibility of systems and devices applied to drug delivery and tissue engineering. Such applications continually push the definition of biocompatibility from relatively straightforward issues such as cytotoxicity to significantly more complex processes such as reducing foreign body responses or even promoting/recapitulating natural body functions. Hydrogels and their colloidal analogues, microgels, have been and continue to be heavily investigated as viable materials for biological applications because they offer numerous, facile avenues in tailoring chemical and physical properties to approach biologically harmonious integration. Mechanical properties in particular are recently coming into focus as an important manner in which biological responses can be altered. In this Account, we trace how mechanical properties of microgels have moved into the spotlight of research efforts with the realization of their potential impact in biologically integrative systems. We discuss early experiments in our lab and in others focused on synthetic modulation of particle structure at a rudimentary level for fundamental drug delivery studies. These experiments elucidated that microgel mechanics are a consequence of polymer network distribution, which can be controlled by chemical composition or particle architecture. The degree of deformability designed into the microgel allows for a defined response to an imposed external force. We have studied deformation in packed colloidal phases and in translocation events through confined pores; in all circumstances, microgels exhibit impressive deformability in response to their environmental constraints. Microgels further translate their mechanical properties when assembled in films to the properties of the bulk material. In particular, microgel films have been a large focus in our lab as building blocks for self

  2. Repair of injured spinal cord using biomaterial scaffolds and stem cells. (United States)

    Shrestha, Bikesh; Coykendall, Katherine; Li, Yongchao; Moon, Alex; Priyadarshani, Priyanka; Yao, Li


    The loss of neurons and degeneration of axons after spinal cord injury result in the loss of sensory and motor functions. A bridging biomaterial construct that allows the axons to grow through has been investigated for the repair of injured spinal cord. Due to the hostility of the microenvironment in the lesion, multiple conditions need to be fulfilled to achieve improved functional recovery. A scaffold has been applied to bridge the gap of the lesion as contact guidance for axonal growth and to act as a vehicle to deliver stem cells in order to modify the microenvironment. Stem cells may improve functional recovery of the injured spinal cord by providing trophic support or directly replacing neurons and their support cells. Neural stem cells and mesenchymal stem cells have been seeded into biomaterial scaffolds and investigated for spinal cord regeneration. Both natural and synthetic biomaterials have increased stem cell survival in vivo by providing the cells with a controlled microenvironment in which cell growth and differentiation are facilitated. This optimal multi‒disciplinary approach of combining biomaterials, stem cells, and biomolecules offers a promising treatment for the injured spinal cord.

  3. Synthetic biomaterials for pelvic floor reconstruction. (United States)

    Karlovsky, Matthew E; Kushner, Leslie; Badlani, Gopal H


    Pelvic organ prolapse and stress urinary incontinence increase with age. The increasing proportion of the aging female population is likely to result in a demand for care of pelvic floor prolapse and incontinence. Experimental evidence of altered connective tissue metabolism may predispose to pelvic floor dysfunction, supporting the use of biomaterials, such as synthetic mesh, to correct pelvic fascial defects. Re-establishing pelvic support and continence calls for a biomaterial to be inert, flexible, and durable and to simultaneously minimize infection and erosion risk. Mesh as a biomaterial has evolved considerably throughout the past half century to the current line that combines ease of use, achieves good outcomes, and minimizes risk. This article explores the biochemical basis for pelvic floor attenuation and reviews various pelvic reconstructive mesh materials, their successes, failures, complications, and management.

  4. Smart self-assembled hybrid hydrogel biomaterials. (United States)

    Kopeček, Jindřich; Yang, Jiyuan


    Hybrid biomaterials are systems created from components of at least two distinct classes of molecules, for example, synthetic macromolecules and proteins or peptide domains. The synergistic combination of two types of structures may produce new materials that possess unprecedented levels of structural organization and novel properties. This Review focuses on biorecognition-driven self-assembly of hybrid macromolecules into functional hydrogel biomaterials. First, basic rules that govern the secondary structure of peptides are discussed, and then approaches to the specific design of hybrid systems with tailor-made properties are evaluated, followed by a discussion on the similarity of design principles of biomaterials and macromolecular therapeutics. Finally, the future of the field is briefly outlined.

  5. Imaging challenges in biomaterials and tissue engineering. (United States)

    Appel, Alyssa A; Anastasio, Mark A; Larson, Jeffery C; Brey, Eric M


    Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research. Traditionally, histological and immunohistochemical techniques have been used to evaluate engineered tissues. However, these methods do not allow for an accurate volume assessment, are invasive, and do not provide information on functional status. Imaging techniques are needed that enable non-destructive, longitudinal, quantitative, and three-dimensional analysis of TERM strategies. This review focuses on evaluating the application of available imaging modalities for assessment of biomaterials and tissue in TERM applications. Included is a discussion of limitations of these techniques and identification of areas for further development.

  6. Complement inhibition in biomaterial- and biosurface-induced thromboinflammation. (United States)

    Ekdahl, Kristina N; Huang, Shan; Nilsson, Bo; Teramura, Yuji


    Therapeutic medicine today includes a vast number of procedures involving the use of biomaterials, transplantation of therapeutic cells or cell clusters, as well as of solid organs. These treatment modalities are obviously of great benefit to the patient, but also present a great challenge to the innate immune system, since they involve direct exposure of non-biological materials, cells of non-hematological origin as well as endothelial cells, damaged by ischemia-perfusion in solid organs to proteins and cells in the blood. The result of such an exposure may be an inappropriate activation of the complement and contact/kallikrein systems, which produce mediators capable of triggering the platelets and PMNs and monocytes, which can ultimately result in thrombotic and inflammatory (i.e., a thrombo-inflammatory) response to the treatment modality. In this concept review, we give an overview of the mechanisms of recognition within the innate immunity system, with the aim to identify suitable points for intervention. Finally, we discuss emerging and promising techniques for surface modification of biomaterials and cells with specific inhibitors in order to diminish thromboinflammation and improve clinical outcome.

  7. Regulatory affairs for biomaterials and medical devices

    CERN Document Server

    Amato, Stephen F; Amato, B


    All biomaterials and medical devices are subject to a long list of regulatory practises and policies which must be adhered to in order to receive clearance. This book provides readers with information on the systems in place in the USA and the rest of the world. Chapters focus on a series of procedures and policies including topics such as commercialization, clinical development, general good practise manufacturing and post market surveillance.Addresses global regulations and regulatory issues surrounding biomaterials and medical devicesEspecially useful for smaller co

  8. Alkylation of Chitosan as Nerve Conduit Biomaterial

    Institute of Scientific and Technical Information of China (English)

    邓劲光; 公衍道; 程明愚; 赵南明; 张秀芳


    Chitosan under physiological conditions is a degradable and biocompatible biomaterial with a wide variety of useful physicochemical properties. However, as a nerve conduit biomaterial, its solubility was very low, so chitosan was modified chemically to enhance its solubility. The free amino groups of long molecular chains in chitosan are responsible for its solubility, and the solubility could be adjusted by controlling the free amidogen capacity with N-alkylation. The results show that the solubility of N-alkylation chitosan is increased to 10%, which is an increase of 500%.

  9. Facile design of biomaterials by 'click' chemistry

    DEFF Research Database (Denmark)

    Hvilsted, Søren


    The advent of the so‐called ‘click chemistry’ a decade ago has significantly improved the chemical toolbox for producing novel biomaterials. This review focuses primarily on the application of Cu(I)‐catalysed azide–alkyne 1,3‐cycloadditon in the preparation of numerous, diverse biomaterials...... chemistry is elaborated. The present state of creating functional and biologically active surfaces by click chemistry is presented. Finally, conducting surfaces based on an azide‐functionalized polymer with prospective biological sensor potential are introduced. Copyright © 2012 Society of Chemical Industry...

  10. Sustainable Biomaterials: Current Trends, Challenges and Applications

    Directory of Open Access Journals (Sweden)

    Girish Kumar Gupta


    Full Text Available Biomaterials and sustainable resources are two complementary terms supporting the development of new sustainable emerging processes. In this context, many interdisciplinary approaches including biomass waste valorization and proper usage of green technologies, etc., were brought forward to tackle future challenges pertaining to declining fossil resources, energy conservation, and related environmental issues. The implementation of these approaches impels its potential effect on the economy of particular countries and also reduces unnecessary overburden on the environment. This contribution aims to provide an overview of some of the most recent trends, challenges, and applications in the field of biomaterials derived from sustainable resources.

  11. Sustainable Biomaterials: Current Trends, Challenges and Applications. (United States)

    Kumar Gupta, Girish; De, Sudipta; Franco, Ana; Balu, Alina Mariana; Luque, Rafael


    Biomaterials and sustainable resources are two complementary terms supporting the development of new sustainable emerging processes. In this context, many interdisciplinary approaches including biomass waste valorization and proper usage of green technologies, etc., were brought forward to tackle future challenges pertaining to declining fossil resources, energy conservation, and related environmental issues. The implementation of these approaches impels its potential effect on the economy of particular countries and also reduces unnecessary overburden on the environment. This contribution aims to provide an overview of some of the most recent trends, challenges, and applications in the field of biomaterials derived from sustainable resources.

  12. The mechanism of neurally mediated syncope assessed by an ambulatory radionuclide monitoring system and heart rate variability indices during head-up tilt

    Energy Technology Data Exchange (ETDEWEB)

    Hosaka, Haruhiko [Self Defense Force Central Hospital, Tokyo (Japan); Takase, Bonpei; Ohsuzu, Fumitaka [National Defense Medical Coll., Tokorozawa, Saitama (Japan); Kurita, Akira [National Defense Medical Coll., Tokorozawa, Saitama (Japan). Research Center


    Previously, we tested the hypothesis that the great decline in left ventricular volume during head-up tilt test could trigger ventricular mechanoreceptor activation, using ambulatory radionuclide monitoring system (C-VEST system). The aim of this study is to investigate the mechanism of tilt-induced syncope further, based on our previous report. We measured the temporal changes in left ventricular volume, ejection fraction, cardiac output, and heart rate variability indices during head-up tilt test in 34 patients with syncope of an undetermined etiology. Twenty-two patients and a positive response (P group). Twelve patients showed a negative response (N group). Before syncope, left ventricular volume declined (P group, diastolic volume; -7.9{+-}6.8%: systolic volume; -23.3{+-}33.8%: N group, diastolic volume; -2.5{+-}1.9%: systolic volume; 0.6{+-}9.5%: p<0.05), ejection fraction increased (P group, 3.9{+-}2.5%; N group, -3.5{+-}7.2%; p<0.005), and high frequency spectra increased (P group, 12.0{+-}20.3%; N group, 3.1{+-}9.7%; p<0.05), more extremely in the P group than in the N group. The value of the high frequency spectra before the head-up tilt test was significantly higher in the P group than in the N group (P group, 5.8{+-}0.9 ms; N group, 5.0{+-}1.1 ms; p<0.05). The precise evaluation of left ventricular volume by ambulatory radionuclide monitoring system combined with a heart rate variability analysis is considered to be useful for clarifying the pathophysiology of neurally mediated syncope. Patients with neurally mediated syncope have higher baseline parasympathetic tone than normal population. (author)

  13. Biomaterials supported CdS nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Balu, Alina M. [Institute of Physical Chemistry ' Ilie Murgulescu' , Spl. Independentei 202, 060021 Bucharest (Romania); Departamento de Quimica Organica, Campus de Rabanales, Edificio Marie Curie, Ctra Nnal IV, Km 396, Universidad de Cordoba, E-14014 Cordoba (Spain); Campelo, Juan M. [Departamento de Quimica Organica, Campus de Rabanales, Edificio Marie Curie, Ctra Nnal IV, Km 396, Universidad de Cordoba, E-14014 Cordoba (Spain); Luque, Rafael, E-mail: [Departamento de Quimica Organica, Campus de Rabanales, Edificio Marie Curie, Ctra Nnal IV, Km 396, Universidad de Cordoba, E-14014 Cordoba (Spain); Rajabi, Fatemeh [Department of Science, Payame Noor University, PO Box 878, Qazvin (Iran, Islamic Republic of); Romero, Antonio A. [Departamento de Quimica Organica, Campus de Rabanales, Edificio Marie Curie, Ctra Nnal IV, Km 396, Universidad de Cordoba, E-14014 Cordoba (Spain)


    CdS quantum dot materials were prepared through a simple room temperature deposition of CdS nanocrystals on biomaterials including starch and chitosan. Materials obtained were found to contain differently distributed CdS nanocrystals on the surface of the biopolymers, making them potentially interesting for biomedical applications as contrast agents and/or in photocatalysis.

  14. Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Lianhua Bai; Jordan Hecker; Amber Kerstetter; Robert H.Miller


    Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis (MS),therefore it is important to identify the most effective cell types that promote myelin repair.Several components contribute to the relative benefits of specific cell types including the overall efficacy of the cell therapy,the reproducibility of treatment,the mechanisms of action of distinct cell types and the ease of isolation and generation of therapeutic populations.A range of distinct cell populations promote functional recovery in animal models of MS including neural stem cells and mesenchymal stem cells derived from different tissues.Each of these cell populations has advantages and disadvantages and likely works through distinct mechanisms.The relevance of such mechanisms to myelin repair in the adult central nervous system is unclear since the therapeutic cells are generally derived from developing animals.Here we describe the isolation and characterization of a population of neural cells from the adult spinal cord that are characterized by the expression of the cell surface glycoprotein NG2.In functional studies,injection of adult NG2+ cells into mice with ongoing MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) enhanced remyelination in the CNS while the number of CD3+ T cells in areas of spinal cord demyelination was reduced approximately three-fold.In vivo studies indicated that in EAE,NG2+ cells stimulated endogenous repair while in vitro they responded to signals in areas of induced inflammation by differentiating into oligodendrocytes.These results suggested that adult NG2+ cells represent a useful cell population for promoting neural repair in a variety of different conditions including demyelinating diseases such as MS.

  15. Silk film biomaterials for ocular surface repair (United States)

    Lawrence, Brian David

    Current biomaterial approaches for repairing the cornea's ocular surface upon injury are partially effective due to inherent material limitations. As a result there is a need to expand the biomaterial options available for use in the eye, which in turn will help to expand new clinical innovations and technology development. The studies illustrated here are a collection of work to further characterize silk film biomaterials for use on the ocular surface. Silk films were produced from regenerated fibroin protein solution derived from the Bombyx mori silkworm cocoon. Methods of silk film processing and production were developed to produce consistent biomaterials for in vitro and in vivo evaluation. A wide range of experiments was undertaken that spanned from in vitro silk film material characterization to in vivo evaluation. It was found that a variety of silk film properties could be controlled through a water-annealing process. Silk films were then generated that could be use in vitro to produce stratified corneal epithelial cell sheets comparable to tissue grown on the clinical standard substrate of amniotic membrane. This understanding was translated to produce a silk film design that enhanced corneal healing in vivo on a rabbit injury model. Further work produced silk films with varying surface topographies that were used as a simplified analog to the corneal basement membrane surface in vitro. These studies demonstrated that silk film surface topography is capable of directing corneal epithelial cell attachment, growth, and migration response. Most notably epithelial tissue development was controllably directed by the presence of the silk surface topography through increasing cell sheet migration efficiency at the individual cellular level. Taken together, the presented findings represent a comprehensive characterization of silk film biomaterials for use in ocular surface reconstruction, and indicate their utility as a potential material choice in the

  16. A novel function of DELTA-NOTCH signalling mediates the transition from proliferation to neurogenesis in neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Barbara Hämmerle

    Full Text Available A complete account of the whole developmental process of neurogenesis involves understanding a number of complex underlying molecular processes. Among them, those that govern the crucial transition from proliferative (self-replicating to neurogenic neural progenitor (NP cells remain largely unknown. Due to its sequential rostro-caudal gradients of proliferation and neurogenesis, the prospective spinal cord of the chick embryo is a good experimental system to study this issue. We report that the NOTCH ligand DELTA-1 is expressed in scattered cycling NP cells in the prospective chick spinal cord preceding the onset of neurogenesis. These Delta-1-expressing progenitors are placed in between the proliferating caudal neural plate (stem zone and the rostral neurogenic zone (NZ where neurons are born. Thus, these Delta-1-expressing progenitors define a proliferation to neurogenesis transition zone (PNTZ. Gain and loss of function experiments carried by electroporation demonstrate that the expression of Delta-1 in individual progenitors of the PNTZ is necessary and sufficient to induce neuronal generation. The activation of NOTCH signalling by DELTA-1 in the adjacent progenitors inhibits neurogenesis and is required to maintain proliferation. However, rather than inducing cell cycle exit and neuronal differentiation by a typical lateral inhibition mechanism as in the NZ, DELTA-1/NOTCH signalling functions in a distinct manner in the PNTZ. Thus, the inhibition of NOTCH signalling arrests proliferation but it is not sufficient to elicit neuronal differentiation. Moreover, after the expression of Delta-1 PNTZ NP continue cycling and induce the expression of Tis21, a gene that is upregulated in neurogenic progenitors, before generating neurons. Together, these experiments unravel a novel function of DELTA-NOTCH signalling that regulates the transition from proliferation to neurogenesis in NP cells. We hypothesize that this novel function is evolutionary

  17. Brief Overview on Nitinol as Biomaterial

    Directory of Open Access Journals (Sweden)

    Abdul Wadood


    Full Text Available Shape memory alloys remember their shape due to thermoelastic martensitic phase transformation. These alloys have advantages in terms of large recoverable strain and these alloys can exert continuous force during use. Equiatomic NiTi, also known as nitinol, has a great potential for use as a biomaterial as compared to other conventional materials due to its shape memory and superelastic properties. In this paper, an overview of recent research and development related to NiTi based shape memory alloys is presented. Applications and uses of NiTi based shape memory alloys as biomaterials are discussed. Biocompatibility issues of nitinol and researchers’ approach to overcome this problem are also briefly discussed.

  18. Neural mechanisms mediating the effects of expectation in visceral placebo analgesia: an fMRI study in healthy placebo responders and nonresponders. (United States)

    Elsenbruch, Sigrid; Kotsis, Vassilios; Benson, Sven; Rosenberger, Christina; Reidick, Daniel; Schedlowski, Manfred; Bingel, Ulrike; Theysohn, Nina; Forsting, Michael; Gizewski, Elke R


    This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N=36 healthy subjects, the blood oxygen level-dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0%>100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain.

  19. The role of the hippocampus in mediating emotional responses to nicotine and cannabinoids: a possible neural substrate for functional interactions. (United States)

    Viveros, María-Paz; Marco, Eva-María; Llorente, Ricardo; Lamota, Laura


    The endocannabinoid system is involved in the regulation of behavioural and physiological stress-related responses. Nicotine exerts complex effects on emotional behaviour, and its withdrawal may result in depressive and anxiogenic-like symptoms. Cannabinoid receptor agonists and nicotine induce biphasic effects in diverse tests of unconditioned anxiety, alter adrenocortical activity and affect hippocampus-dependent contextual fear conditioning. Upon exposure to stressful stimuli, central endocannabinoid and cholinergic systems appear to be activated in key limbic areas such as hippocampus and amygdala, which might contribute to adaptive cognitive and emotional strategies to cope with aversive situations. Numerous studies indicate the existence of functional interactions between nicotine and cannabinoids, particularly in relation to anxiety-related processes. An overlapping distribution of CB1 and nicotinic acetylcholine receptors in the hippocampus is observed and the endocannabinoid system exerts a modulatory role over the hippocampal cholinergic system. In this review, we point to the hippocampus as a relevant neural substrate for cannabinoid-nicotine interactions, notably as regards emotional responses. After a general description of the cannabinoid and nicotinic systems, we review their implications in unconditioned anxiety, depressive-like behaviour and fear conditioning. Then we discuss the role of both systems in modulating stress-induced changes at cellular, endocrine and behavioural levels and their possible involvement in hippocampal neurogenesis. Although we mainly focus on animal data, some relevant human studies are also discussed.

  20. Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

    Directory of Open Access Journals (Sweden)

    Hideo eOtsuna


    Full Text Available Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

  1. Calponin 2 Acts As an Effector of Noncanonical Wnt-Mediated Cell Polarization during Neural Crest Cell Migration

    Directory of Open Access Journals (Sweden)

    Bärbel Ulmer


    Full Text Available Neural crest cells (NCCs migrate throughout the embryo to differentiate into cell types of all germ layers. Initial directed NCC emigration relies on planar cell polarity (PCP, which through the activity of the small GTPases RhoA and Rac governs the actin-driven formation of polarized cell protrusions. We found that the actin binding protein calponin 2 (Cnn2 was expressed in protrusions at the leading edge of migratory NCCs in chicks and frogs. Cnn2 knockdown resulted in NCC migration defects in frogs and chicks and randomized outgrowth of cell protrusions in NCC explants. Morphant cells showed central stress fibers at the expense of the peripheral actin network. Cnn2 acted downstream of Wnt/PCP, as migration defects induced by dominant-negative Wnt11 or inhibition of RhoA function were rescued by Cnn2 knockdown. These results suggest that Cnn2 modulates actin dynamics during NCC migration as an effector of noncanonical Wnt/PCP signaling.

  2. Murine neural stem cells model Hunter disease in vitro: glial cell-mediated neurodegeneration as a possible mechanism involved. (United States)

    Fusar Poli, E; Zalfa, C; D'Avanzo, F; Tomanin, R; Carlessi, L; Bossi, M; Nodari, L Rota; Binda, E; Marmiroli, P; Scarpa, M; Delia, D; Vescovi, A L; De Filippis, L


    Mucopolysaccharidosis type II (MPSII or Hunter Syndrome) is a lysosomal storage disorder caused by the deficit of iduronate 2-sulfatase (IDS) activity and characterized by progressive systemic and neurological impairment. As the early mechanisms leading to neuronal degeneration remain elusive, we chose to examine the properties of neural stem cells (NSCs) isolated from an animal model of the disease in order to evaluate whether their neurogenic potential could be used to recapitulate the early phases of neurogenesis in the brain of Hunter disease patients. Experiments here reported show that NSCs derived from the subventricular zone (SVZ) of early symptomatic IDS-knockout (IDS-ko) mouse retained self-renewal capacity in vitro, but differentiated earlier than wild-type (wt) cells, displaying an evident lysosomal aggregation in oligodendroglial and astroglial cells. Consistently, the SVZ of IDS-ko mice appeared similar to the wt SVZ, whereas the cortex and striatum presented a disorganized neuronal pattern together with a significant increase of glial apoptotic cells, suggesting that glial degeneration likely precedes neuronal demise. Interestingly, a very similar pattern was observed in the brain cortex of a Hunter patient. These observations both in vitro, in our model, and in vivo suggest that IDS deficit seems to affect the late phases of neurogenesis and/or the survival of mature cells rather than NSC self-renewal. In particular, platelet-derived growth factor receptor-α-positive (PDGFR-α+) glial progenitors appeared reduced in both the IDS-ko NSCs and in the IDS-ko mouse and human Hunter brains, compared with the respective healthy controls. Treatment of mutant NSCs with IDS or PDGF throughout differentiation was able to increase the number of PDGFR-α+ cells and to reduce that of apoptotic cells to levels comparable to wt. This evidence supports IDS-ko NSCs as a reliable in vitro model of the disease, and suggests the rescue of PDGFR-α+ glial cells as a

  3. GABAA receptor-mediated feedforward and feedback inhibition differentially modulate the gain and the neural code transformation in hippocampal CA1 pyramidal cells. (United States)

    Jang, Hyun Jae; Park, Kyerl; Lee, Jaedong; Kim, Hyuncheol; Han, Kyu Hun; Kwag, Jeehyun


    Diverse variety of hippocampal interneurons exists in the CA1 area, which provides either feedforward (FF) or feedback (FB) inhibition to CA1 pyramidal cell (PC). However, how the two different inhibitory network architectures modulate the computational mode of CA1 PC is unknown. By investigating the CA3 PC rate-driven input-output function of CA1 PC using in vitro electrophysiology, in vitro-simulation of inhibitory network, and in silico computational modeling, we demonstrated for the first time that GABAA receptor-mediated FF and FB inhibition differentially modulate the gain, the spike precision, the neural code transformation and the information capacity of CA1 PC. Recruitment of FF inhibition buffered the CA1 PC spikes to theta-frequency regardless of the input frequency, abolishing the gain and making CA1 PC insensitive to its inputs. Instead, temporal variability of the CA1 PC spikes was increased, promoting the rate-to-temporal code transformation to enhance the information capacity of CA1 PC. In contrast, the recruitment of FB inhibition sub-linearly transformed the input rate to spike output rate with high gain and low spike temporal variability, promoting the rate-to-rate code transformation. These results suggest that GABAA receptor-mediated FF and FB inhibitory circuits could serve as network mechanisms for differentially modulating the gain of CA1 PC, allowing CA1 PC to switch between different computational modes using rate and temporal codes ad hoc. Such switch will allow CA1 PC to efficiently respond to spatio-temporally dynamic inputs and expand its computational capacity during different behavioral and neuromodulatory states in vivo.

  4. Current concepts of regenerative biomaterials in implant dentistry

    Directory of Open Access Journals (Sweden)

    Annapurna Ahuja


    Full Text Available The primary objective of any implant system is to achieve firm fixation to the bone and this could be influenced by biomechanical as well as biomaterial selection. An array of materials is used in the replacement of missing teeth through implantation. The appropriate selection of biomaterials directly influences the clinical success and longevity of implants. Thus the clinician needs to have adequate knowledge of the various biomaterials and their properties for their judicious selection and application in his/her clinical practice. The recent materials such as bioceramics and composite biomaterials that are under consideration and investigation have a promising future. For optimal performance, implant biomaterials should have suitable mechanical strength, biocompatibility, and structural biostability in the physiological environment. This article reviews the various implant biomaterials and their ease of use in implant dentistry.

  5. Protective Effect of Electroacupuncture on Neural Myelin Sheaths is Mediated via Promotion of Oligodendrocyte Proliferation and Inhibition of Oligodendrocyte Death After Compressed Spinal Cord Injury. (United States)

    Huang, Siqin; Tang, Chenglin; Sun, Shanquan; Cao, Wenfu; Qi, Wei; Xu, Jin; Huang, Juan; Lu, Weitian; Liu, Qian; Gong, Biao; Zhang, Yi; Jiang, Jin


    Electroacupuncture (EA) has been used worldwide to treat demyelinating diseases, but its therapeutic mechanism is poorly understood. In this study, a custom-designed model of compressed spinal cord injury (CSCI) was used to induce demyelination. Zusanli (ST36) and Taixi (KI3) acupoints of adult rats were stimulated by EA to demonstrate its protective effect. At 14 days after EA, both locomotor skills and ultrastructural features of myelin sheath were significantly improved. Phenotypes of proliferating cells were identified by double immunolabeling of 5-ethynyl-2'-deoxyuridine with antibodies to cell markers: NG2 [oligodendrocyte precursor cell (OPC) marker], 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) (oligodendrocyte marker), and glial fibrillary acidic protein (GFAP) (astrocyte marker). EA enhanced the proliferation of OPCs and CNPase, as well as the differentiation of OPCs by promoting Olig2 (the basic helix-loop-helix protein) and attenuating Id2 (the inhibitor of DNA binding 2). EA could also improve myelin basic protein (MBP) and protect existing oligodendrocytes from apoptosis by inhibiting caspase-12 (a representative of endoplasmic reticulum stress) and cytochrome c (an apoptotic factor and hallmark of mitochondria). Therefore, our results indicate that the protective effect of EA on neural myelin sheaths is mediated via promotion of oligodendrocyte proliferation and inhibition of oligodendrocyte death after CSCI.

  6. Impaired functions of neural stem cells by abnormal nitric oxide-mediated signaling in an in vitro model of Niemann-Pick type C disease

    Institute of Scientific and Technical Information of China (English)

    Sun-Jung Kim; Myung-Sin Lim; Soo-Kyung Kang; Yong-Soon Lee; Kyung-Sun Kang


    Nitric oxide (NO) has been implicated in the promotion of neurodegeneration.However,little is known about the relationship between NO and the self-renewal or differentiation capacity of neural stem cells (NSCs) in neurodegenerative disease.In this study,we investigated the effect of NO on self-renewal of NSCs in an animal model for Niemann-Pick type C (NPC) disease.We found that NO production was significantly increased in NSCs from NPC1-deficient mice (NPC1-/-),which showed reduced NSC self-renewal.The number of nestin-positive cells and the size of neurospheres were both significantly decreased.The expression of NO synthase (NOS) was increased in neurospheres derived from the brain of NPC1-/- mice in comparison to wild-type neurospheres.NO-mediated activation of glycogen synthase kinase-3β(GSK3β) and caspase-3 was also observed in NSCs from NPC1-/- mice.The self-renewal ability of NSCs from NPC1-/- mice was restored by an NOS inhibitor,L-NAME,which resulted in the inhibition of GSK3β and caspase-3.In addition,the differentiation ability of NSCs was partially restored and the number of Fluoro-Jade C-positive degenerating neurons was reduced.These data suggest that overproduction of NO in NPC disease impaired the self-renewal of NSCs.Control of NO production may be key for the treatment of NPC disease.

  7. Relationship between human evolution and neurally mediated syncope disclosed by the polymorphic sites of the adrenergic receptor gene α2B-AR.

    Directory of Open Access Journals (Sweden)

    Tomoyoshi Komiyama

    Full Text Available The objective of this study was to clarify the effects of disease on neurally mediated syncope (NMS during an acute stress reaction. We analyzed the mechanism of the molecular interaction and the polymorphisms of the alpha-2 adrenoreceptor (α2B-AR gene as the potential psychiatric cause of incentive stress. We focused on the following three genotypes of the repeat polymorphism site at Glu 301-303 in the α2B-AR gene: Glu12/12, Glu12/9, and Glu9/9. On the basis of our clinical research, NMS is likely to occur in people with the Glu12/9 heterotype. To verify this, we assessed this relationship with the interaction of Gi protein and adenylate cyclase by in silico analysis of the Glu12/9 heterotype. By measuring the difference in the dissociation time of the Gi-α subunit twice, we found that the Glu12/9 heterotype suppressed the action of adenylate cyclase longer than the Glu homotypes. As this difference in the Glu repeat number effect is thought to be one of the causes of NMS, we investigated the evolutionary significance of the Glu repeat number. Glu8 was originally repeated in simians, while the Glu12 repeats occurred over time during the evolution of bipedalism in humans. Taken with the Glu12 numbers, NMS would likely become a defensive measure to prevent significant blood flow to the human brain.

  8. Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro

    Directory of Open Access Journals (Sweden)

    Wei Cheng


    Full Text Available Background/Aims: There is interest in drugs and rehabilitation methods to enhance neurogenesis and improve neurological function after brain injury or degeneration. Resveratrol may enhance hippocampal neurogenesis and improve hippocampal atrophy in chronic fatigue mice and prenatally stressed rats. However, its effect and mechanism of neurogenesis after stroke is less well understood. Sonic hedgehog (Shh signaling is crucial for neurogenesis in the embryonic and adult brain, but relatively little is known about the role of Shh signaling in resveratrol-enhanced neurogenesis after stroke. Methods: Neural stem cells (NSCs before oxygen-glucose deprivation/reoxygenation (OGD/R in vitro were pretreated with resveratrol with or without cyclopamine. Survival and proliferation of NSCs was assessed by the CCK8 assay and BrdU immunocytochemical staining. The expressions and activity of signaling proteins and mRNAs were detected by immunocytochemistry, Western blotting, and RT-PCR analysis. Results: Resveratrol significantly increased NSCs survival and proliferation in a concentration-dependent manner after OGD/R injury in vitro. At the same time, the expression of Patched-1, Smoothened (Smo, and Gli-1 proteins and mRNAs was upregulated, and Gli-1 entered the nucleus, which was inhibited by cyclopamine, a Smo inhibitor. Conclusion: Shh signaling mediates resveratrol to increase NSCs proliferation after OGD/R injury in vitro.

  9. Biomaterials approaches to modeling macrophage-extracellular matrix interactions in the tumor microenvironment. (United States)

    Springer, Nora L; Fischbach, Claudia


    Tumors are characterized by aberrant extracellular matrix (ECM) remodeling and chronic inflammation. While advances in biomaterials and tissue engineering strategies have led to important new insights regarding the role of ECM composition, structure, and mechanical properties in cancer in general, the functional link between these parameters and macrophage phenotype is poorly understood. Nevertheless, increasing experimental evidence suggests that macrophage behavior is similarly controlled by physicochemical properties of the ECM and consequential changes in mechanosignaling. Here, we will summarize the current knowledge of macrophage biology and ECM-mediated differences in mechanotransduction and discuss future opportunities of biomaterials and tissue engineering platforms to interrogate the functional relationship between these parameters and their relevance to cancer.

  10. Exploiting serum interactions with cationic biomaterials enables label-free circulating tumor cell isolation (United States)

    Castellanos, Carlos

    Herein we investigate the role charged biomaterials and fluid dielectric properties have on microfluidic capture and isolation of circulating tumor cells. We determine that heparan sulfate proteoglycans on cancer cell surfaces are responsible for elevated electric charge of cancer cells compared with white blood cells and that these proteoglycans help mediate adhesive interactions between cells and charged surfaces in albumin-containing fluids. Cancer cell firm adhesion to charged surfaces persists when cells are bathed in up to 1% (w/v) human albumin solution, while white blood cell adhesion is nearly abrogated. As many protocols rely on electrical interactions between cells and biomaterials, our study could reveal a new determinant of efficient adhesion and targeting of specific tissue types in the context of a biological fluid environment.

  11. Static stretch affects neural stem cell differentiation in an extracellular matrix-dependent manner (United States)

    Arulmoli, Janahan; Pathak, Medha M.; McDonnell, Lisa P.; Nourse, Jamison L.; Tombola, Francesco; Earthman, James C.; Flanagan, Lisa A.


    Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial stretch to NSPCs and examined effects on differentiation. We found static stretch specifically impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Generation of oligodendrocytes from NSPCs was reduced on laminin, an outcome likely mediated by the α6 laminin-binding integrin, whereas similar effects were not observed for NSPCs on fibronectin. Our data demonstrate a direct role for tensile strain in dictating the lineage choice of NSPCs and indicate the dependence of this phenomenon on specific substrate materials, which should be taken into account for the design of biomaterials for NSPC transplantation.

  12. Biomaterial microenvironments to support the generation of new neurons in the adult brain. (United States)

    Conway, Anthony; Schaffer, David V


    Neural stem cells (NSC) in two regions of the adult mammalian brain--the subventricular zone (SVZ) and hippocampus--continuously generate new neurons, enabled by a complex repertoire of factors that precisely regulate the activation, proliferation, differentiation, and integration of the newborn cells. A growing number of studies also report low-level neurogenesis in regions of the adult brain outside these established neurogenic niches--potentially via NSC recruitment or activation of local, quiescent NSCs--under perturbations such as ischemia, cell death, or viral gene delivery of proneural growth factors. We have explored whether implantation of engineered biomaterials can stimulate neurogenesis in normally quiescent regions of the brain. Specifically, recombinant versions of factors found within the NSC microenvironment, Sonic hedgehog, and ephrin-B2 were conjugated to long polymers, thereby creating highly bioactive, multivalent ligands that begin to emulate components of the neurogenic niche. In this engineered biomaterial microenvironment, new neuron formation was observed in normally non-neurogenic regions of the brain, the striatum, and the cortex, and combining these multivalent biomaterials with stromal cell-derived factor-1α increased neuronal commitment of newly divided cells seven- to eightfold in these regions. Additionally, the decreased hippocampal neurogenesis of geriatric rodents was partially rescued toward levels of young animals. We thus demonstrate for the first time de novo neurogenesis in both the cortex and striatum of adult rodents stimulated solely by delivery of synthetic biomaterial forms of proteins naturally found within adult neurogenic niches, offering the potential to replace neurons lost in neurodegenerative disease or injury as an alternative to cell implantation.

  13. Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages. (United States)

    Shikata, Yayoi; Okada, Toshiaki; Hashimoto, Mitsuhiro; Ellis, Tammy; Matsumaru, Daisuke; Shiroishi, Toshihiko; Ogawa, Masaharu; Wainwright, Brandon; Motoyama, Jun


    Sonic hedgehog (Shh) signaling regulates cell differentiation and proliferation during brain development. However, the role of Shh in neurogenesis during late gestation (embryonic day 13.5-18.5) remains unclear. Herein, we used a genetic approach and in utero electroporation to investigate the role of mouse Shh and patched homolog 1 (Ptch1), the putative receptor for Shh. Proliferating cortical intermediate (basal) progenitor cells (IPCs) were severely reduced in Shh mutant mice, suggesting that endogenous Shh signaling could play an essential role in cortical IPC development. During cortical neurogenesis, strong upregulation of Shh signaling enhanced the transition from ventricular zone (VZ) progenitors to ventralized IPCs, while low levels of signaling enhanced the generation and proliferation of cortical IPCs in the subventricular zone. The effects of Shh upregulation in this study were consistent with a phenotype of conditional loss of function of Ptch1, and the phenotype of a hypomorphic allele of Ptch1, respectively. These data indicated that endogenous Ptch1 mediates the broad effects of Shh on the transition from VZ progenitors to IPCs and activation of proliferation of the IPCs in the cortex during late gestational stages.

  14. Bioengineering of Improved Biomaterials Coatings for Extracorporeal Circulation Requires Extended Observation of Blood-Biomaterial Interaction under Flow


    Stevens, Kris N. J.; Aldenhoff, Yvette B. J.; van der Veen, Frederik H; Maessen, Jos G.; Leo H. Koole


    Extended use of cardiopulmonary bypass (CPB) systems is often hampered by thrombus formation and infection. Part of these problems relates to imperfect hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces with genuine long-term hemocompatibility is essentially virgin territory in biomaterials science. For example, most experiments with the well-known Chandler loop model, for evaluation of blood-biomaterial interactions under flow, have be...

  15. The case study of biomaterials and biominerals (United States)

    Del Hoyo Martínez, Carmen


    The teaching of biomaterials as case study by on-line platform , susceptible to develop both individually and in groups, got different objectives proposed by the European Higher Education System, among which include: participate actively in the teaching-learning process by students, interpreting situations, adapt processes and solutions. It also improves oral and written communication, analytical skills and synthesis and also the ability to think critically. Biomaterials have their origin in biominerals. These are solid inorganic compounds of defined structure, consisting of molecular control mechanisms that operate in biological systems. Its main functions are: structural support, a reservoir of essential elements, sensors, mechanical protection and storage of toxic elements. Following the demand of materials compatible with certain functional systems of our body, developed biomaterials. Always meet the condition of biocompatibility. Should be tolerated by the body and do not provoke rejection. This involves a comprehensive study of physiological conditions and the anatomy of the body where a biomaterial has to be implemented. The possibility of generating new materials from biominerals has a major impact in medicine and other fields could reach as geology, construction, crystallography, etc. While the study of these issues is in its infancy today, can be viewed as an impact on the art and future technology. Planning case study that students would prepare its report for discussion in subgroups. Occurs then the pooling of individual analysis, joint case discussion and adoption by the subgroup of a consensual solution to the problem. The teacher as facilitator and coordinator of the final case analysis, sharing leads to group-wide class and said the unanimous decision reached by the students and gives his opinion on the resolution of the case. REFERENCES D.P. Ausubel. Psicología Educativa. Un punto de vista cognoscitivo. Trillas. Ed. 1983. E.W. Eisner. Procesos

  16. Biomaterials and tissue engineering in reconstructive surgery

    Indian Academy of Sciences (India)

    D F Williams


    This paper provides an account of the rationale for the development of implantable medical devices over the last half-century and explains the criteria that have controlled the selection of biomaterials for these critical applications. In spite of some good successes and excellent materials, there are still serious limitations to the performance of implants today, and the paper explains these limitations and develops this theme in order to describe the recent innovations in tissue engineering, which involves a different approach to reconstruction of the body.

  17. Atomic layer deposition of nanoporous biomaterials

    Directory of Open Access Journals (Sweden)

    Roger J Narayan


    Full Text Available Due to its chemical stability, uniform pore size, and high pore density, nanoporous alumina is being investigated for use in biosensing, drug delivery, hemodialysis, and other medical applications. In recent work, we have examined the use of atomic layer deposition for coating the surfaces of nanoporous alumina membranes. Zinc oxide coatings were deposited on nanoporous alumina membranes using atomic layer deposition. The zinc oxide-coated nanoporous alumina membranes demonstrated antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria. These results suggest that atomic layer deposition is an attractive technique for modifying the surfaces of nanoporous alumina membranes and other nanostructured biomaterials.

  18. Optical approach in characterizing dental biomaterials (United States)

    Demoli, Nazif; Vučić, Zlatko; Milat, Ognjen; Gladić, Jadranko; Lovrić, Davorin; Pandurić, Vlatko; Marović, Danijela; Moguš-Milanković, Andrea; Ristić, Mira; Čalogović, Marina; Tarle, Zrinka


    The purpose of this paper is to present the current activities of a research collaborative program between three institutions from Zagreb (School of Dental Medicine, Institute of Physics, and Institute Ruđer Bo\\vsković). Within the scope of this program, it is planned to investigate and find guidelines for the refinement of the properties of dental biomaterials (DBs) and of procedures in restorative dental medicine. It is also planned to identify and model the dominant mechanisms which control polymerization of DBs. The materials to be investigated include methacrylate based composite resins, new composite materials with amorphous calcium phosphate, silorane based composite resins, glass-ionomer cements, and giomer.

  19. Cell reactions with biomaterials: the microscopies

    Directory of Open Access Journals (Sweden)

    Curtis A. S.G.


    Full Text Available The methods and results of optical microscopy that can be used to observe cell reactions to biomaterials are Interference Reflection Microscopy (IRM, Total Internal Reflection Fluorescence Microscopy (TIRFM, Surface Plasmon Resonance Microscopy (SPRM and Forster Resonance Energy Transfer Microscopy (FRETM and Standing Wave Fluorescence Microscopy. The last three are new developments, which have not yet been fully perfected. TIRFM and SPRM are evanescent wave methods. The physics of these methods depend upon optical phenomena at interfaces. All these methods give information on the dimensions of the gap between cell and the substratum to which it is adhering and thus are especially suited to work with biomaterials. IRM and FRETM can be used on opaque surfaces though image interpretation is especially difficult for IRM on a reflecting opaque surface. These methods are compared with several electron microscopical methods for studying cell adhesion to substrata. These methods all yield fairly consistent results and show that the cell to substratum distance on many materials is in the range 5 to 30 nm. The area of contact relative to the total projected area of the cell may vary from a few per cent to close to 100% depending on the cell type and substratum. These methods show that those discrete contact areas well known as focal contacts are frequently present. The results of FRETM suggest that the separation from the substratum even in a focal contact is about 5 nm.

  20. Use of radiation in biomaterials science (United States)

    Benson, Roberto S.


    Radiation is widely used in the biomaterials science for surface modification, sterilization and to improve bulk properties. Radiation is also used to design of biochips, and in situ photopolymerizable of bioadhesives. The energy sources most commonly used in the irradiation of biomaterials are high-energy electrons, gamma radiation, ultraviolet (UV) and visible light. Surface modification involves placement of selective chemical moieties on the surface of a material by chemical reactions to improve biointeraction for cell adhesion and proliferation, hemocompatibility and water absorption. The exposure of a polymer to radiation, especially ionizing radiation, can lead to chain scission or crosslinking with changes in bulk and surface properties. Sterilization by irradiation is designed to inactivate most pathogens from the surface of biomedical devices. An overview of the use of gamma and UV radiation to improve surface tissue compatibility, bulk properties and surface properties for wear resistance, formation of hydrogels and curing dental sealants and bone adhesives is presented. Gamma and vacuum ultraviolet (VUV) irradiated ultrahigh molecular weight polyethylene (UHMWPE) exhibit improvement in surface modulus and hardness. The surface modulus and hardness of UHMWPE showed a dependence on type of radiation, dosage and processing. VUV surface modified e-PTFE vascular grafts exhibit increases in hydrophilicity and improvement towards adhesion of fibrin glue.

  1. Engineering biomolecular microenvironments for cell instructive biomaterials. (United States)

    Custódio, Catarina A; Reis, Rui L; Mano, João F


    Engineered cell instructive microenvironments with the ability to stimulate specific cellular responses are a topic of high interest in the fabrication and development of biomaterials for application in tissue engineering. Cells are inherently sensitive to the in vivo microenvironment that is often designed as the cell "niche." The cell "niche" comprising the extracellular matrix and adjacent cells, influences not only cell architecture and mechanics, but also cell polarity and function. Extensive research has been performed to establish new tools to fabricate biomimetic advanced materials for tissue engineering that incorporate structural, mechanical, and biochemical signals that interact with cells in a controlled manner and to recapitulate the in vivo dynamic microenvironment. Bioactive tunable microenvironments using micro and nanofabrication have been successfully developed and proven to be extremely powerful to control intracellular signaling and cell function. This Review is focused in the assortment of biochemical signals that have been explored to fabricate bioactive cell microenvironments and the main technologies and chemical strategies to encode them in engineered biomaterials with biological information.

  2. Grand challenge in Biomaterials-wound healing (United States)

    Salamone, Joseph C.; Salamone, Ann Beal; Swindle-Reilly, Katelyn; Leung, Kelly Xiaoyu-Chen; McMahon, Rebecca E.


    Providing improved health care for wound, burn and surgical patients is a major goal for enhancing patient well-being, in addition to reducing the high cost of current health care treatment. The introduction of new and novel biomaterials and biomedical devices is anticipated to have a profound effect on the future improvement of many deleterious health issues. This publication will discuss the development of novel non-stinging liquid adhesive bandages in healthcare applications developed by Rochal Industries. The scientists/engineers at Rochal have participated in commercializing products in the field of ophthalmology, including rigid gas permeable contact lenses, soft hydrogel contact lenses, silicone hydrogel contact lenses, contact lens care solutions and cleaners, intraocular lens materials, intraocular controlled drug delivery, topical/intraocular anesthesia, and in the field of wound care, as non-stinging, spray-on liquid bandages to protect skin from moisture and body fluids and medical adhesive-related skin injuries. Current areas of entrepreneurial activity at Rochal Industries pertain to the development of new classes of biomaterials for wound healing, primarily in regard to microbial infection, chronic wound care, burn injuries and surgical procedures, with emphasis on innovation in product creation, which include cell-compatible substrates/scaffolds for wound healing, antimicrobial materials for opportunistic pathogens and biofilm reduction, necrotic wound debridement, scar remediation, treatment of diabetic ulcers, amelioration of pressure ulcers, amelioration of neuropathic pain and adjuvants for skin tissue substitutes. PMID:27047680

  3. Graphite Oxide to Graphene. Biomaterials to Bionics. (United States)

    Thompson, Brianna C; Murray, Eoin; Wallace, Gordon G


    The advent of implantable biomaterials has revolutionized medical treatment, allowing the development of the fields of tissue engineering and medical bionic devices (e.g., cochlea implants to restore hearing, vagus nerve stimulators to control Parkinson's disease, and cardiac pace makers). Similarly, future materials developments are likely to continue to drive development in treatment of disease and disability, or even enhancing human potential. The material requirements for implantable devices are stringent. In all cases they must be nontoxic and provide appropriate mechanical integrity for the application at hand. In the case of scaffolds for tissue regeneration, biodegradability in an appropriate time frame may be required, and for medical bionics electronic conductivity is essential. The emergence of graphene and graphene-family composites has resulted in materials and structures highly relevant to the expansion of the biomaterials inventory available for implantable medical devices. The rich chemistries available are able to ensure properties uncovered in the nanodomain are conveyed into the world of macroscopic devices. Here, the inherent properties of graphene, along with how graphene or structures containing it interface with living cells and the effect of electrical stimulation on nerves and cells, are reviewed.

  4. Biomaterials for integration with 3-D bioprinting. (United States)

    Skardal, Aleksander; Atala, Anthony


    Bioprinting has emerged in recent years as an attractive method for creating 3-D tissues and organs in the laboratory, and therefore is a promising technology in a number of regenerative medicine applications. It has the potential to (i) create fully functional replacements for damaged tissues in patients, and (ii) rapidly fabricate small-sized human-based tissue models, or organoids, for diagnostics, pathology modeling, and drug development. A number of bioprinting modalities have been explored, including cellular inkjet printing, extrusion-based technologies, soft lithography, and laser-induced forward transfer. Despite the innovation of each of these technologies, successful implementation of bioprinting relies heavily on integration with compatible biomaterials that are responsible for supporting the cellular components during and after biofabrication, and that are compatible with the bioprinting device requirements. In this review, we will evaluate a variety of biomaterials, such as curable synthetic polymers, synthetic gels, and naturally derived hydrogels. Specifically we will describe how they are integrated with the bioprinting technologies above to generate bioprinted constructs with practical application in medicine.

  5. Biomaterial surface proteomic signature determines interaction with epithelial cells. (United States)

    Abdallah, Mohamed-Nur; Tran, Simon D; Abughanam, Ghada; Laurenti, Marco; Zuanazzi, David; Mezour, Mohamed A; Xiao, Yizhi; Cerruti, Marta; Siqueira, Walter L; Tamimi, Faleh


    Cells interact with biomaterials indirectly through extracellular matrix (ECM) proteins adsorbed onto their surface. Accordingly, it could be hypothesized that the surface proteomic signature of a biomaterial might determine its interaction with cells. Here, we present a surface proteomic approach to test this hypothesis in the specific case of biomaterial-epithelial cell interactions. In particular, we determined the surface proteomic signature of different biomaterials exposed to the ECM of epithelial cells (basal lamina). We revealed that the biomaterial surface chemistry determines the surface proteomic profile, and subsequently the interaction with epithelial cells. In addition, we found that biomaterials with surface chemistries closer to that of percutaneous tissues, such as aminated PMMA and aminated PDLLA, promoted higher selective adsorption of key basal lamina proteins (laminins, nidogen-1) and subsequently improved their interactions with epithelial cells. These findings suggest that mimicking the surface chemistry of natural percutaneous tissues can improve biomaterial-epithelial integration, and thus provide a rationale for the design of improved biomaterial surfaces for skin regeneration and percutaneous medical devices.

  6. Innate Immunity and Biomaterials at the Nexus: Friends or Foes

    Directory of Open Access Journals (Sweden)

    Susan N. Christo


    Full Text Available Biomaterial implants are an established part of medical practice, encompassing a broad range of devices that widely differ in function and structural composition. However, one common property amongst biomaterials is the induction of the foreign body response: an acute sterile inflammatory reaction which overlaps with tissue vascularisation and remodelling and ultimately fibrotic encapsulation of the biomaterial to prevent further interaction with host tissue. Severity and clinical manifestation of the biomaterial-induced foreign body response are different for each biomaterial, with cases of incompatibility often associated with loss of function. However, unravelling the mechanisms that progress to the formation of the fibrotic capsule highlights the tightly intertwined nature of immunological responses to a seemingly noncanonical “antigen.” In this review, we detail the pathways associated with the foreign body response and describe possible mechanisms of immune involvement that can be targeted. We also discuss methods of modulating the immune response by altering the physiochemical surface properties of the biomaterial prior to implantation. Developments in these areas are reliant on reproducible and effective animal models and may allow a “combined” immunomodulatory approach of adapting surface properties of biomaterials, as well as treating key immune pathways to ultimately reduce the negative consequences of biomaterial implantation.

  7. Application of a fuzzy neural network model in predicting polycyclic aromatic hydrocarbon-mediated perturbations of the Cyp1b1 transcriptional regulatory network in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Larkin, Andrew [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Department of Statistics, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Krueger, Sharon K. [Superfund Research Center, Oregon State University (United States); Linus Pauling Institute, Oregon State University (United States); Tilton, Susan C.; Waters, Katrina M. [Superfund Research Center, Oregon State University (United States); Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Williams, David E., E-mail: [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Linus Pauling Institute, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Baird, William M. [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States)


    Polycyclic aromatic hydrocarbons (PAHs) are present in the environment as complex mixtures with components that have diverse carcinogenic potencies and mostly unknown interactive effects. Non-additive PAH interactions have been observed in regulation of cytochrome P450 (CYP) gene expression in the CYP1 family. To better understand and predict biological effects of complex mixtures, such as environmental PAHs, an 11 gene input-1 gene output fuzzy neural network (FNN) was developed for predicting PAH-mediated perturbations of dermal Cyp1b1 transcription in mice. Input values were generalized using fuzzy logic into low, medium, and high fuzzy subsets, and sorted using k-means clustering to create Mamdani logic functions for predicting Cyp1b1 mRNA expression. Model testing was performed with data from microarray analysis of skin samples from FVB/N mice treated with toluene (vehicle control), dibenzo[def,p]chrysene (DBC), benzo[a]pyrene (BaP), or 1 of 3 combinations of diesel particulate extract (DPE), coal tar extract (CTE) and cigarette smoke condensate (CSC) using leave-one-out cross-validation. Predictions were within 1 log{sub 2} fold change unit of microarray data, with the exception of the DBC treatment group, where the unexpected down-regulation of Cyp1b1 expression was predicted but did not reach statistical significance on the microarrays. Adding CTE to DPE was predicted to increase Cyp1b1 expression, whereas adding CSC to CTE and DPE was predicted to have no effect, in agreement with microarray results. The aryl hydrocarbon receptor repressor (Ahrr) was determined to be the most significant input variable for model predictions using back-propagation and normalization of FNN weights. - Highlights: ► Tested a model to predict PAH mixture-mediated changes in Cyp1b1 expression ► Quantitative predictions in agreement with microarrays for Cyp1b1 induction ► Unexpected difference in expression between DBC and other treatments predicted ► Model predictions

  8. Study on MCP-1 related to inflammation induced by biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Ding Tingting [Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University/Shanghai Biomaterials Research and Testing Center, Shanghai 200023 (China); Sun Jiao [Shanghai Key Laboratory of Stomatology, Shanghai 200023 (China); Zhang Ping, E-mail: [School of Life Science, East China Normal University, Shanghai 200062 (China)


    The study of inflammation is important for understanding the reaction between biomaterials and the human body, in particular, the interaction between biomaterials and immune system. In the current study, rat macrophages were induced by multiple biomaterials with different biocompatibilities, including polyvinyl chloride (PVC) containing 8% of organic tin, a positive control material with cellular toxicity. Human umbilical vein endothelial cells (ECV-304), cultured with PRMI-1640, were detached from cells cultured with the supernatant of macrophages containing TNF-alpha and IL-1beta because of stimulation by biomaterials. The cells were then treated with different biomaterials. Then both TNF-alpha and IL-1beta in macrophages were detected by ELISA. Levels of monocyte chemoattractant protein-1 (MCP-1) were measured by RT-PCR. The results suggested that the expression of TNF-alpha and IL-1beta was elevated by polytetrafluoroethylene (PTFE), polylactic-co-glycolic acid (PLGA) and American NPG alloy (p < 0.001). The level of MCP-1 cultured in supernatant of macrophages was higher than in PRMI-1640 with the same biomaterials. And the exposure to PTFE, PLGA and NPG resulted in the high expression of MCP-1 (p < 0.001) following cytokine stimulation. MCP-1 was also significantly expressed in beta-tricalcium phosphate (beta-TCP) and calcium phosphate cement samples (CPC) (p < 0.01). Thus, TNF-alpha, IL-1beta and MCP-1 had played an important role in the immune reaction induced by biomaterials and there was a close relationship between the expression of cytokines and biomcompatibility of biomaterials. Furthermore, these data suggested that MCP-1 was regulated by TNF-alpha and IL-1beta, and activated by both cytokines and biomaterials. The data further suggested that the expression of MCP-1 could be used as a marker to indicate the degree of immune reaction induced by biomaterials.

  9. Biomaterial design for specific cellular interactions: Role of surface functionalization and geometric features (United States)

    Kolhar, Poornima

    The areas of drug delivery and tissue engineering have experienced extraordinary growth in recent years with the application of engineering principles and their potential to support and improve the field of medicine. The tremendous progress in nanotechnology and biotechnology has lead to this explosion of research and development in biomedical applications. Biomaterials can now be engineered at a nanoscale and their specific interactions with the biological tissues can be modulated. Various design parameters are being established and researched for design of drug-delivery carriers and scaffolds to be implanted into humans. Nanoparticles made from versatile biomaterial can deliver both small-molecule drugs and various classes of bio-macromolecules, such as proteins and oligonucleotides. Similarly in the field of tissue engineering, current approaches emphasize nanoscale control of cell behavior by mimicking the natural extracellular matrix (ECM) unlike, traditional scaffolds. Drug delivery and tissue engineering are closely connected fields and both of these applications require materials with exceptional physical, chemical, biological, and biomechanical properties to provide superior therapy. In the current study the surface functionalization and the geometric features of the biomaterials has been explored. In particular, a synthetic surface for culture of human embryonic stem cells has been developed, demonstrating the importance of surface functionalization in maintaining the pluripotency of hESCs. In the second study, the geometric features of the drug delivery carriers are investigated and the polymeric nanoneedles mediated cellular permeabilization and direct cytoplasmic delivery is reported. In the third study, the combined effect of surface functionalization and geometric modification of carriers for vascular targeting is enunciated. These studies illustrate how the biomaterials can be designed to achieve various cellular behaviors and control the

  10. Numerical Modeling of Porous Structure of Biomaterial and Fluid Flowing Through Biomaterial

    Institute of Scientific and Technical Information of China (English)


    A Cellular Automata model of simulating body fluid flowing into porous bioceramic implants generated with stochastic methods is described, of which main parameters and evolvement rule are determined in terms of flow behavior of body fluid in porous biomaterials. The model is implemented by GUI( Graphical User Interface) program in MATLAB, and the results of numerical modeling show that the body fluid percolation is related to the size of pores and porosity.

  11. [Development of biodegradable magnesium-based biomaterials]. (United States)

    Zhu, Shengfa; Xu, Li; Huang, Nan


    Magnesium is a macroelement which is indispensable to human bodies. As a lightweight metal with high specific strength and favorable biocompatibility, magnesium and its alloys have been introduced in the field of biomedical materials research and have a broad application prospect. It is possible to develop new type of biodegradable medical magnesium alloys by use of the poor corrosion resistance of magnesium. Bioabsorbable magnesium stents implanted in vivo could mechanically support the vessel in a short term, effectly prevent the acute coronary occlusion and in-stent restenosis, and then be gradully biodegraded and completely absorbed in a long term. Osteoconductive bioactivity in magnesium-based alloys could promote the apposition growth of bone tissue. This paper reviews the progress of magnesium and its alloys applied in bone tissue and cardiovascular stents, and the prospect of the future research of magnesium-based biomaterials is discussed.

  12. Toward biomaterial-based implantable photonic devices (United States)

    Humar, Matjaž; Kwok, Sheldon J. J.; Choi, Myunghwan; Yetisen, Ali K.; Cho, Sangyeon; Yun, Seok-Hyun


    Optical technologies are essential for the rapid and efficient delivery of health care to patients. Efforts have begun to implement these technologies in miniature devices that are implantable in patients for continuous or chronic uses. In this review, we discuss guidelines for biomaterials suitable for use in vivo. Basic optical functions such as focusing, reflection, and diffraction have been realized with biopolymers. Biocompatible optical fibers can deliver sensing or therapeutic-inducing light into tissues and enable optical communications with implanted photonic devices. Wirelessly powered, light-emitting diodes (LEDs) and miniature lasers made of biocompatible materials may offer new approaches in optical sensing and therapy. Advances in biotechnologies, such as optogenetics, enable more sophisticated photonic devices with a high level of integration with neurological or physiological circuits. With further innovations and translational development, implantable photonic devices offer a pathway to improve health monitoring, diagnostics, and light-activated therapies.

  13. Tribological characteristics of dental metal biomaterials

    Directory of Open Access Journals (Sweden)

    Walczak Mariusz


    Full Text Available The paper is a report of the examination of the tribological wear characteristics of certain dental metal biomaterials. In the study, tests were undertaken on the following materials: 316L steel, NiCrMo alloy, technically pure titanium (ASTM-grade 2 and Ti6Al4V ELI alloy (ASTM-grade 5. The tribological tests were performed in artificial saliva to determine the coefficient of friction and wear factor; the traces of wear were then ascertained through SEM. The significance of variations in the wear factor, was subsequently assessed by the U Mann-Whitney test. The resistance to wear in the ball-on-disc test under in vitro conditions was observed for the tested materials in the following order: NiCrMo>316L>Ti6Al4V>Ti grade 2.

  14. Chitosan dan Aplikasi Klinisnya Sebagai Biomaterial

    Directory of Open Access Journals (Sweden)

    Bambang Irawan


    Full Text Available The development of new materials with both organic and inorganic structures is of great interest to obtain special material properties. Chitosan [2-amino-2-deoxy-D-glucan] can be obtained by N-deacetylation of chitin. Chitin is the second most abundant biopolymer in nature and the supporting material of crustaceans, insects, fungi etc. Chitosan is unique polysaccharide and has been widely used in various biomedical application due to its biocompatibility, low toxicity, biodegradability, non-immunogenic and non-carcinogenic character. In the past few years, chitosan and some of its modifications have been reported for use in biomedical applications such as artificial skin, wound dressing, anticoagulant, suture, drug delivery, vaccine carrier and dietary fibers. Recently, the use of chitosan and its derivatives has received much attention as temporary scaffolding to promotie mineralization or stimulate endochodral ossification. This article aims to give a broad overview of chitosan and its clinical applications as biomaterial.

  15. Fiber from ramie plant (Boehmeria nivea): A novel suture biomaterial

    Energy Technology Data Exchange (ETDEWEB)

    Kandimalla, Raghuram; Kalita, Sanjeeb; Choudhury, Bhaswati [Drug discovery laboratory, Institute of Advanced Study in Science and Technology, Guwahati, Assam 781035 (India); Devi, Dipali [Seri biotech laboratory, Institute of Advanced Study in Science and Technology, Guwahati, Assam 781035 (India); Kalita, Dhaneswar [Government Ayurvedic College and Hospital, Jalukbari, Guwahati, Assam 781014 (India); Kalita, Kasturi [Department of Pathology, Hayat Hospital, Guwahati, Assam 781034 (India); Dash, Suvakanta [Girijananda Chowdhury Institute of pharmaceutical science, Azara, Guwahati, Assam 781017 (India); Kotoky, Jibon, E-mail: [Drug discovery laboratory, Institute of Advanced Study in Science and Technology, Guwahati, Assam 781035 (India)


    The quest for developing an ideal suture material prompted our interest to develop a novel suture with advantageous characters to market available ones. From natural origin only silk, cotton and linen fibers are presently available in market as non-absorbable suture biomaterials. In this study, we have developed a novel, cost-effective, and biocompatible suture biomaterial from ramie plant, Boehmeria nivea fiber. Field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and thermo gravimetric analysis (TGA) results revealed the physicochemical properties of raw and degummed ramie fiber, where the former one showed desirable characteristics for suture preparation. The braided multifilament ramie suture prepared from degummed fiber exhibited excellent tensile strength. The suture found to be biocompatible towards human erythrocytes and nontoxic to mammalian cells. The fabricated ramie suture exhibited significant antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus; which can be attributed to the inherent bacteriostatic ability of ramie plant fiber. In vivo wound closure efficacy was evaluated in adult male wister rats by suturing the superficial wound incisions. Within seven days of surgery the wound got completely healed leaving no rash and scar. The role of the ramie suture in complete wound healing was supported by the reduced levels of serum inflammatory mediators. Histopathology studies confirmed the wound healing ability of ramie suture, as rapid synthesis of collagen, connective tissue and other skin adnexal structures were observed within seven days of surgery. Tensile properties, biocompatibility and wound closure efficacy of the ramie suture were comparable with market available BMSF suture. The outcome of this study can drive tremendous possibility for the utilization of ramie plant fiber for

  16. New frontiers in biomaterials research for tissue repair and regeneration

    Institute of Scientific and Technical Information of China (English)

    Huiling Liu; Haoran Liu; Aaron Clasky; Huilin Yang; Lei Yang


    The field of biomaterials has recently emerged to augment or replace lost or damaged tissues and organs due to the human body’s limited ability to self-heal large defects. Historically, metallic components, polymers, ceramics, and composite materials were utilized as synthetic materials along with natural materials to assist in therapy. Various novel biomaterials were developed to respond to a significant amount of new medical challenges in the past decade. Therefore, there is a need to review these newly developed biomaterials and their potential to improve tissue repair and regeneration in a variety of applications. Here, we briefly review the different strategies and attempts to use novel biomaterials, including self-assembled and macromolecular biomaterials, hydrogels, metamaterials, decellularized tissues, and biomaterials obtained via synthetic biology, used either for tissue repair and regeneration or for therapeutic use by exploiting other mechanisms of healing. All these methods aim to create functional materials, devices, systems, and/or organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. This review details the various methods and introduces the applications of these biomaterials in tissue repair and regeneration, especially for bone, nerve, and skin applications.


    NARCIS (Netherlands)



    Studying the tissue-biomaterial interface at the ultrastructural level is not without problems. Dissolution of the biomaterial in one of the dehydration or embedding media causes holes and shatter during sectioning or dislodgement of the biomaterial. The fine tuning of the hardness of both biomateri

  18. Biomaterial-Associated Infection : Locating the Finish Line in the Race for the Surface

    NARCIS (Netherlands)

    Busscher, Henk J.; van der Mei, Henny C.; Subbiahdoss, Guruprakash; Jutte, Paul C.; van den Dungen, Jan J. A. M.; Zaat, Sebastian A. J.; Schultz, Marcus J.; Grainger, David W.


    Biomaterial-associated infections occur on both permanent implants and temporary devices for restoration or support of human functions. Despite increasing use of biomaterials in an aging society, comparatively few biomaterials have been designed that effectively reduce the incidence of biomaterial-a

  19. Mechanical and biological properties of keratose biomaterials. (United States)

    de Guzman, Roche C; Merrill, Michelle R; Richter, Jillian R; Hamzi, Rawad I; Greengauz-Roberts, Olga K; Van Dyke, Mark E


    The oxidized form of extractable human hair keratin proteins, commonly referred to as keratose, is gaining interest as a biomaterial for multiple tissue engineering studies including those directed toward peripheral nerve, spinal cord, skin, and bone regeneration. Unlike its disulfide cross-linked counterpart, kerateine, keratose does not possess a covalently cross-linked network structure and consequently displays substantially different characteristics. In order to understand its mode(s) of action and potential for clinical translatability, detailed characterization of the composition, physical properties, and biological responses of keratose biomaterials are needed. Keratose was obtained from end-cut human hair fibers by peracetic acid treatment, followed by base extraction, and subsequent dialysis. Analysis of lyophilized keratose powder determined that it contains 99% proteins by mass with amino acid content similar to human hair cortex. Metallic elements were also found in minute quantities. Protein oxidation led to disulfide bond cleavage and drastic reduction of free thiols due to conversion of sulfhydryl to sulfonic acid, chain fragmentation, and amino acid modifications. Mass spectrometry identified the major protein constituents as a heterogeneous mixture of 15 hair keratins (type I: K31-35 and K37-39, and type II: K81-86) with small amounts of epithelial keratins which exist in monomeric, dimeric, multimeric, and even degraded forms. Re-hydration with PBS enabled molecular assembly into an elastic solid-like hydrogel. Highly-porous scaffolds formed by lyophilization of the gel had the compression behavior of a cellular foam material and reverted back to gel upon wetting. Cytotoxicity assays showed that the EC50 for various cell lines were attained at 8-10 mg/mL keratose, indicating the non-toxic nature of the material. Implantation in mouse subcutaneous tissue pockets demonstrated that keratose resorption follows a rectangular hyperbolic regression

  20. Investigation of potential injectable polymeric biomaterials for bone regeneration. (United States)

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


    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.

  1. Brillouin microspectroscopy of nanostructured biomaterials: photonics assisted tailoring mechanical properties (United States)

    Meng, Zhaokai; Jaiswal, Manish K.; Chitrakar, Chandani; Thakur, Teena; Gaharwar, Akhilesh K.; Yakovlev, Vladislav V.


    Developing new biomaterials is essential for the next-generation of materials for bioenergy, bioelectronics, basic biology, medical diagnostics, cancer research, and regenerative medicine. Specifically, recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. The physical properties of nanocomposite biomaterials, including elasticity and viscosity, play key roles in controlling cell fate, which underlines therapeutic success. Conventional mechanical tests, including uniaxial compression and tension, dynamic mechanical analysis and shear rheology, require mechanical forces to be directly exerted onto the sample and therefore may not be suitable for in situ measurements or continuous monitoring of mechanical stiffness. In this study, we employ spontaneous Brillouin spectroscopy as a viscoelasticity-specific probing technique. We utilized a Brillouin spectrometer to characterize biomaterial's microscopic elasticity and correlated those with conventional mechanical tests (e.g., rheology).

  2. Numerical Simulation of thePorous Structure of Biomaterials

    Institute of Scientific and Technical Information of China (English)

    WANGHui-min; YANYu-hua; LIShi-pu


    Porous biomaterials are widely used as bone replacement materials because of thers high biocompatibility and osteoconductivity property. Understanding of their porous structure (i. e. geometrical and topological characteristic) and studying how to the body fluid flow through them are essential to investigate thed egradation behaviour at the surface-liquid interface. This research develops a numerical model to simulate the porous structure of biomaterials based on the stochastic approach in pore size distribution and interconnectivity.

  3. A Multidisciplined Teaching Reform of Biomaterials Course for Undergraduate Students (United States)

    Li, Xiaoming; Zhao, Feng; Pu, Fang; Liu, Haifeng; Niu, Xufeng; Zhou, Gang; Li, Deyu; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Watari, Fumio


    The biomaterials science has advanced in a high speed with global science and technology development during the recent decades, which experts predict to be more obvious in the near future with a more significant position for medicine and health care. Although the three traditional subjects, such as medical science, materials science and biology that act as a scaffold to support the structure of biomaterials science, are still essential for the research and education of biomaterials, other subjects, such as mechanical engineering, mechanics, computer science, automatic science, nanotechnology, and Bio-MEMS, are playing more and more important roles in the modern biomaterials science development. Thus, the research and education of modern biomaterials science should require a logical integration of the interdisciplinary science and technology, which not only concerns medical science, materials science and biology, but also includes other subjects that have been stated above. This article focuses on multidisciplinary nature of biomaterials, the awareness of which is currently lacking in the education at undergraduate stage. In order to meet this educational challenge, we presented a multidisciplinary course that referred to not only traditional sciences, but also frontier sciences and lasted for a whole academic year for senior biomaterials undergraduate students with principles of a better understanding of the modern biomaterials science and meeting the requirements of the future development in this area. The course has been shown to gain the recognition of the participants by questionaries and specific "before and after" comments and has also gained high recognition and persistent supports from our university. The idea of this course might be also fit for the education and construction of some other disciplines.

  4. Polyelectrolyte Biomaterial Interactions Provide Nanoparticulate Carrier for Oral Insulin Delivery


    Reis, Catarina Pinto; Ribeiro, António J; Veiga, Francisco; Neufeld, Ronald J; Damgé, Christiane


    Nanospheres are being developed for the oral delivery of peptide-based drugs such as insulin. Mucoadhesive, biodegradable, biocompatible, and acid-protective biomaterials are described using a combination of natural polyelectrolytes, with particles formulated through nanoemulsion dispersion followed by triggered in situgel complexation. Biomaterials meeting these criteria include alginate, dextran, chitosan, and albumin in which alginate/dextran forms the core matrix complexed with chitosan a...

  5. Metals and alloys in the function of biomaterials

    Directory of Open Access Journals (Sweden)

    Dejan I. Tanikić


    Full Text Available Biomaterials are natural or synthetic materials, used for guidance, maintaining or replacing the function of the human body's live tissues. Metal biomaterials are mainly used for replacing broken or damaged hard tissues such as bones, because of their high strength, toughness and corrosion resistance. The most frequently used metals are stainless steels, cobalt based alloys as well as titanium and its alloys. A review of the metals and alloys mostly used in biomedicine are presented in this paper.

  6. Additive Manufacturing of Biomaterials, Tissues, and Organs. (United States)

    Zadpoor, Amir A; Malda, Jos


    The introduction of additive manufacturing (AM), often referred to as three-dimensional (3D) printing, has initiated what some believe to be a manufacturing revolution, and has expedited the development of the field of biofabrication. Moreover, recent advances in AM have facilitated further development of patient-specific healthcare solutions. Customization of many healthcare products and services, such as implants, drug delivery devices, medical instruments, prosthetics, and in vitro models, would have been extremely challenging-if not impossible-without AM technologies. The current special issue of the Annals of Biomedical Engineering presents the latest trends in application of AM techniques to healthcare-related areas of research. As a prelude to this special issue, we review here the most important areas of biomedical research and clinical practice that have benefited from recent developments in additive manufacturing techniques. This editorial, therefore, aims to sketch the research landscape within which the other contributions of the special issue can be better understood and positioned. In what follows, we briefly review the application of additive manufacturing techniques in studies addressing biomaterials, (re)generation of tissues and organs, disease models, drug delivery systems, implants, medical instruments, prosthetics, orthotics, and AM objects used for medical visualization and communication.

  7. Atomic layer deposition of nanoporous biomaterials.

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, R. J.; Adiga, S. P.; Pellin, M. J.; Curtiss, L. A.; Stafslien, S.; Chisholm, B.; Monteiro-Riviere, N. A.; Brigmon, R. L.; Elam, J. W.; Univ. of North Carolina; North Carolina State Univ.; Eastman Kodak Co.; North Dakota State Univ.; SRL


    Due to its chemical stability, uniform pore size, and high pore density, nanoporous alumina is being investigated for use in biosensing, drug delivery, hemodialysis, and other medical applications. In recent work, we have examined the use of atomic layer deposition for coating the surfaces of nanoporous alumina membranes. Zinc oxide coatings were deposited on nanoporous alumina membranes using atomic layer deposition. The zinc oxide-coated nanoporous alumina membranes demonstrated antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria. These results suggest that atomic layer deposition is an attractive technique for modifying the surfaces of nanoporous alumina membranes and other nanostructured biomaterials. Nanoporous alumina, also known as anodic aluminum oxide (AAO), is a nanomaterial that exhibits several unusual properties, including high pore densities, straight pores, small pore sizes, and uniform pore sizes. In 1953, Keller et al. showed that anodizing aluminum in acid electrolytes results in a thick layer of nearly cylindrical pores, which are arranged in a close-packed hexagonal cell structure. More recently, Matsuda & Fukuda demonstrated preparation of highly ordered platinum and gold nanohole arrays using a replication process. In this study, a negative structure of nanoporous alumina was initially fabricated and a positive structure of a nanoporous metal was subsequently fabricated. Over the past fifteen years, nanoporous alumina membranes have been used as templates for growth of a variety of nanostructured materials, including nanotubes, nanowires, nanorods, and nanoporous membranes.

  8. Modifying plants for biofuel and biomaterial production. (United States)

    Furtado, Agnelo; Lupoi, Jason S; Hoang, Nam V; Healey, Adam; Singh, Seema; Simmons, Blake A; Henry, Robert J


    The productivity of plants as biofuel or biomaterial crops is established by both the yield of plant biomass per unit area of land and the efficiency of conversion of the biomass to biofuel. Higher yielding biofuel crops with increased conversion efficiencies allow production on a smaller land footprint minimizing competition with agriculture for food production and biodiversity conservation. Plants have traditionally been domesticated for food, fibre and feed applications. However, utilization for biofuels may require the breeding of novel phenotypes, or new species entirely. Genomics approaches support genetic selection strategies to deliver significant genetic improvement of plants as sources of biomass for biofuel manufacture. Genetic modification of plants provides a further range of options for improving the composition of biomass and for plant modifications to assist the fabrication of biofuels. The relative carbohydrate and lignin content influences the deconstruction of plant cell walls to biofuels. Key options for facilitating the deconstruction leading to higher monomeric sugar release from plants include increasing cellulose content, reducing cellulose crystallinity, and/or altering the amount or composition of noncellulosic polysaccharides or lignin. Modification of chemical linkages within and between these biomass components may improve the ease of deconstruction. Expression of enzymes in the plant may provide a cost-effective option for biochemical conversion to biofuel.

  9. Impact of silk biomaterial structure on proteolysis. (United States)

    Brown, Joseph; Lu, Chia-Li; Coburn, Jeannine; Kaplan, David L


    The goal of this study was to determine the impact of silk biomaterial structure (e.g. solution, hydrogel, film) on proteolytic susceptibility. In vitro enzymatic degradation of silk fibroin hydrogels and films was studied using a variety of proteases, including proteinase K, protease XIV, α-chymotrypsin, collagenase, matrix metalloproteinase-1 (MMP-1) and MMP-2. Hydrogels were used to assess bulk degradation while films were used to assess surface degradation. Weight loss, secondary structure determined by Fourier transform infrared spectroscopy and degradation products analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used to evaluate degradation over 5 days. Silk films were significantly degraded by proteinase K, while silk hydrogels were degraded more extensively by protease XIV and proteinase K. Collagenase preferentially degraded the β-sheet content in hydrogels while protease XIV and α-chymotrypsin degraded the amorphous structures. MMP-1 and MMP-2 degraded silk fibroin in solution, resulting in a decrease in peptide fragment sizes over time. The link between primary sequence mapping with protease susceptibility provides insight into the role of secondary structure in impacting proteolytic access by comparing solution vs. solid state proteolytic susceptibility.

  10. Advancing the field of 3D biomaterial printing. (United States)

    Jakus, Adam E; Rutz, Alexandra L; Shah, Ramille N


    3D biomaterial printing has emerged as a potentially revolutionary technology, promising to transform both research and medical therapeutics. Although there has been recent progress in the field, on-demand fabrication of functional and transplantable tissues and organs is still a distant reality. To advance to this point, there are two major technical challenges that must be overcome. The first is expanding upon the limited variety of available 3D printable biomaterials (biomaterial inks), which currently do not adequately represent the physical, chemical, and biological complexity and diversity of tissues and organs within the human body. Newly developed biomaterial inks and the resulting 3D printed constructs must meet numerous interdependent requirements, including those that lead to optimal printing, structural, and biological outcomes. The second challenge is developing and implementing comprehensive biomaterial ink and printed structure characterization combined with in vitro and in vivo tissue- and organ-specific evaluation. This perspective outlines considerations for addressing these technical hurdles that, once overcome, will facilitate rapid advancement of 3D biomaterial printing as an indispensable tool for both investigating complex tissue and organ morphogenesis and for developing functional devices for a variety of diagnostic and regenerative medicine applications.

  11. Neural differentiation of brain-derived neurotrophic factor-expressing human umbilical cord blood-derived mesenchymal stem cells in culture via TrkB-mediated ERK and β-catenin phosphorylation and following transplantation into the developing brain. (United States)

    Lim, Jung Yeon; Park, Sang In; Kim, Seong Muk; Jun, Jin Ae; Oh, Ji Hyeon; Ryu, Chung Hun; Jeong, Chang Hyun; Park, Sun Hwa; Park, Soon A; Oh, Wonil; Chang, Jong Wook; Jeun, Sin-Soo


    The ability of mesenchymal stem cells (MSCs) to differentiate into neural cells makes them potential replacement therapeutic candidates in neurological diseases. Presently, overexpression of brain-derived neurotrophic factor (BDNF), which is crucial in the regulation of neural progenitor cell differentiation and maturation during development, was sufficient to convert the mesodermal cell fate of human umbilical cord blood-derived MSCs (hUCB-MSCs) into a neuronal fate in culture, in the absence of specialized induction chemicals. BDNF overexpressing hUCB-MSCs (MSCs-BDNF) yielded an increased number of neuron-like cells and, surprisingly, increased the expression of neuronal phenotype markers in a time-dependent manner compared with control hUCB-MSCs. In addition, MSCs-BDNF exhibited a decreased labeling for MSCs-related antigens such as CD44, CD73, and CD90, and decreased potential to differentiate into mesodermal lineages. Phosphorylation of the receptor tyrosine kinase B (TrkB), which is a receptor of BDNF, was increased significantly in MSC-BDNF. BDNF overexpression also increased the phosphorylation of β-catenin and extracellular signal-regulated kinases (ERKs). Inhibition of TrkB availability by treatment with the TrkB-specific inhibitor K252a blocked the BDNF-stimulated phosphorylation of β-catenin and ERKs, indicating the involvement of both the β-catenin and ERKs signals in the BDNF-stimulated and TrkB-mediated neural differentiation of hUCB-MSCs. Reduction of β-catenin availability using small interfering RNA-mediated gene silencing inhibited ERKs phosphorylation. However, β-catenin activation was maintained. In addition, inhibition of β-catenin and ERKs expression levels abrogated the BDNF-stimulated upregulation of neuronal phenotype markers. Furthermore, MSC-BDNF survived and migrated more extensively when grafted into the lateral ventricles of neonatal mouse brain, and differentiated significantly into neurons in the olfactory bulb and

  12. Preparing polymeric biomaterials using "click" chemistry techniques (United States)

    Lin, Fei

    Significant efforts have been focused on preparing degradable polymeric biomaterials with controllable properties, which have the potential to stimulate specific cellular responses at the molecular level. Click reactions provide a universal tool box to achieve that goal through molecular level design and modification. This dissertation demonstrates multiple methodologies and techniques to develop advanced biomaterials through combining degradable polymers and click chemistry. In my initial work, a novel class of amino acid-based poly(ester urea)s (PEU) materials was designed and prepared for potential applications in bone defect treatment. PEUs were synthesized via interfacial polycondensation, and showed degradability in vivo and possessed mechanical strength superior to conventionally used polyesters. Further mechanical enhancement was achieved after covalent crosslinking with a short peptide crosslinker derived from osteogenic growth peptide (OGP). The in vitro and in an in vivo subcutaneous rat model demonstrated that the OGP-based crosslinkers promoted proliferative activity of cells and accelerated degradation properties of PEUs. As a continuous study, extra efforts were focused on the development of PEUs with functional pendant groups, including alkyne, azide, alkene, tyrosine phenol, and ketone groups. PEUs with Mw exceeding to 100K Da were obtained via interfacial polycondensation, and the concentration of pendent groups was varied using a copolymerization strategy. Electrospinning was used to fabricate PEU nanofiber matrices with mechanical strengths suitable for tissue engineering. A series of biomolecules were conjugated to nanofiber surface following electrospinning using click reactions in aqueous media. The ability to derivatize PEUs with biological motifs using high efficient chemical reactions will significantly expand their use in vitro and in vivo. Based on similar principles, a series of mono- and multifunctionalized polycaprolactone (PCL

  13. Bio-microfluidics: biomaterials and biomimetic designs. (United States)

    Domachuk, Peter; Tsioris, Konstantinos; Omenetto, Fiorenzo G; Kaplan, David L


    Bio-microfluidics applies biomaterials and biologically inspired structural designs (biomimetics) to microfluidic devices. Microfluidics, the techniques for constraining fluids on the micrometer and sub-micrometer scale, offer applications ranging from lab-on-a-chip to optofluidics. Despite this wealth of applications, the design of typical microfluidic devices imparts relatively simple, laminar behavior on fluids and is realized using materials and techniques from silicon planar fabrication. On the other hand, highly complex microfluidic behavior is commonplace in nature, where fluids with nonlinear rheology flow through chaotic vasculature composed from a range of biopolymers. In this Review, the current state of bio-microfluidic materials, designs and applications are examined. Biopolymers enable bio-microfluidic devices with versatile functionalization chemistries, flexibility in fabrication, and biocompatibility in vitro and in vivo. Polymeric materials such as alginate, collagen, chitosan, and silk are being explored as bulk and film materials for bio-microfluidics. Hydrogels offer options for mechanically functional devices for microfluidic systems such as self-regulating valves, microlens arrays and drug release systems, vital for integrated bio-microfluidic devices. These devices including growth factor gradients to study cell responses, blood analysis, biomimetic capillary designs, and blood vessel tissue culture systems, as some recent examples of inroads in the field that should lead the way in a new generation of microfluidic devices for bio-related needs and applications. Perhaps one of the most intriguing directions for the future will be fully implantable microfluidic devices that will also integrate with existing vasculature and slowly degrade to fully recapitulate native tissue structure and function, yet serve critical interim functions, such as tissue maintenance, drug release, mechanical support, and cell delivery.

  14. Methodology of citrate-based biomaterial development and application (United States)

    Tran, M. Richard

    Biomaterials play central roles in modern strategies of regenerative medicine and tissue engineering. Attempts to find tissue-engineered solutions to cure various injuries or diseases have led to an enormous increase in the number of polymeric biomaterials over the past decade. The breadth of new materials arises from the multiplicity of anatomical locations, cell types, and mode of application, which all place application-specific requirements on the biomaterial. Unfortunately, many of the currently available biodegradable polymers are limited in their versatility to meet the wide range of requirements for tissue engineering. Therefore, a methodology of biomaterial development, which is able to address a broad spectrum of requirements, would be beneficial to the biomaterial field. This work presents a methodology of citrate-based biomaterial design and application to meet the multifaceted needs of tissue engineering. We hypothesize that (1) citric acid, a non-toxic metabolic product of the body (Krebs Cycle), can be exploited as a universal multifunctional monomer and reacted with various diols to produce a new class of soft biodegradable elastomers with the flexibility to tune the material properties of the resulting material to meet a wide range of requirements; (2) the newly developed citrate-based polymers can be used as platform biomaterials for the design of novel tissue engineering scaffolding; and (3) microengineering approaches in the form thin scaffold sheets, microchannels, and a new porogen design can be used to generate complex cell-cell and cell-microenvironment interactions to mimic tissue complexity and architecture. To test these hypotheses, we first developed a methodology of citrate-based biomaterial development through the synthesis and characterization of a family of in situ crosslinkable and urethane-doped elastomers, which are synthesized using simple, cost-effective strategies and offer a variety methods to tailor the material properties to

  15. A novel animal model for skin flap prelamination with biomaterials (United States)

    Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun


    Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible.

  16. Characterization of Biomaterials by Soft X-Ray Spectromicroscopy

    Directory of Open Access Journals (Sweden)

    Adam P. Hitchcock


    Full Text Available Synchrotron-based soft X-ray spectromicroscopy techniques are emerging as useful tools to characterize potentially biocompatible materials and to probe protein interactions with model biomaterial surfaces. Simultaneous quantitative chemical analysis of the near surface region of the candidate biomaterial, and adsorbed proteins, peptides or other biological species can be obtained at high spatial resolution via scanning transmission X-ray microscopy (STXM and X-ray photoemission electron microscopy (X-PEEM. Both techniques use near-edge X-ray absorption fine structure (NEXAFS spectral contrast for chemical identification and quantitation. The capabilities of STXM and X-PEEM for the analysis of biomaterials are reviewed and illustrated by three recent studies: (1 characterization of hydrophobic surfaces, including adsorption of fibrinogen (Fg or human serum albumin (HSA to hydrophobic polymeric thin films, (2 studies of HSA adsorption to biodegradable or potentially biocompatible polymers, and (3 studies of biomaterials under fully hydrated conditions. Other recent applications of STXM and X-PEEM to biomaterials are also reviewed.

  17. A novel animal model for skin flap prelamination with biomaterials (United States)

    Zhou, Xianyu; Luo, Xusong; Liu, Fei; Gu, Chuan; Wang, Xi; Yang, Qun; Qian, Yunliang; Yang, Jun


    Several animal models of skin flap construction were reported using biomaterials in a way similar to prefabrication. However, there are few animal model using biomaterials similar to prelamination, another main way of clinical skin flap construction that has been proved to be reliable. Can biomaterials be added in skin flap prelamination to reduce the use of autogenous tissues? Beside individual clinical attempts, animal model is needed for randomized controlled trial to objectively evaluate the feasibility and further investigation. Combining human Acellular Dermal Matrix (hADM) and autologous skin graft, we prelaminated flaps based on inguinal fascia. One, two, three and four weeks later, hADM exhibited a sound revascularization and host cell infiltration. Prelaminated skin flaps were then raised and microsurgically transplanted back to groin region. Except for flaps after one week of prelamination, flaps from other subgroups successfully reconstructed defects. After six to sixteen weeks of transplantation, hADM was proved to being able to maintain its original structure, having a wealth of host tissue cells and achieving full revascularization.To our knowledge, this is the first animal model of prelaminating skin flap with biomaterials. Success of this animal model indicates that novel flap prelamination with biomaterials is feasible. PMID:27659066

  18. Electrospun Nanofibrous Materials for Neural Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Yee-Shuan Lee


    Full Text Available The use of biomaterials processed by the electrospinning technique has gained considerable interest for neural tissue engineering applications. The tissue engineering strategy is to facilitate the regrowth of nerves by combining an appropriate cell type with the electrospun scaffold. Electrospinning can generate fibrous meshes having fiber diameter dimensions at the nanoscale and these fibers can be nonwoven or oriented to facilitate neurite extension via contact guidance. This article reviews studies evaluating the effect of the scaffold’s architectural features such as fiber diameter and orientation on neural cell function and neurite extension. Electrospun meshes made of natural polymers, proteins and compositions having electrical activity in order to enhance neural cell function are also discussed.

  19. Validation of the Osteopenia Sheep Model for Orthopaedic Biomaterial Research

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, C.C.; Cheng, L.;


    Validation of the Osteopenia Sheep Model for Orthopaedic Biomaterial Research +1Ding, M; 2Danielsen, CC; 1Cheng, L; 3Bollen, P; 4Schwarz, P; 1Overgaard, S +1Dept of Orthopaedics O, Odense University Hospital, Denmark, 2Dept of Connective Tissue Biology, University of Aarhus, Denmark, 3Biomedicine...... Lab, University of Southern Denmark, 4Dept of Geriatrics, Glostrup University Hospital, Denmark   Introduction:  Currently, majority orthopaedic prosthesis and biomaterial researches have been based on investigation in normal animals. In most clinical situations, most...... resemble osteoporosis in humans. This study aimed to validate glucocorticoid-induced osteopenia sheep model for orthopaedic implant and biomaterial research. We hypothesized that a 7-month GC treatment together with restricted diet but without OVX would induce osteopenia. Materials and Methods: Eighteen...

  20. The impact of contact angle on the biocompatibility of biomaterials. (United States)

    Menzies, Kara L; Jones, Lyndon


    Biomaterials may be defined as artificial materials that can mimic, store, or come into close contact with living biological cells or fluids and are becoming increasingly popular in the medical, biomedical, optometric, dental, and pharmaceutical industries. Within the ophthalmic industry, the best example of a biomaterial is a contact lens, which is worn by approximately 125 million people worldwide. For biomaterials to be biocompatible, they cannot illicit any type of unfavorable response when exposed to the tissue they contact. A characteristic that significantly influences this response is that related to surface wettability, which is often determined by measuring the contact angle of the material. This article reviews the impact of contact angle on the biocompatibility of tissue engineering substrates, blood-contacting devices, dental implants, intraocular lenses, and contact lens materials.

  1. Bioengineering of Improved Biomaterials Coatings for Extracorporeal Circulation Requires Extended Observation of Blood-Biomaterial Interaction under Flow

    Directory of Open Access Journals (Sweden)

    Kris N. J. Stevens


    Full Text Available Extended use of cardiopulmonary bypass (CPB systems is often hampered by thrombus formation and infection. Part of these problems relates to imperfect hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces with genuine long-term hemocompatibility is essentially virgin territory in biomaterials science. For example, most experiments with the well-known Chandler loop model, for evaluation of blood-biomaterial interactions under flow, have been described for a maximum duration of 2 hours only. This study reports a systematic evaluation of two commercial CPB tubings, each with a hemocompatible coating, and one uncoated control. The experiments comprised (i testing over 5 hours under flow, with human whole blood from 4 different donors; (ii measurement of essential blood parameters of hemocompatibility; (iii analysis of the luminal surfaces by scanning electron microscopy and thrombin generation time measurements. The dataset indicated differences in hemocompatibility of the tubings. Furthermore, it appeared that discrimination between biomaterial coatings can be made only after several hours of blood-biomaterial contact. Platelet counting, myeloperoxidase quantification, and scanning electron microscopy proved to be the most useful methods. These findings are believed to be relevant with respect to the bioengineering of extracorporeal devices that should function in contact with blood for extended time.

  2. Spin-Mediated Consciousness Theory Possible Roles of Oxygen Unpaired Electronic Spins and Neural Membrane Nuclear Spin Ensemble in Memory and Consciousness

    CERN Document Server

    Hu, H; Hu, Huping; Wu, Maoxin


    We postulate that consciousness is connected to quantum mechanical spin since said spin is embedded in the microscopic structure of spacetime and may be more fundamental than spacetime itself. Thus, we theorize that consciousness is connected with the fabric of spacetime through spin. That is, spin is the "pixel" and "antenna" of mind. The unity of mind is achieved by non-local means within the pre-spacetime domain interfaced with spacetime. Human mind is possible because of the particular structures and dynamics of our brain postulated working as follows: The unpaired electronic spins of highly lipid-soluble and rapidly diffusing oxygen molecules extract information from the dynamical neural membranes and communicate said information through strong spin-spin couplings to the nuclear spin ensemble in the membranes for consciousness-related quantum statistical processing which survives decoherence. In turn, the dynamics of the nuclear spin ensemble has effects through spin chemistry on the classical neural act...

  3. Lithotripter shock wave interaction with a bubble near various biomaterials (United States)

    Ohl, S. W.; Klaseboer, E.; Szeri, A. J.; Khoo, B. C.


    Following previous work on the dynamics of an oscillating bubble near a bio-material (Ohl et al 2009 Phys. Med. Biol. 54 6313-36) and the interaction of a bubble with a shockwave (Klaseboer et al 2007 J. Fluid Mech. 593 33-56), the present work concerns the interaction of a gas bubble with a traveling shock wave (such as from a lithotripter) in the vicinity of bio-materials such as fat, skin, muscle, cornea, cartilage, and bone. The bubble is situated in water (to represent a water-like biofluid). The bubble collapses are not spherically symmetric, but tend to feature a high speed jet. A few simulations are performed and compared with available experimental observations from Sankin and Zhong (2006 Phys. Rev. E 74 046304). The collapses of cavitation bubbles (created by laser in the experiment) near an elastic membrane when hit by a lithotripter shock wave are correctly captured by the simulation. This is followed by a more systematic study of the effects involved concerning shockwave bubble biomaterial interactions. If a subsequent rarefaction wave hits the collapsed bubble, it will re-expand to a very large size straining the bio-materials nearby before collapsing once again. It is noted that, for hard bio-material like bone, reflection of the shock wave at the bone—water interface can affect the bubble dynamics. Also the initial size of the bubble has a significant effect. Large bubbles (˜1 mm) will split into smaller bubbles, while small bubbles collapse with a high speed jet in the travel direction of the shock wave. The numerical model offers a computationally efficient way of understanding the complex phenomena involving the interplay of a bubble, a shock wave, and a nearby bio-material.

  4. Biomaterials approaches to treating implant-associated osteomyelitis. (United States)

    Inzana, Jason A; Schwarz, Edward M; Kates, Stephen L; Awad, Hani A


    Orthopaedic devices are the most common surgical devices associated with implant-related infections and Staphylococcus aureus (S. aureus) is the most common causative pathogen in chronic bone infections (osteomyelitis). Treatment of these chronic bone infections often involves combinations of antibiotics given systemically and locally to the affected site via a biomaterial spacer. The gold standard biomaterial for local antibiotic delivery against osteomyelitis, poly(methyl methacrylate) (PMMA) bone cement, bears many limitations. Such shortcomings include limited antibiotic release, incompatibility with many antimicrobial agents, and the need for follow-up surgeries to remove the non-biodegradable cement before surgical reconstruction of the lost bone. Therefore, extensive research pursuits are targeting alternative, biodegradable materials to replace PMMA in osteomyelitis applications. Herein, we provide an overview of the primary clinical treatment strategies and emerging biodegradable materials that may be employed for management of implant-related osteomyelitis. We performed a systematic review of experimental biomaterials systems that have been evaluated for treating established S. aureus osteomyelitis in an animal model. Many experimental biomaterials were not decisively more efficacious for infection management than PMMA when delivering the same antibiotic. However, alternative biomaterials have reduced the number of follow-up surgeries, enhanced the antimicrobial efficacy by delivering agents that are incompatible with PMMA, and regenerated bone in an infected defect. Understanding the advantages, limitations, and potential for clinical translation of each biomaterial, along with the conditions under which it was evaluated (e.g. animal model), is critical for surgeons and researchers to navigate the plethora of options for local antibiotic delivery.

  5. Magnetic forces and magnetized biomaterials provide dynamic flux information during bone regeneration. (United States)

    Russo, Alessandro; Bianchi, Michele; Sartori, Maria; Parrilli, Annapaola; Panseri, Silvia; Ortolani, Alessandro; Sandri, Monica; Boi, Marco; Salter, Donald M; Maltarello, Maria Cristina; Giavaresi, Gianluca; Fini, Milena; Dediu, Valentin; Tampieri, Anna; Marcacci, Maurilio


    The fascinating prospect to direct tissue regeneration by magnetic activation has been recently explored. In this study we investigate the possibility to boost bone regeneration in an experimental defect in rabbit femoral condyle by combining static magnetic fields and magnetic biomaterials. NdFeB permanent magnets are implanted close to biomimetic collagen/hydroxyapatite resorbable scaffolds magnetized according to two different protocols . Permanent magnet only or non-magnetic scaffolds are used as controls. Bone tissue regeneration is evaluated at 12 weeks from surgery from a histological, histomorphometric and biomechanical point of view. The reorganization of the magnetized collagen fibers under the effect of the static magnetic field generated by the permanent magnet produces a highly-peculiar bone pattern, with highly-interconnected trabeculae orthogonally oriented with respect to the magnetic field lines. In contrast, only partial defect healing is achieved within the control groups. We ascribe the peculiar bone regeneration to the transfer of micro-environmental information, mediated by collagen fibrils magnetized by magnetic nanoparticles, under the effect of the static magnetic field. These results open new perspectives on the possibility to improve implant fixation and control the morphology and maturity of regenerated bone providing "in site" forces by synergically combining static magnetic fields and biomaterials.

  6. Development of Nano-biomaterials for Bone Repair

    Institute of Scientific and Technical Information of China (English)


    A new kind of nano-biomaterials of nano apatite ( NA ) and polyamide8063 ( PA ) composite was prepared by direct using NA slurry. The experimental results showed that the NA content in the composite was similar to that of natural bone. Interface chemical bonding was formed between NA and PA. The NA keeps the original morphological structure with a crystal size of 10- 30 nm in width by 50- 90 nm in length with a ratio of~ 2.5 and distributed uniformly in the polymer. The synthetic nano-biomaterials could be one of the best bioactive materials for load-bearing bone repair or substitution materials.


    Shirane, Henrique Yassuhiro; Oda, Diogo Yochizumi; Pinheiro, Thiago Cerizza; Cunha, Marcelo Rodrigues da


    To evaluate the importance of collagen and hydroxyapatite in the regeneration of fractures experimentally induced in the fibulas of rats. Method: 15 rats were used. These were subjected to surgery to remove a fragment from the fibula. This site then received a graft consisting of a silicone tubes filled with hydroxyapatite and collagen. Results: Little bone neoformation occurred inside the tubes filled with the biomaterials. There was more neoformation in the tubes with collagen. Conclusion: The biomaterials used demonstrated biocompatibility and osteoconductive capacity that was capable of stimulating osteogenesis, even in bones with secondary mechanical and morphological functions such as the fibula of rats. PMID:27047813

  8. Sustainable polysaccharide-based biomaterial recovered from waste aerobic granular sludge as a surface coating material

    NARCIS (Netherlands)

    Lin, Y. M.; Nierop, K.G.J.; Girbal-Neuhauser, E.; Adriaanse, M.; van Loosdrecht, M. C M


    To evaluate the possibility of utilizing polysaccharide-based biomaterial recovered from aerobic granular sludge as a coating material, the morphology, molecular weight distribution and chemical composition of the recovered biomaterial were investigated by atomic force microscopy, size exclusion chr

  9. Involvement of extracellular signal-regulated kinase (ERK1/2)-p53-p21 axis in mediating neural stem/progenitor cell cycle arrest in co-morbid HIV-drug abuse exposure. (United States)

    Malik, Shaily; Saha, Rinki; Seth, Pankaj


    Neurological complications in opioid abusing Human Immunodeficiency Virus-1 (HIV-1) patients suggest enhanced neurodegeneration as compared to non-drug abusing HIV-1 infected population. Neural precursor cells (NPCs), the multipotent cells of the mammalian brain, are susceptible to HIV-1 infection and as opiates also perturb their growth kinetics, detailed mechanistic studies for their co-morbid exposure are highly warranted. Using a well characterized in vitro model of human fetal brain-derived neural precursor cells, we investigated alterations in NPC properties at both acute and chronic durations. Chronic morphine and Tat treatment attenuated proliferation in NPCs, with cells stalled at G1-phase of the cell cycle. Furthermore HIV-Tat and morphine exposure increased activation of extracellular signal-regulated kinase-1/2 (ERK1/2), enhanced levels of p53 and p21, and decreased cyclin D1 and Akt levels in NPCs. Regulated by ERK1/2 and p53, p21 was found to be indispensible for Tat and morphine mediated cell cycle arrest. Our study elaborates on the cellular and molecular machinery in NPCs and provides significant mechanistic details into HIV-drug abuse co-morbidity that may have far reaching clinical consequences both in pediatric as well as adult neuroAIDS.

  10. 口服补液盐治疗儿童神经介导性晕厥研究进展%The research progress of oral rehydration salts treating neurally mediated syncope in children

    Institute of Scientific and Technical Information of China (English)



    Neurally mediated syncope (NMS) is the most common children unexplained syncope.Oral rehydration salts is the basis for the treatment of NMS.Oral rehydration salts can increase the extracellular fluid and blood volume,change the redistribution of blood,avoid the emptying effect caused by inadequate left ventricular filling volume when position changes suddenly,prevent increased vagus nerve activity induced syncope,can obviously increase the NMS children's ability of orthostatic intolerance.Increase water salt intake can be incorporated into the behavior training of the NMS children's daily life,and it can reduce the occurrence rate of NMS children,and improve the quality of life.%神经介导性晕厥(neurally mediated syncope,NMS)是儿童最常见的不明原因晕厥,口服补液盐是治疗NMS的基础用药,可增加细胞外液和血容量,改变血液的重新分布,避免突然体位变化时左室充盈量不足导致的排空效应,防止迷走神经活性增强诱发晕厥发作,能明显提高NMS儿童的直立不耐受能力.增加水盐摄入纳入NMS儿童日常生活中的行为习惯培养,可减少儿童NMS的出现率,提高其生活质量.

  11. The Effect of Biomaterials Used for Tissue Regeneration Purposes on Polarization of Macrophages

    NARCIS (Netherlands)

    G.S.A. Boersema (Geesien); N. Grotenhuis; Y. Bayon; J.F. Lange (Johan F.); Y.M. Bastiaansen-Jenniskens (Yvonne)


    textabstractActivation of macrophages is critical in the acute phase of wound healing after implantation of surgical biomaterials. To understand the response of macrophages, they are often cultured in vitro on biomaterials. Since a wide range of biomaterials is currently used in the clinics, we unde

  12. Preventing Vision Loss from Blast Injuries with Regenerative Biomaterial (United States)


    The material then hydrates and swells into a gel - like state, which then uniformly coats the surface and begins to dissolve with time. The bulk of the...mori silk fibroin solutions studied by 1 H NMR and rheology , Biomaterials 29, 4268–4274 (2008). 16. B. D. Lawrence, Z. Pan, M. D. Weber, D. L

  13. Detection of biomaterial-associated infections in orthopaedic joint implants

    NARCIS (Netherlands)

    Neut, D; van Horn, [No Value; van Kooten, TG; van der Mei, HC; Busscher, HJ


    Biomaterial-associated infection of orthopaedic joint replacements is the second most common cause of implant failure. Yet, the microbiologic detection rate of infection is relatively low, probably because routine hospital cultures are made only of swabs or small pieces of excised tissue and not of

  14. Surface Engineered Polymeric Biomaterials with Improved Biocontact Properties

    Directory of Open Access Journals (Sweden)

    Todorka G. Vladkova


    Full Text Available We present many examples of surface engineered polymeric biomaterials with nanosize modified layers, controlled protein adsorption, and cellular interactions potentially applicable for tissue and/or blood contacting devices, scaffolds for cell culture and tissue engineering, biosensors, biological microchips as well as approaches to their preparation.

  15. Standardization of incubation conditions for hemolysis testing of biomaterials

    NARCIS (Netherlands)

    Henkelman, Sandra; Rakhorst, Gerhard; Blanton, John; van Oeveren, Willem


    Hemolysis testing is the most common method to determine the hemocompatibility properties of biomaterials. There is however no consensus on the procedures of hemolysis testing due to insufficient comparative studies on the quality of the red blood cells used and the experimental conditions of testin

  16. Surface modification of polyester biomaterials for tissue engineering. (United States)

    Jiao, Yan-Peng; Cui, Fu-Zhai


    Surfaces play an important role in a biological system for most biological reactions occurring at surfaces and interfaces. The development of biomaterials for tissue engineering is to create perfect surfaces which can provoke specific cellular responses and direct new tissue regeneration. The improvement in biocompatibility of biomaterials for tissue engineering by directed surface modification is an important contribution to biomaterials development. Among many biomaterials used for tissue engineering, polyesters have been well documented for their excellent biodegradability, biocompatibility and nontoxicity. However, poor hydrophilicity and the lack of natural recognition sites on the surface of polyesters have greatly limited their further application in the tissue engineering field. Therefore, how to introduce functional groups or molecules to polyester surfaces, which ideally adjust cell/tissue biological functions, becomes more and more important. In this review, recent advances in polyester surface modification and their applications are reviewed. The development of new technologies or methods used to modify polyester surfaces for developing their biocompatibility is introduced. The results of polyester surface modifications by surface morphological modification, surface chemical group/charge modification, surface biomacromolecule modification and so on are reported in detail. Modified surface properties of polyesters directly related to in vitro/vivo biological performances are presented as well, such as protein adsorption, cell attachment and growth and tissue response. Lastly, the prospect of polyester surface modification is discussed, especially the current conception of biomimetic and molecular recognition.

  17. MO-FG-BRA-04: Leveraging the Abscopal Effect Via New Design Radiotherapy Biomaterials Loaded with Immune Checkpoint Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Y; Cifter, G; Altundal, Y; Moreau, M; Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Sinha, N [Wentworth Institute of Technology, Boston, MA (United States); Makrigiorgos, G [Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Ngwa, W [Univ Massachusetts Lowell, Lowell, MA (United States); Dana Farber Cancer Institute, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)


    Purpose: Studies show that stereotactic body radiation therapy (SBRT) of a primary tumor in combination with immune checkpoint inhibitors (ICI) could Result in an immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However toxicities due to repeated systematic administration of ICI have been shown to be a major obstacle in clinical trials. Towards overcoming these toxicity limitations, we investigate a potential new approach whereby the ICI are administered via sustained in-situ release from radiotherapy (RT) biomaterials (e.g. fiducials) coated with a polymer containing the ICI. Methods: New design RT biomaterials were prepared by coating commercially available spacers/fiducials with a biocompatible polymer (PLGA) film containing fluorescent nanoparticles of size needed to load the ICI. The release of the nanoparticles was investigated in-vitro. Meanwhile, an experimentally determined in- vivo nanoparticle diffusion coefficient was employed in analytic calculations based on Fick’s second law to estimate the time for achieving the concentrations of ICI in the tumor draining lymph node (TDLN) that are needed to engender the abscopal effect during SBRT. The ICI investigated here was anti-CTLA-4 antibody (ipilimumab) at approved FDA concentrations. Results: Our in -vitro study results showed that RT biomaterials could be designed to achieve burst release of nanoparticles within one day. Meanwhile, our calculations indicate that for a 2 to 4 cm tumor it would take 4–22 days, respectively, following burst release, for the required concentration of ICI nanoparticles to accumulate in the TDLN during SBRT. Conclusion: Current investigations combining RT and immunotherapy involve repeated intravenous administration of ICI leading to significant systemic toxicities. Our preliminary results highlight a potential new approach for sustained in-situ release of the ICI from new design RT biomaterials. These results

  18. NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas. (United States)

    Osborne, Jihan K; Guerra, Marcy L; Gonzales, Joshua X; McMillan, Elizabeth A; Minna, John D; Cobb, Melanie H


    Cigarette smoking is a major risk factor for acquisition of small cell lung cancer (SCLC). A role has been demonstrated for the basic helix-loop-helix transcription factor NeuroD1 in the pathogenesis of neural and neuroendocrine lung cancer, including SCLC. In the present study we investigate the possible function of NeuroD1 in established tumors, as well as actions early on in pathogenesis, in response to nicotine. We demonstrate that nicotine up-regulates NeuroD1 in immortalized normal bronchial epithelial cells and a subset of undifferentiated carcinomas. Increased expression of NeuroD1 subsequently leads to regulation of expression and function of the nicotinic acetylcholine receptor subunit cluster of α3, α5, and β4. In addition, we find that coordinated expression of these subunits by NeuroD1 leads to enhanced nicotine-induced migration and invasion, likely through changes in intracellular calcium. These findings suggest that aspects of the pathogenesis of neural and neuroendocrine lung cancers may be affected by a nicotine- and NeuroD1-induced positive feedback loop.

  19. Neural mechanisms mediating positive and negative treatment expectations in visceral pain: a functional magnetic resonance imaging study on placebo and nocebo effects in healthy volunteers. (United States)

    Schmid, Julia; Theysohn, Nina; Gaß, Florian; Benson, Sven; Gramsch, Carolin; Forsting, Michael; Gizewski, Elke R; Elsenbruch, Sigrid


    To elucidate placebo and nocebo effects in visceral pain, we conducted a functional magnetic resonance imaging (fMRI) study to analyze effects of positive and negative treatment expectations in a rectal pain model. In 36 healthy volunteers, painful rectal distensions were delivered after intravenous application of an inert substance combined with either positive instructions of pain relief (placebo group) or negative instructions of pain increase (nocebo group), each compared to neutral instructions. Neural activation during cued-pain anticipation and pain was analyzed along with expected and perceived pain intensity. Expected and perceived pain intensity were significantly increased in the nocebo group and significantly decreased in the placebo group. In the placebo group, positive expectations significantly reduced activation of the somatosensory cortex during anticipation and of the insula, somatosensory cortex, and amygdala during pain delivery when compared to neutral expectations. Within the nocebo group, negative expectations led to significantly increased insula activation during painful stimulation. Direct group contrasts during expectation modulation revealed significantly increased distension-induced activation within the somatosensory cortex in the nocebo group. In conclusion, the experience and neural processing of visceral pain can be increased or decreased by drug-specific expectations. This first brain imaging study on nocebo effects in visceral pain has implications for the pathophysiology and treatment of patients with chronic abdominal complaints such as irritable bowel syndrome.

  20. 3' UTR-dependent, miR-92-mediated restriction of Tis21 expression maintains asymmetric neural stem cell division to ensure proper neocortex size. (United States)

    Fei, Ji-Feng; Haffner, Christiane; Huttner, Wieland B


    Mammalian neocortex size primarily reflects the number and mode of divisions of neural stem and progenitor cells. Cortical stem cells (apical progenitors) switching from symmetric divisions, which expand their population, to asymmetric divisions, which generate downstream neuronal progenitors (basal progenitors), start expressing Tis21, a so-called antiproliferative/prodifferentiative gene. Tis21 encodes a small (17.5 kDa), functionally poorly characterized protein and a relatively large (2 kb), highly conserved 3' UTR. Here, we show that mice lacking the Tis21 3' UTR develop a microcephalic neocortex with fewer neurons, notably in the upper layers. This reflects a progressive decrease in basal progenitors, which in turn is due to a fraction of apical progenitors prematurely switching from asymmetric self-renewing to symmetric self-consuming divisions. This switch is caused by the markedly increased Tis21 protein level resulting from lack of microRNA-, notably miR-92-, dependent restriction of Tis21 expression. Our data show that a premature onset of consumptive neural stem cell divisions can lead to microcephaly.

  1. Transcription activator-like effector nuclease (TALEN-mediated CLYBL targeting enables enhanced transgene expression and one-step generation of dual reporter human induced pluripotent stem cell (iPSC and neural stem cell (NSC lines.

    Directory of Open Access Journals (Sweden)

    Trevor Cerbini

    Full Text Available Targeted genome engineering to robustly express transgenes is an essential methodology for stem cell-based research and therapy. Although designer nucleases have been used to drastically enhance gene editing efficiency, targeted addition and stable expression of transgenes to date is limited at single gene/locus and mostly PPP1R12C/AAVS1 in human stem cells. Here we constructed transcription activator-like effector nucleases (TALENs targeting the safe-harbor like gene CLYBL to mediate reporter gene integration at 38%-58% efficiency, and used both AAVS1-TALENs and CLYBL-TALENs to simultaneously knock-in multiple reporter genes at dual safe-harbor loci in human induced pluripotent stem cells (iPSCs and neural stem cells (NSCs. The CLYBL-TALEN engineered cell lines maintained robust reporter expression during self-renewal and differentiation, and revealed that CLYBL targeting resulted in stronger transgene expression and less perturbation on local gene expression than PPP1R12C/AAVS1. TALEN-mediated CLYBL engineering provides improved transgene expression and options for multiple genetic modification in human stem cells.

  2. Transcription activator-like effector nuclease (TALEN)-mediated CLYBL targeting enables enhanced transgene expression and one-step generation of dual reporter human induced pluripotent stem cell (iPSC) and neural stem cell (NSC) lines. (United States)

    Cerbini, Trevor; Funahashi, Ray; Luo, Yongquan; Liu, Chengyu; Park, Kyeyoon; Rao, Mahendra; Malik, Nasir; Zou, Jizhong


    Targeted genome engineering to robustly express transgenes is an essential methodology for stem cell-based research and therapy. Although designer nucleases have been used to drastically enhance gene editing efficiency, targeted addition and stable expression of transgenes to date is limited at single gene/locus and mostly PPP1R12C/AAVS1 in human stem cells. Here we constructed transcription activator-like effector nucleases (TALENs) targeting the safe-harbor like gene CLYBL to mediate reporter gene integration at 38%-58% efficiency, and used both AAVS1-TALENs and CLYBL-TALENs to simultaneously knock-in multiple reporter genes at dual safe-harbor loci in human induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs). The CLYBL-TALEN engineered cell lines maintained robust reporter expression during self-renewal and differentiation, and revealed that CLYBL targeting resulted in stronger transgene expression and less perturbation on local gene expression than PPP1R12C/AAVS1. TALEN-mediated CLYBL engineering provides improved transgene expression and options for multiple genetic modification in human stem cells.

  3. NCAM-mimetic, FGL peptide, restores disrupted fibroblast growth factor receptor (FGFR) phosphorylation and FGFR mediated signaling in neural cell adhesion molecule (NCAM)-deficient mice

    DEFF Research Database (Denmark)

    Aonurm-Helm, Anu; Berezin, Vladimir; Bock, Elisabeth;


    Neural cell adhesion molecule (NCAM) is a membrane-bound glycoprotein expressed on the surface of neuronal and glial cells. Previous in vitro studies have demonstrated that NCAM promotes neuronal functions largely via three main interaction partners: the fibroblast growth factor receptor (FGFR...... compared the levels of phosphorylation of FGFR1, Src kinase Fyn, Raf1 kinase, MAP kinases, Akt kinase and calcium/calmodulin-dependent kinases II and IV (CaMKII and CaMKIV) in the hippocampus of NCAM knockout mice to their wild-type littermates. The data of our study show that mice constitutively deficient...... in all isoforms of NCAM have decreased basal phosphorylation levels of FGFR1 and CaMKII and CaMKIV. Furthermore, NCAM-mimetic, FGL peptide, is found to be able to restore FGFR1, CaMKII and CaMKIV phosphorylation levels and thereby mimic the interactions of NCAM at this receptor in NCAM deficient mice...

  4. STK25 protein mediates TrkA and CCM2 protein-dependent death in pediatric tumor cells of neural origin. (United States)

    Costa, Barbara; Kean, Michelle J; Ast, Volker; Knight, James D R; Mett, Alice; Levy, Zehava; Ceccarelli, Derek F; Badillo, Beatriz Gonzalez; Eils, Roland; König, Rainer; Gingras, Anne-Claude; Fainzilber, Mike


    The TrkA receptor tyrosine kinase induces death in medulloblastoma cells via an interaction with the cerebral cavernous malformation 2 (CCM2) protein. We used affinity proteomics to identify the germinal center kinase class III (GCKIII) kinases STK24 and STK25 as novel CCM2 interactors. Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2. CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling. Finally, STK25 expression in tumors is correlated with positive prognosis in neuroblastoma patients. These findings delineate a death-signaling pathway downstream of neurotrophic receptor tyrosine kinases that may provide targets for therapeutic intervention in pediatric tumors of neural origin.

  5. Preparation of novel functional Mg/O/PCL/ZnO composite biomaterials and their corrosion resistance

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Zhongxian; Tan, Cui; Xu, Lan; Yang, Na; Li, Qing, E-mail:


    Highlights: • Novel functional Mg/O/PCL/ZnO composite biomaterials were prepared. • The biomaterials were prepared by anodization treatment and dip-coating technique. • The composite biomaterials were smooth and with low porosity. • The prepared biomaterials have good corrosion resistance in SBF. • The composite biomaterials can release zinc ion to promote bone formation. - Abstract: In this study, novel and functional Mg/O/PCL/ZnO (magnesium/anodic film/poly(ε-caprolactone)/zinc oxide) composite biomaterials for enhancing the bioactivity and biocompatibility of the implant was prepared by using anodization treatment and dip-coating technique. The surface morphology, microstructure, adhesion strength and corrosion resistance of the composite biomaterials were investigated using scanning electron microscopy (SEM), adhesion measurements, electrochemical tests and immersion tests respectively. In addition, the biocompatible properties of Mg (magnesium), Mg/PCL (magnesium/poly(ε-caprolactone)) and Mg/O/PCL (magnesium/anodic film/poly(ε-caprolactone)) samples were also investigated. The results show that the Mg/O/PCL/ZnO composite biomaterials were with low porosity and with the ZnO powders dispersed in PCL uniformly. The adhesion tests suggested that Mg/O/PCL/ZnO composite biomaterials had better adhesion strength than that of Mg/PCL composite biomaterials obviously. Besides, an in vitro test for corrosion demonstrated that the Mg/O/PCL/ZnO composite biomaterials had good corrosion resistance and zinc ion was released obviously in SBF.

  6. Collagen-Based Biomaterials for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    François Berthod


    Full Text Available Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.

  7. Global gene expression analysis for evaluation and design of biomaterials

    Directory of Open Access Journals (Sweden)

    Nobutaka Hanagata, Taro Takemura and Takashi Minowa


    Full Text Available Comprehensive gene expression analysis using DNA microarrays has become a widespread technique in molecular biological research. In the biomaterials field, it is used to evaluate the biocompatibility or cellular toxicity of metals, polymers and ceramics. Studies in this field have extracted differentially expressed genes in the context of differences in cellular responses among multiple materials. Based on these genes, the effects of materials on cells at the molecular level have been examined. Expression data ranging from several to tens of thousands of genes can be obtained from DNA microarrays. For this reason, several tens or hundreds of differentially expressed genes are often present in different materials. In this review, we outline the principles of DNA microarrays, and provide an introduction to methods of extracting information which is useful for evaluating and designing biomaterials from comprehensive gene expression data.


    Energy Technology Data Exchange (ETDEWEB)

    Brigmon, R.; Berry, T.; Narayan, R.


    Biotechnology is the application of biological techniques to develop new tools and products for medicine and industry. Due to various properties including chemical stability, biocompatibility, and specific activity, e.g. antimicrobial properties, many new and novel materials are being investigated for use in biosensing, drug delivery, hemodialysis, and other medical applications. Many of these materials are less than 100 nanometers in size. Nanotechnology is the engineering discipline encompassing designing, producing, testing, and using structures and devices less than 100 nanometers. One of the challenges associated with biomaterials is microbial contamination that can lead to infections. In recent work we have examined the functionalization of nanoporous biomaterials and antimicrobial activities of nanocrystalline diamond materials. In vitro testing has revealed little antimicrobial activity against Pseudomonas fluorescens bacteria and associated biofilm formation that enhances recalcitrance to antimicrobial agents including disinfectants and antibiotics. Laser scanning confocal microscopy studies further demonstrated properties and characteristics of the material with regard to biofilm formation.

  9. Nuclear corrosion monitoring- : NCM-applied to biomaterials. (United States)

    Brune, D


    Nuclear corrosion technique has been developed for the assay of various heavy metals released through corrosion and abrasion into electrolytes from various biomaterials like amalgams, chromium- cobalt and gold alloys, steel, and titanium. Application of the technique in measurement of selective release rates under static or dynamic conditions, i.e., during cyclic loading, is discussed. The elements chromium, cobalt, copper, gold, iron, mercury, molybdenum, silver, titanium, and zinc have been quantitatively assessed. In vivo corrosion measurements are further included. By combining the present nuclear tracer technique with ESCA technique, knowledge about reaction mechanisms occurring at the interface solid/liquid is obtained. Exposure of humans to various heavy metals from biomaterials, e.g., dental materials, can be estimated using the NCM technique. The technique also has a potential for selective release measurements of several nuclides possessing suitable radioanalytical properties from other types of alloys immersed in various liquid environments.

  10. In Vitro Endothelialization Test of Biomaterials Using Immortalized Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Ken Kono

    Full Text Available Functionalizing biomaterials with peptides or polymers that enhance recruitment of endothelial cells (ECs can reduce blood coagulation and thrombosis. To assess endothelialization of materials in vitro, primary ECs are generally used, although the characteristics of these cells vary among the donors and change with time in culture. Recently, primary cell lines immortalized by transduction of simian vacuolating virus 40 large T antigen or human telomerase reverse transcriptase have been developed. To determine whether immortalized ECs can substitute for primary ECs in material testing, we investigated endothelialization on biocompatible polymers using three lots of primary human umbilical vein endothelial cells (HUVEC and immortalized microvascular ECs, TIME-GFP. Attachment to and growth on polymer surfaces were comparable between cell types, but results were more consistent with TIME-GFP. Our findings indicate that TIME-GFP is more suitable for in vitro endothelialization testing of biomaterials.


    Directory of Open Access Journals (Sweden)

    Lois Larbie


    Full Text Available In this study we investigate the cytotoxicity of de-starched cassava fibre granules and fine powder using human peripheral blood mononuclear cells (PBMC and examine changes in the composition of Simulated Body Fluid (SBF resulting from immersion of cassava fibre samples. The purpose of the study was to characterise cassavafibre for possible biomaterial applications. Preliminary results indicate insignificant cytotoxic effects on PBMCs with cassava sample concentrations of 0.1g/ml, 0.025g/ml and 0.00625g/ml. Additionally there was little or no significant change in Na, K, Mg, Cl, Ca, Mn, and Cu concentrations upon immersion in SBF as observed over a one week period at a temperature of 37°C. These initial results suggest cassava fibre may be considered for biomaterial applications following more extensive characterisation.

  12. Nanoindentation Studies of TNZ and Ti2448 Biomaterials After Magnetoelectropolishing

    Directory of Open Access Journals (Sweden)

    Hryniewicz T.


    Full Text Available This work presents the nanoindentation results of two newly developed titanium alloy biomaterials, TNZ and Ti2448, after different surface treatments. The investigations were performed on the samples, AR – as received, MP – after abrasive polishing, EP – after a standard electropolshing, and MEP – after magnetoelectropolishing. The electropolishing processes, both EP and MEP, were conducted in the same proprietary electrolyte based on concentrated sulfuric acid. The mechanical properties of the titanium alloys biomaterials demonstrated an evident dependence on the surface treatment method, with MEP samples revealing extremely different behaviour and mechanical properties. Such a different mechanical behaviour may mean completely different composition and thickness of the surface film formed on the studied samples after MEP

  13. Towards practical soft X-ray spectromicroscopy of biomaterials. (United States)

    Hitchcock, A P; Morin, C; Heng, Y M; Cornelius, R M; Brash, J L


    Scanning transmission X-ray microscopy (STXM) is being developed as a new tool to study the surface chemical morphology and biointeractions of candidate biomaterials with emphasis on blood compatible polymers. STXM is a synchrotron based technique which provides quantitative chemical mapping at a spatial resolution of 50 nm. Chemical speciation is provided by the near edge X-ray absorption spectral (NEXAFS) signal. We show that STXM can detect proteins on soft X-ray transparent polymer thin films with monolayer sensitivity. Of great significance is the fact that measurements can be made in situ, i.e. in the presence of an overlayer of the protein solution. The strengths, limitations and future potential of STXM for studies of biomaterials are discussed.

  14. Application of Biomaterials in Cardiac Repair and Regeneration

    Directory of Open Access Journals (Sweden)

    Zhi Cui


    Full Text Available Cardiovascular disease is a leading cause of death throughout the world. The demand for new therapeutic interventions is increasing. Although pharmacological and surgical interventions dramatically improve the quality of life of cardiovascular disease patients, cheaper and less invasive approaches are always preferable. Biomaterials, both natural and synthetic, exhibit great potential in cardiac repair and regeneration, either as a carrier for drug delivery or as an extracellular matrix substitute scaffold. In this review, we discuss the current treatment options for several cardiovascular diseases, as well as types of biomaterials that have been investigated as potential therapeutic interventions for said diseases. We especially highlight investigations into the possible use of conductive polymers for correcting ischemic heart disease-induced conduction abnormalities, and the generation of biological pacemakers to improve the conduction pathway in heart block.

  15. Up-regulation of Siah1 by ethanol triggers apoptosis in neural crest cells through p38 MAPK-mediated activation of p53 signaling pathway. (United States)

    Yuan, Fuqiang; Chen, Xiaopan; Liu, Jie; Feng, Wenke; Wu, Xiaoyang; Chen, Shao-Yu


    Seven in absentia homolog 1 (Siah1) is one of the E3 ubiquitin ligases and plays a key role in regulating target protein degradation. This study was designed to test the hypothesis that Siah1 mediates ethanol-induced apoptosis in NCCs through p38 MAPK-mediated activation of the p53 signaling pathway. We found that exposure of NCCs to ethanol resulted in the increases in the total protein levels of p53 and the phosphorylation of p53 at serine 15. Ethanol exposure also resulted in a significant increase in the phosphorylation of p38 MAPK. Knock-down of Siah1 dramatically reduced the ethanol-induced increase in the phosphorylation of p38 MAPK. Knock-down of Siah1 by siRNA or down-regulation of p38 MAPK by either siRNA or inhibitor significantly diminished ethanol-induced accumulations of p53 and the phosphorylation of p53. In addition, ethanol exposure resulted in a significant increase in the expression of p53 downstream targets and apoptosis in NCCs, which can be significantly diminished by down-regulation of Siah1 with siRNA. Knock-down of p38 MAPK by siRNA also dramatically reduced the ethanol-induced apoptosis. These results demonstrate that Siah1 plays a crucial role in ethanol-induced apoptosis in NCCs, and that the up-regulation of Siah1 by ethanol can trigger apoptosis through p38 MAPK-mediated activation of the p53 signaling pathway.

  16. Complement inhibition in biomaterial- and biosurface-induced thromboinflammation


    Ekdahl, Kristina N.; Huang, Shan; Nilsson, Bo; Teramura, Yuji


    Therapeutic medicine today includes a vast number of procedures involving the use of biomaterials, transplantation of therapeutic cells or cell clusters, as well as of solid organs. These treatment modalities are obviously of great benefit to the patient, but also present a great challenge to the innate immune system, since they involve direct exposure of non-biological materials, cells of non-hematological origin as well as endothelial cells, damaged by ischemia-perfusion in solid organs to ...

  17. Preventing Vision Loss from Blast Injuries with Regenerative Biomaterial (United States)


    biomaterial derived from the silk protein fibroin from the Bombyx mori silkworm . This will be the first ophthalmic product that utilizes regenerative silk...the Bombyx mori silkworm cocoon is not toxic and non-immunogenic when placed within the body (1). It is also known that silk fibroin possesses anti...which dissolve silkworm cocoons into an aqueous protein solution (10). The variability in producing silk solution has been a significant challenge for

  18. All-biomaterial laser using vitamin and biopolymers. (United States)

    Nizamoglu, Sedat; Gather, Malte C; Yun, Seok Hyun


    Lasers based on biomaterials known as Generally-Recognized-As-Safe (GRAS) substances approved by the U.S. Food and Drug Administration (FDA) are demonstrated. Vitamin B2-doped microdroplet lasers are generated and trapped on a super-hydrophobic poly-L-lactic acid substrate. The spheres support whispering gallery mode lasing at optical pump energies as low as 15 nJ per pulse (≈1 kW/mm2).

  19. Chitosan improves the biological performance of soy-based biomaterials


    Santos, T. C.; MARQUES, A.P.; SILVA, S. S.; Oliveira, Joaquim M.; Mano, J. F.; Castro, António G.; van Griensven, Martijn; Reis, R. L.


    Soybean protein has been proposed for distinct applications within nutritional, pharmaceutical, and cosmetic industries among others. More recently, soy-based biomaterials have also demonstrated promising properties for biomedical applications.However, althoughmany reports within other fields exist, the inflammatory/immunogenic potential of those materials is still poorly understood and therefore can hardly be controlled. On the contrary, chitosan (Cht) has been well explored in t...

  20. Clay: New opportunities for tissue regeneration and biomaterial design


    Dawson, Jonathan I.; Oreffo, Richard O.C.


    Seminal recent studies that have shed new light on the remarkable properties of clay interactions suggest unexplored opportunities for biomaterial design and regenerative medicine. Here, recent conceptual and technological developments in the science of clay interactions with biomolecules, polymers, and cells are examined, focusing on the implications for tissue engineering and regenerative strategies. Pioneering studies demonstrating the utility of clay for drug-delivery and scaffold design ...

  1. Musculoskeletal Regenerative Engineering: Biomaterials, Structures, and Small Molecules


    Roshan James; Laurencin, Cato T.


    Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to re-engineer/guide stem cells to yield the desired organ cells and tissues. Tissue engineering strategies were ideally suited to repair damaged tissues; however, the substitution and regeneration of large tissue vo...

  2. Foxg1-Cre Mediated Lrp2 Inactivation in the Developing Mouse Neural Retina, Ciliary and Retinal Pigment Epithelia Models Congenital High Myopia (United States)

    Obry, Antoine; Santin, Mathieu D.; Ben-Yacoub, Sirine; Pâques, Michel; Amsellem-Levera, Sabine; Bribian, Ana; Simonutti, Manuel; Augustin, Sébastien; Debeir, Thomas; Sahel, José Alain; Christ, Annabel; de Castro, Fernando; Lehéricy, Stéphane; Cosette, Pascal; Kozyraki, Renata


    Myopia is a common ocular disorder generally due to increased axial length of the eye-globe. Its extreme form high myopia (HM) is a multifactorial disease leading to retinal and scleral damage, visual impairment or loss and is an important health issue. Mutations in the endocytic receptor LRP2 gene result in Donnai-Barrow (DBS) and Stickler syndromes, both characterized by HM. To clearly establish the link between Lrp2 and congenital HM we inactivated Lrp2 in the mouse forebrain including the neural retina and the retinal and ciliary pigment epithelia. High resolution in vivo MRI imaging and ophthalmological analyses showed that the adult Lrp2-deficient eyes were 40% longer than the control ones mainly due to an excessive elongation of the vitreal chamber. They had an apparently normal intraocular pressure and developed chorioretinal atrophy and posterior scleral staphyloma features reminiscent of human myopic retinopathy. Immunomorphological and ultrastructural analyses showed that increased eye lengthening was first observed by post-natal day 5 (P5) and that it was accompanied by a rapid decrease of the bipolar, photoreceptor and retinal ganglion cells, and eventually the optic nerve axons. It was followed by scleral thinning and collagen fiber disorganization, essentially in the posterior pole. We conclude that the function of LRP2 in the ocular tissues is necessary for normal eye growth and that the Lrp2-deficient eyes provide a unique tool to further study human HM. PMID:26107939

  3. CRISPR-Mediated Genomic Deletion of Sox2 in the Axolotl Shows a Requirement in Spinal Cord Neural Stem Cell Amplification during Tail Regeneration

    Directory of Open Access Journals (Sweden)

    Ji-Feng Fei


    Full Text Available The salamander is the only tetrapod that functionally regenerates all cell types of the limb and spinal cord (SC and thus represents an important regeneration model, but the lack of gene-knockout technology has limited molecular analysis. We compared transcriptional activator-like effector nucleases (TALENs and clustered regularly interspaced short palindromic repeats (CRISPRs in the knockout of three loci in the axolotl and find that CRISPRs show highly penetrant knockout with less toxic effects compared to TALENs. Deletion of Sox2 in up to 100% of cells yielded viable F0 larvae with normal SC organization and ependymoglial cell marker expression such as GFAP and ZO-1. However, upon tail amputation, neural stem cell proliferation was inhibited, resulting in spinal-cord-specific regeneration failure. In contrast, the mesodermal blastema formed normally. Sox3 expression during development, but not regeneration, most likely allowed embryonic survival and the regeneration-specific phenotype. This analysis represents the first tissue-specific regeneration phenotype from the genomic deletion of a gene in the axolotl.

  4. ALK5-mediated transforming growth factor β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions. (United States)

    Han, Arum; Zhao, Hu; Li, Jingyuan; Pelikan, Richard; Chai, Yang


    The development of the craniofacial muscles requires reciprocal interactions with surrounding craniofacial tissues that originate from cranial neural crest cells (CNCCs). However, the molecular mechanism involved in the tissue-tissue interactions between CNCCs and muscle progenitors during craniofacial muscle development is largely unknown. In the current study, we address how CNCCs regulate the development of the tongue and other craniofacial muscles using Wnt1-Cre; Alk5(fl/fl) mice, in which loss of Alk5 in CNCCs results in severely disrupted muscle formation. We found that Bmp4 is responsible for reduced proliferation of the myogenic progenitor cells in Wnt1-Cre; Alk5(fl/fl) mice during early myogenesis. In addition, Fgf4 and Fgf6 ligands were reduced in Wnt1-Cre; Alk5(fl/fl) mice and are critical for differentiation of the myogenic cells. Addition of Bmp4 or Fgf ligands rescues the proliferation and differentiation defects in the craniofacial muscles of Alk5 mutant mice in vitro. Taken together, our results indicate that CNCCs play critical roles in controlling craniofacial myogenic proliferation and differentiation through tissue-tissue interactions.

  5. DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Sònia Najas


    Full Text Available Alterations in cerebral cortex connectivity lead to intellectual disability and in Down syndrome, this is associated with a deficit in cortical neurons that arises during prenatal development. However, the pathogenic mechanisms that cause this deficit have not yet been defined. Here we show that the human DYRK1A kinase on chromosome 21 tightly regulates the nuclear levels of Cyclin D1 in embryonic cortical stem (radial glia cells, and that a modest increase in DYRK1A protein in transgenic embryos lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages. Moreover, radial glial progenitors in the Ts65Dn mouse model of Down syndrome have less Cyclin D1, and Dyrk1a is the triplicated gene that causes both early cortical neurogenic defects and decreased nuclear Cyclin D1 levels in this model. These data provide insights into the mechanisms that couple cell cycle regulation and neuron production in cortical neural stem cells, emphasizing that the deleterious effect of DYRK1A triplication in the formation of the cerebral cortex begins at the onset of neurogenesis, which is relevant to the search for early therapeutic interventions in Down syndrome.

  6. CRISPR-mediated genomic deletion of Sox2 in the axolotl shows a requirement in spinal cord neural stem cell amplification during tail regeneration. (United States)

    Fei, Ji-Feng; Schuez, Maritta; Tazaki, Akira; Taniguchi, Yuka; Roensch, Kathleen; Tanaka, Elly M


    The salamander is the only tetrapod that functionally regenerates all cell types of the limb and spinal cord (SC) and thus represents an important regeneration model, but the lack of gene-knockout technology has limited molecular analysis. We compared transcriptional activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs) in the knockout of three loci in the axolotl and find that CRISPRs show highly penetrant knockout with less toxic effects compared to TALENs. Deletion of Sox2 in up to 100% of cells yielded viable F0 larvae with normal SC organization and ependymoglial cell marker expression such as GFAP and ZO-1. However, upon tail amputation, neural stem cell proliferation was inhibited, resulting in spinal-cord-specific regeneration failure. In contrast, the mesodermal blastema formed normally. Sox3 expression during development, but not regeneration, most likely allowed embryonic survival and the regeneration-specific phenotype. This analysis represents the first tissue-specific regeneration phenotype from the genomic deletion of a gene in the axolotl.

  7. DMPD: The interrelated role of fibronectin and interleukin-1 in biomaterial-modulatedmacrophage function. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16978691 The interrelated role of fibronectin and interleukin-1 in biomaterial-modu...latedmacrophage function. Schmidt DR, Kao WJ. Biomaterials. 2007 Jan;28(3):371-82. Epub 2006 Sep 15. (.png) ...(.svg) (.html) (.csml) Show The interrelated role of fibronectin and interleukin-1 in biomaterial-modulatedm...and interleukin-1 in biomaterial-modulatedmacrophage function. Authors Schmidt DR, Kao WJ. Publication Biomaterial...acrophage function. PubmedID 16978691 Title The interrelated role of fibronectin

  8. Biomaterials in Cardiovascular Research: Applications and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Saravana Kumar Jaganathan


    Full Text Available Cardiovascular biomaterials (CB dominate the category of biomaterials based on the demand and investments in this field. This review article classifies the CB into three major classes, namely, metals, polymers, and biological materials and collates the information about the CB. Blood compatibility is one of the major criteria which limit the use of biomaterials for cardiovascular application. Several key players are associated with blood compatibility and they are discussed in this paper. To enhance the compatibility of the CB, several surface modification strategies were in use currently. Some recent applications of surface modification technology on the materials for cardiovascular devices were also discussed for better understanding. Finally, the current trend of the CB, endothelization of the cardiac implants and utilization of induced human pluripotent stem cells (ihPSCs, is also presented in this review. The field of CB is growing constantly and many new investigators and researchers are developing interest in this domain. This review will serve as a one stop arrangement to quickly grasp the basic research in the field of CB.

  9. Silicon: the evolution of its use in biomaterials. (United States)

    Henstock, J R; Canham, L T; Anderson, S I


    In the 1970s, several studies revealed the requirement for silicon in bone development, while bioactive silicate glasses simultaneously pioneered the current era of bioactive materials. Considerable research has subsequently focused on the chemistry and biological function of silicon in bone, demonstrating that the element has at least two separate effects in the extracellular matrix: (i) interacting with glycosaminoglycans and proteoglycans during their synthesis, and (ii) forming ionic substitutions in the crystal lattice structure of hydroxyapatite. In addition, the dissolution products of bioactive glass (predominantly silicic acids) have significant effects on the molecular biology of osteoblasts in vitro, regulating the expression of several genes including key osteoblastic markers, cell cycle regulators and extracellular matrix proteins. Researchers have sought to capitalize on these effects and have generated a diverse array of biomaterials, which include bioactive glasses, silicon-substituted hydroxyapatites and pure, porosified silicon, but all these materials share similarities in the mechanisms that result in their bioactivity. This review discusses the current data obtained from original research in biochemistry and biomaterials science supporting the role of silicon in bone, comparing both the biological function of the element and analysing the evolution of silicon-containing biomaterials.

  10. Nanostructured Biomaterials for Tissue Engineered Bone Tissue Reconstruction

    Directory of Open Access Journals (Sweden)

    Bressan Eriberto


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

  11. Complex Particulate Biomaterials as Immunostimulant-Delivery Platforms (United States)

    Mamat, Uwe; Wilke, Kathleen; Villaverde, Antonio; Roher, Nerea


    The control of infectious diseases is a major current challenge in intensive aquaculture. Most commercial vaccines are based on live attenuated or inactivated pathogens that are usually combined with adjuvants, oil emulsions being as the most widely used for vaccination in aquaculture. Although effective, the use of these oil emulsions is plagued with important side effects. Thus, the development of alternative safer and cost-effective immunostimulants and adjuvants is highly desirable. Here we have explored the capacity of inclusion bodies produced in bacteria to immunostimulate and protect fish against bacterial infections. Bacterial inclusion bodies are highly stable, non-toxic protein-based biomaterials produced through fully scalable and low-cost bio-production processes. The present study shows that the composition and structured organization of inclusion body components (protein, lipopolysaccharide, peptidoglycan, DNA and RNA) make these protein biomaterials excellent immunomodulators able to generically protect fish against otherwise lethal bacterial challenges. The results obtained in this work provide evidence that their inherent nature makes bacterial inclusion bodies exceptionally attractive as immunostimulants and this opens the door to the future exploration of this biomaterial as an alternative adjuvant for vaccination purposes in veterinary. PMID:27716780

  12. Novel biomaterials: plasma-enabled nanostructures and functions (United States)

    Levchenko, Igor; Keidar, Michael; Cvelbar, Uroš; Mariotti, Davide; Mai-Prochnow, Anne; Fang, Jinghua; (Ken Ostrikov, Kostya


    Material processing techniques utilizing low-temperature plasmas as the main process tool feature many unique capabilities for the fabrication of various nanostructured materials. As compared with the neutral-gas based techniques and methods, the plasma-based approaches offer higher levels of energy and flux controllability, often leading to higher quality of the fabricated nanomaterials and sometimes to the synthesis of the hierarchical materials with interesting properties. Among others, nanoscale biomaterials attract significant attention due to their special properties towards the biological materials (proteins, enzymes), living cells and tissues. This review briefly examines various approaches based on the use of low-temperature plasma environments to fabricate nanoscale biomaterials exhibiting high biological activity, biological inertness for drug delivery system, and other features of the biomaterials make them highly attractive. In particular, we briefly discuss the plasma-assisted fabrication of gold and silicon nanoparticles for bio-applications; carbon nanoparticles for bioimaging and cancer therapy; carbon nanotube-based platforms for enzyme production and bacteria growth control, and other applications of low-temperature plasmas in the production of biologically-active materials.

  13. Scattering Anisotropy Measurements in Dental Tissues and Biomaterials (United States)

    Fernandez-Oliveras, A.; Rubiño, M.; Perez, M. M.


    Understanding the behaviour of light propagation in biological materials is essential for biomedical engineering and applications, and even more so when dealing with incoming biomaterials. Many methods for determining optical parameters from biological media assume that scattered light is isotropically distributed over all angles. However, an angular dependence of light scattering may exist and affect the optical behaviour of biological media. The present work seeks to experimentally analyze the scattering anisotropy in different dental tissues (enamel and dentine) and their potential substitute biomaterials (hybrid dental-resin, nano-filled composite, and zirconia ceramic) and comparatively study them. Goniometric measurements were made for four wavelengths in the visible range, allowing a spectral characterization of the materials studied. Previously, for each material, measurements were made with two different sample thicknesses at the same wavelength, checking the behaviour of the angular scattering profile. The asymmetry of experimental phase functions was considered in the recovery of the scattering anisotropy factor. The results demonstrate that the thicker sample yielded a less forward-directed scattering profile than did the thinner sample. The biomaterials analysed show angular scattering comparable to those of the tissues that they may replace. Comparisons can be made by virtue of the low uncertainties found.

  14. Biomaterial based modulation of macrophage polarization: a review and suggested design principles

    Directory of Open Access Journals (Sweden)

    Rukmani Sridharan


    Full Text Available Macrophages have long been known for their phagocytic capabilities and immune defence; however, their role in healing is being increasingly recognized in recent years due to their ability to polarize into pro-inflammatory and anti-inflammatory phenotypes. Historically, biomaterials were designed to be inert to minimize the host response. More recently, the emergence of tissue engineering and regenerative medicine has led to the design of biomaterials that interact with the host through tailored mechanical, chemical and temporal characteristics. Due to such advances in biomaterial functionality and an improved understanding of macrophage responses to implanted materials, it is now possible to identify biomaterial design characteristics that dictate the host response and contribute to successful tissue integration. Herein, we begin by briefly reviewing macrophage cell origin and the key cytokine/chemokine markers of macrophage polarization and then describe which responses are favorable for both replacement and regenerative biomaterials. The body of the review focuses on macrophage polarization in response to inherent cues directly provided by biomaterials and the consequent cues that result from events related to biomaterial implantation. To conclude, a section on potential design principles for both replacement and regenerative biomaterials is presented. An in depth understanding of biomaterial cues to selectively polarize macrophages may prove beneficial in the design of a new generation of ‘immuno-informed’ biomaterials that can positively interact with the immune system to dictate a favorable macrophage response following implantation.

  15. Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial

    Directory of Open Access Journals (Sweden)

    Jui-Yang Lai


    Full Text Available Hyaluronic acid (HA is one of the most important ophthalmic biomaterials, while also being used for tissue engineering and drug delivery. Although chemical cross-linking is an effective way to improve the material performance, it may as a consequence be detrimental to the living cells/tissues. Given that the cross-linking efficiency is mediated by the solvent composition during the chemical modification, this study aims to explore the stability and biocompatibility of carbodiimide cross-linked HA in relation to material processing conditions by varying the acetone/water volume ratio (from 70:30 to 95:5 at a constant 1-ethyl-3-(3-dimethyl aminopropyl carbodiimide (EDC concentration of 100 mM. Our results indicated that after the EDC treatment in the presence of an acetone/water mixture (85:15, v/v, the HA hydrogel membranes have the lowest equilibrium water content, the highest stress at break and the greatest resistance to hyaluronidase digestion. Live/Dead assays and pro-inflammatory cytokine expression analyses showed that the cross-linked HA hydrogel membranes, irrespective of the solvent composition, are compatible with human RPE cell lines without causing toxicity and inflammation. However, it should be noted that the test samples prepared by the cross-linking in the presence of acetone/water mixtures containing 70, 75, and 95 vol % of acetone slightly inhibit the metabolic activity of viable ARPE-19 cultures, probably due to the alteration in the ionic interaction between the medium nutrients and polysaccharide biomaterials. In summary, the water content, mechanical strength and RPE cell proliferative capacity strongly depends on the solvent composition for carbodiimide cross-linking of HA materials.

  16. Freezing-induced deformation of biomaterials in cryomedicine (United States)

    Ozcelikkale, Altug

    Cryomedicine utilizes low temperature treatments of biological proteins, cells and tissues for cryopreservation, materials processing and cryotherapy. Lack of proper understanding of cryodamage that occurs during these applications remains to be the primary bottleneck for development of successful tissue cryopreservation and cryosurgery procedures. An engineering approach based on a view of biological systems as functional biomaterials can help identify, predict and control the primary cryodamage mechanisms by developing an understanding of underlying freezing-induced biophysical processes. In particular, freezing constitutes the main structural/mechanical origin of cryodamage and results in significant deformation of biomaterials at multiple length scales. Understanding of these freezing-induced deformation processes and their effects on post-thaw biomaterial functionality is currently lacking but will be critical to engineer improved cryomedicine procedures. This dissertation addresses this problem by presenting three separate but related studies of freezing-induced deformation at multiple length scales including nanometer-scale protein fibrils, single cells and whole tissues. A combination of rigorous experimentation and computational modeling is used to characterize post-thaw biomaterial structure and properties, predict biomaterial behavior and assess its post-thaw biological functionality. Firstly, freezing-induced damage on hierarchical extracellular matrix structure of collagen is investigated at molecular, fibril and matrix levels. Results indicate to a specific kind of fibril damage due to freezing-induced expansion of intrafibrillar fluid. This is followed by a study of freezing-induced cell and tissue deformation coupled to osmotically driven cellular water transport. Computational and semi empirical modeling of these processes indicate that intracellular deformation of the cell during freezing is heterogeneous and can interfere with cellular water

  17. Interactions between biomaterials and the sclera: Implications on myopia progression (United States)

    Su, James

    Myopia prevalence has steadily climbed worldwide in recent decades with the most dramatic impact in East Asian countries. Treatments such as eyeglasses, contact lenses, and laser surgery for the refractive error are widely available, but none cures the underlying cause. In progressive high myopia, invasive surgical procedures using a scleral buckle for mechanical support are performed since the patient is at risk of becoming blind. The treatment outcome is highly dependent on the surgeon's skills and the patient's myopia progression rate, with limited choices in buckling materials. This dissertation, in four main studies, represents efforts made to control high myopia progression through the exploration and development of biomaterials that influence scleral growth. First, mRNA expression levels of the chick scleral matrix metalloproteinases, tissue-inhibitor of matrix metalloproteinases, and transforming growth factor-beta 2 were assessed for temporal and defocus power effects. The first study elucidated the roles that these factors play in scleral growth regulation and suggested potential motifs that can be incorporated in future biomaterials design. Second, poly(vinyl-pyrrolidone) as injectable gels and poly(2-hydroxyethyl methacrylate) as solid strips were implanted in chicks to demonstrate the concept of posterior pole scleral reinforcements. This second study found that placing appropriate biomaterials at the posterior pole of the eye could directly influence scleral remodeling by interacting with the host cells. Both studies advanced the idea that scleral tissue remodeling could be potentially controlled by well-designed biomaterials. These findings led to the exploration of biomimetic hydrogels comprising enzymatically-degradable semi-interpenetrating polymer networks (edsIPNs) to determine their biocompatibility and effects on the chick posterior eye wall. This third study demonstrated the feasibility of stimulating scleral growth by applying biomimetic

  18. The role of biomaterial properties in peri-implant neovascularization (United States)

    Raines, Andrew Lawrence

    An understanding of the interactions between orthopaedic and dental implant surfaces with the surrounding host tissue is critical in the design of next generation implants to improve osseointegration and clinical success rates. Critical to the process of osseointegration is the rapid establishment of a patent neovasculature in the peri-implant space to allow for the delivery of oxygen, nutrients, and progenitor cells. The central aim of this thesis is to understand how biomaterials regulate cellular and host tissue response to elicit a pro-angiogenic microenvironment at the implant/tissue interface. To address this question, the studies performed in this thesis aim to (1) determine whether biomaterial surface properties can modulate the production and secretion of pro-angiogenic growth factors by cells, (2) determine the role of integrin and VEGF-A signaling in the angiogenic response of cells to implant surface features, and (3) to determine whether neovascularization in response to an implanted biomaterial can be modulated in vivo. The results demonstrate that biomaterial surface microtopography and surface energy can increase the production of pro-angiogenic growth factors by osteoblasts and that these growth factors stimulate the differentiation of endothelial cells in a paracrine manner and the results suggest that signaling through specific integrin receptors affects the production of angiogenic growth factors by osteoblast-like cells. Further, using a novel in vivo model, the results demonstrate that a combination of a rough surface microtopography and high surface energy can improve bone-to-implant contact and neovascularization. The results of these studies also suggest that VEGF-A produced by osteoblast-like cells has both an autocrine and paracrine effect. VEGF-A silenced cells exhibited reduced production of both pro-angiogenic and osteogenic growth factors in response to surface microtopgraphy and surface energy, and conditioned media from VEGF

  19. p38 MAPK-Mediated Bmi-1 down-regulation and defective proliferation in ATM-deficient neural stem cells can be restored by Akt activation.

    Directory of Open Access Journals (Sweden)

    Jeesun Kim

    Full Text Available A-T (ataxia telangiectasia is a genetic disease caused by a mutation in the Atm (A-T mutated gene that leads to neurodegeneration. Despite an increase in the numbers of studies in this area in recent years, the mechanisms underlying neurodegeneration in human A-T are still poorly understood. Previous studies demonstrated that neural stem cells (NSCs isolated from the subventricular zone (SVZ of Atm(-/- mouse brains show defective self-renewal and proliferation, which is accompanied by activation of chronic p38 mitogen-activated protein kinase (MAPK and a lower level of the polycomb protein Bmi-1. However, the mechanism underlying Bmi-1 down-regulation and its relevance to defective proliferation in Atm(-/- NSCs remained unclear. Here, we show that over-expression of Bmi-1 increases self-renewal and proliferation of Atm(-/- NSCs to normal, indicating that defective proliferation in Atm(-/- NSCs is a consequence of down-regulation of Bmi-1. We also demonstrate that epidermal growth factor (EGF-induced Akt phosphorylation renders Bmi-1 resistant to the proteasomal degradation, leading to its stabilization and accumulation in the nucleus. However, inhibition of the Akt-dependent Bmi-1 stabilizing process by p38 MAPK signaling reduces the levels of Bmi-1. Treatment of the Atm(-/- NSCs with a specific p38 MAPK inhibitor SB203580 extended Bmi-1 posttranscriptional turnover and H2A ubiquitination in Atm(-/- NSCs. Our observations demonstrate the molecular basis underlying the impairment of self-renewal and proliferation in Atm(-/- NSCs through the p38 MAPK-Akt-Bmi-1-p21 signaling pathway.

  20. The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse. (United States)

    Sullivan, Chelsea S; Kümper, Maike; Temple, Brenda S; Maness, Patricia F


    Establishment of a proper balance of excitatory and inhibitory connectivity is achieved during development of cortical networks and adjusted through synaptic plasticity. The neural cell adhesion molecule (NCAM) and the receptor tyrosine kinase EphA3 regulate the perisomatic synapse density of inhibitory GABAergic interneurons in the mouse frontal cortex through ephrin-A5-induced growth cone collapse. In this study, it was demonstrated that binding of NCAM and EphA3 occurred between the NCAM Ig2 domain and EphA3 cysteine-rich domain (CRD). The binding interface was further refined through molecular modeling and mutagenesis and shown to be comprised of complementary charged residues in the NCAM Ig2 domain (Arg-156 and Lys-162) and the EphA3 CRD (Glu-248 and Glu-264). Ephrin-A5 induced co-clustering of surface-bound NCAM and EphA3 in GABAergic cortical interneurons in culture. Receptor clustering was impaired by a charge reversal mutation that disrupted NCAM/EphA3 association, emphasizing the importance of the NCAM/EphA3 binding interface for cluster formation. NCAM enhanced ephrin-A5-induced EphA3 autophosphorylation and activation of RhoA GTPase, indicating a role for NCAM in activating EphA3 signaling through clustering. NCAM-mediated clustering of EphA3 was essential for ephrin-A5-induced growth cone collapse in cortical GABAergic interneurons, and RhoA and a principal effector, Rho-associated protein kinase, mediated the collapse response. This study delineates a mechanism in which NCAM promotes ephrin-A5-dependent clustering of EphA3 through interaction of the NCAM Ig2 domain and the EphA3 CRD, stimulating EphA3 autophosphorylation and RhoA signaling necessary for growth cone repulsion in GABAergic interneurons in vitro, which may extend to remodeling of axonal terminals of interneurons in vivo.

  1. Testosterone affects neural gene expression differently in male and female juncos: a role for hormones in mediating sexual dimorphism and conflict.

    Directory of Open Access Journals (Sweden)

    Mark P Peterson

    Full Text Available Despite sharing much of their genomes, males and females are often highly dimorphic, reflecting at least in part the resolution of sexual conflict in response to sexually antagonistic selection. Sexual dimorphism arises owing to sex differences in gene expression, and steroid hormones are often invoked as a proximate cause of sexual dimorphism. Experimental elevation of androgens can modify behavior, physiology, and gene expression, but knowledge of the role of hormones remains incomplete, including how the sexes differ in gene expression in response to hormones. We addressed these questions in a bird species with a long history of behavioral endocrinological and ecological study, the dark-eyed junco (Junco hyemalis, using a custom microarray. Focusing on two brain regions involved in sexually dimorphic behavior and regulation of hormone secretion, we identified 651 genes that differed in expression by sex in medial amygdala and 611 in hypothalamus. Additionally, we treated individuals of each sex with testosterone implants and identified many genes that may be related to previously identified phenotypic effects of testosterone treatment. Some of these genes relate to previously identified effects of testosterone-treatment and suggest that the multiple effects of testosterone may be mediated by modifying the expression of a small number of genes. Notably, testosterone-treatment tended to alter expression of different genes in each sex: only 4 of the 527 genes identified as significant in one sex or the other were significantly differentially expressed in both sexes. Hormonally regulated gene expression is a key mechanism underlying sexual dimorphism, and our study identifies specific genes that may mediate some of these processes.

  2. In vivo Characterization of Amorphous Silicon Carbide As a Biomaterial for Chronic Neural Interfaces. (United States)

    Knaack, Gretchen L; McHail, Daniel G; Borda, German; Koo, Beomseo; Peixoto, Nathalia; Cogan, Stuart F; Dumas, Theodore C; Pancrazio, Joseph J


    Implantable microelectrode arrays (MEAs) offer clinical promise for prosthetic devices by enabling restoration of communication and control of artificial limbs. While proof-of-concept recordings from MEAs have been promising, work in animal models demonstrates that the obtained signals degrade over time. Both material robustness and tissue response are acknowledged to have a role in device lifetime. Amorphous Silicon carbide (a-SiC), a robust material that is corrosion resistant, has emerged as an alternative encapsulation layer for implantable devices. We systematically examined the impact of a-SiC coating on Si probes by immunohistochemical characterization of key markers implicated in tissue-device response. After implantation, we performed device capture immunohistochemical labeling of neurons, astrocytes, and activated microglia/macrophages after 4 and 8 weeks of implantation. Neuron loss and microglia activation were similar between Si and a-SiC coated probes, while tissue implanted with a-SiC displayed a reduction in astrocytes adjacent to the probe. These results suggest that a-SiC has a similar biocompatibility profile as Si, and may be suitable for implantable MEA applications as a hermetic coating to prevent material degradation.

  3. Frontiers in biomaterials the design, synthetic strategies and biocompatibility of polymer scaffolds for biomedical application

    CERN Document Server

    Cao, Shunsheng


    Frontiers in Biomaterials: The Design, Synthetic Strategies and Biocompatibility of Polymer Scaffolds for Biomedical Application, Volume 1" highlights the importance of biomaterials and their interaction with biological system. The need for the development of biomaterials as scaffold for tissue regeneration is driven by the increasing demands for materials that mimic functions of extracellular matrices of body tissues.This ebook covers the latest challenges on the biocompatibility of scaffold overtime after implantation and discusses the requirement of innovative technologies and strategies f

  4. [Current requirements for polymeric biomaterials in ear, nose and throat medicine]. (United States)

    Sternberg, K


    In recent years the ear, nose and throat medicine (ENT medicine) has been stimulated by numerous innovations in the field of implants which are based on new biomaterials and modern implant technologies. In this context, biomaterials integrated in living organisms have to allow for the technical requirements and the biological interactions between the implant and the tissue. With regard to their suitability, functional capability of the implant, which is complementary to the mechanical implant properties, sufficient stability against physiological media, as well as high biocompatibility are to be demanded. Another purpose of the use of biomaterials is the maintenance and the enhancement of biofunctionality over a long time period. These general requirements for biomaterials also have their validity in ENT medicine. Different materials are applied as biomaterials. Metals belong to the oldest biomaterials. In addition, alloys, ceramics, inorganic glasses and composites were tested. Furthermore, natural and synthetic polymers, which are primarily presented in this article regarding their properties and their applications as materials for cochlear implants, osteosynthesis implants, stents and novel scaffolds for tissue engineering, are increasingly applied. According to their use in permanent and temporary implants, polymers are to be differentiated between biostable and biodegradable polymers. The presented general and current requirements for biomaterials and biomaterial applications in ENT medicine demonstrate key aspects of the current biomaterial research in this field. They do as well document the high impact of the interdisciplinary collaboration of natural and medical scientists and engineers.

  5. Mechanical behavior of hydroxyapatite biomaterials: an experimentally validated micromechanical model for elasticity and strength. (United States)

    Fritsch, Andreas; Dormieux, Luc; Hellmich, Christian; Sanahuja, Julien


    Hydroxyapatite (HA) biomaterials production has been a major field in biomaterials science and biomechanical engineering. As concerns prediction of their stiffness and strength, we propose to go beyond statistical correlations with porosity or empirical structure-property relationships, as to resolve the material-immanent microstructures governing the overall mechanical behavior. The macroscopic mechanical properties are estimated from the microstructures of the materials and their composition, in a homogenization process based on continuum micromechanics. Thereby, biomaterials are envisioned as porous polycrystals consisting of HA needles and spherical pores. Validation of respective micromechanical models relies on two independent experimental sets: biomaterial-specific macroscopic (homogenized) stiffness and uniaxial (tensile and compressive) strength predicted from biomaterial-specific porosities, on the basis of biomaterial-independent ("universal") elastic and strength properties of HA, are compared with corresponding biomaterial-specific experimentally determined (acoustic and mechanical) stiffness and strength values. The good agreement between model predictions and the corresponding experiments underlines the potential of micromechanical modeling in improving biomaterial design, through optimization of key parameters such as porosities or geometries of microstructures, in order to reach the desired values for biomaterial stiffness or strength.


    Energy Technology Data Exchange (ETDEWEB)

    Brigmon, R.; Narayan, R.; Adiga, S.; Pellin, M.; Curtiss, L.; Stafslien, S.; Chisholm, B.; Monteiro-Riviere, N.; Elam, J.


    Due to its chemical stability, uniform pore size, and high pore density, nanoporous alumina is being investigated for use in biosensing, drug delivery, hemodialysis, and other medical applications. In recent work, we have examined the use of atomic layer deposition for coating the surfaces of nanoporous alumina membranes. Zinc oxide coatings were deposited on nanoporous alumina membranes using atomic layer deposition. The zinc oxide-coated nanoporous alumina membranes demonstrated antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria. These results suggest that atomic layer deposition is an attractive technique for modifying the surfaces of nanoporous alumina membranes and other nanostructured biomaterials.

  7. Novel biomaterials decontamination of toxic metals from wastewater

    CERN Document Server

    Srivastava, Shalini


    Current research revolves around trends to bring technology into harmony with the natural environment and in order to protect the ecosystem. Bioremediation involves processes which reduce the overall treatment costs by using agricultural residues. Regeneration of the biosorbent further increases the cost effectiveness of the process, thus warranting its future success in solving water quality problems. Special emphasis is paid to chemical modifications resulting in tailored novel biomaterials which improve its sorption efficiency and environmental stability. In this way it can be used commerci

  8. Evaluation of Biomaterials Using Micro-Computerized Tomography (United States)

    Torris, A. T. Arun; Columbus, K. C. Soumya; Saaj, U. S.; Nair, Manitha B.; Krishnan, Kalliyana V.


    Micro-computed tomography or Micro-CT is a high resolution, non-invasive, x-ray scanning technique that allows precise three-dimensional imaging and quantification of micro-architectural and structural parameters of objects. Tomographic reconstruction is based on a cone-beam convolution-back-projection algorithm. Micro-architectural and structural parameters such as porosity, surface area to volume ratio, interconnectivity, pore size, wall thickness, anisotropy and cross-section area of biomaterials and bio-specimens such as trabecular bone, polymer scaffold, bio-ceramics and dental restorative were evaluated through imaging and computer aided manipulation of the object scan data sets.

  9. Fracture Toughness Properties of Three Different Biomaterials Measured by Nanoindentation

    Institute of Scientific and Technical Information of China (English)

    Ji-yu Sun; Jin Tong


    The fracture toughness of hard biomaterials,such as nacre,bovine hoof wall and beetle cuticle,is associated with fibrous or lamellar structures that deflect or stop growing cracks.Their hardness and reduced modulus were measured by using a nanoindenter in this paper.Micro/nanoscale cracks were generated by nanoindentation using a Berkovich tip.Nanoindentation of nacre and bovine hoof wall resulted in pile-up around the indent.It was found that the fracture toughness(Kc)of bovine hoof wall is the maximum,the second is nacre,and the elytra cuticle of dung beetle is the least one.

  10. Scattering and Absorption Properties of Biomaterials for Dental Restorative Applications (United States)

    Fernandez-Oliveras, A.; Rubiño, M.; Pérez, M. M.


    The physical understanding of the optical properties of dental biomaterials is mandatory for their final success in restorative applications.Light propagation in biological media is characterized by the absorption coefficient, the scattering coefficient, the scattering phase function,the refractive index, and the surface conditions (roughness). We have employed the inverse adding-doubling (IAD) method to combine transmittance and reflectance measurements performed using an integrating-sphere setup with the results of the previous scattering-anisotropygoniometric measurements. This has led to the determination of the absorption and the scattering coefficients. The aim was to optically characterize two different dental-resin composites (nanocomposite and hybrid) and one type of zirconia ceramic, and comparatively study them. The experimental procedure was conducted under repeatability conditions of measurement in order to determine the uncertainty associated to the optical properties of the biomaterials. Spectral variations of the refraction index and the scattering anisotropy factor were also considered. The whole experimental procedure fulfilled all the necessary requirements to provide optical-property values with lower associated uncertainties. The effective transport coefficient presented a similar spectral behavior for the two composites but completely different for the zirconia ceramic. The results demonstrated that the scattering anisotropy exerted a clearly distinct impact on the optical properties of the zirconia ceramic compared with those of the dental-resin composites.

  11. Biomaterial Scaffolds with Biomimetic Fluidic Channels for Hepatocyte Culture

    Institute of Scientific and Technical Information of China (English)

    Xiao Li; Jiankang He; Yaxiong Liu; Qian Zhao; Wanquan Wu; Dichen Li; Zhongmin Jin


    Biomaterial scaffolds play an important role in maintaining the viability and biological functions of highly metabolic hepatocytes in liver tissue engineering.One of the major challenges involves building a complex microchannel network inside three-dimensional (3D) scaffolds for efficient mass transportation.Here we presented a biomimetic strategy to generate a microchannel network within porous biomaterial scaffolds by mimicking the vascular tree of rat liver.The typical parameters of the blood vessels were incorporated into the biomimetic design of the microchannel network such as branching angle and diameter.Silk fibroin-gelatin scaffolds with biomimetic vascular tree were fabricated by combining micromolding,freeze drying and 3D rolling techniques.The relationship between the micro-channeled design and flow pattern was revealed by a flow experiment,which indicated that the scaffolds with biomimetic vascular tree exhibited unique capability in improving mass transportation inside the 3D scaffold.The 3D scaffolds,preseeded with primary hepatocytes,were dynamically cultured in a bioreactor system.The results confirmed that the pre-designed biomimetic microchannel network facilitated the generation and expansion of hepatocytes.

  12. Dielectric Behavior of Biomaterials at Different Frequencies on Room Temperature (United States)

    Shrivastava, B. D.; Barde, Ravindra; Mishra, A.; Phadke, S.


    Propagation of electromagnetic (EM) waves in radiofrequency (RF) and microwave systems is described mathematically by Maxwell's equations with corresponding boundary conditions. Dielectric properties of lossless and lossy materials influence EM field distribution. For a better understanding of the physical processes associated with various RF and microwave devices, it is necessary to know the dielectric properties of media that interact with EM waves. For telecommunication and radar devices, variations of complex dielectric permittivity (referring to the dielectric property) over a wide frequency range are important. For RF and microwave applicators intended for thermal treatments of different materials at ISM (industrial, scientific, medical) frequencies, one needs to study temperature and moisture content dependencies of the Permittivity of the treated materials. Many techniques have been developed for the measurement of materials. In the present paper authors used Bones and scales of Fish taken from Narmada River (Rajghat Dist. Barwani) as biomaterials. Dielectric properties of Biomaterials with the frequency range from 1Hz to 10 MHz at room temperature with low water content were measured by in-situ performance dielectric kit. Analysis has been done by Alpha high performance impedance analyzer and LCR meters. The experimental work were carried out in Inter University Consortium UGC-DAE, CSR center Indore MP. Measured value indicates the dielectric constant (ɛ') dielectric loss (ɛ") decreases with increasing frequency while conductivity (σ) increases with frequency increased.

  13. Study of novel rosin-based biomaterials for pharmaceutical coating. (United States)

    Fulzele, Suniket V; Satturwar, Prashant M; Dorle, Avinash K


    The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Young's modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young's modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations. Diclofenac sodium-layered pellets coated with GMR and PMR film formulations showed sustained drug release for up to 10 hours. The release rate was influenced by the extent of plasticization and coating level. The results obtained in the study demonstrate the utility of novel rosin-based biomaterials for pharmaceutical coating and sustained-release drug delivery systems.

  14. Improving the clinical impact of biomaterials in cancer immunotherapy. (United States)

    Gammon, Joshua M; Dold, Neil M; Jewell, Christopher M


    Immunotherapies for cancer have progressed enormously over the past few decades, and hold great promise for the future. The successes of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumors. However, the effectiveness of current immunotherapies is limited by hurdles ranging from immunosuppressive strategies employed by tumors, to inadequate specificity of existing therapies, to heterogeneity of disease. Further, the vast majority of approved immunotherapies employ systemic delivery of immunomodulators or cells that make addressing some of these challenges more difficult. Natural and synthetic biomaterials - such as biocompatible polymers, self-assembled lipid particles, and implantable biodegradable devices - offer unique potential to address these hurdles by harnessing the benefits of therapeutic targeting, tissue engineering, co-delivery, controlled release, and sensing. However, despite the enormous investment in new materials and nanotechnology, translation of these ideas to the clinic is still an uncommon outcome. Here we review the major challenges facing immunotherapies and discuss how the newest biomaterials and nanotechnologies could help overcome these challenges to create new clinical options for patients.

  15. Nanomechanics of Cells and Biomaterials Studied by Atomic Force Microscopy. (United States)

    Kilpatrick, Jason I; Revenko, Irène; Rodriguez, Brian J


    The behavior and mechanical properties of cells are strongly dependent on the biochemical and biomechanical properties of their microenvironment. Thus, understanding the mechanical properties of cells, extracellular matrices, and biomaterials is key to understanding cell function and to develop new materials with tailored mechanical properties for tissue engineering and regenerative medicine applications. Atomic force microscopy (AFM) has emerged as an indispensable technique for measuring the mechanical properties of biomaterials and cells with high spatial resolution and force sensitivity within physiologically relevant environments and timescales in the kPa to GPa elastic modulus range. The growing interest in this field of bionanomechanics has been accompanied by an expanding array of models to describe the complexity of indentation of hierarchical biological samples. Furthermore, the integration of AFM with optical microscopy techniques has further opened the door to a wide range of mechanotransduction studies. In recent years, new multidimensional and multiharmonic AFM approaches for mapping mechanical properties have been developed, which allow the rapid determination of, for example, cell elasticity. This Progress Report provides an introduction and practical guide to making AFM-based nanomechanical measurements of cells and surfaces for tissue engineering applications.

  16. Teaching technological innovation and entrepreneurship in polymeric biomaterials. (United States)

    Washburn, Newell R


    A model for incorporating an entrepreneurship module has been developed in an upper-division and graduate-level engineering elective on Polymeric Biomaterials (27-311/42-311/27-711/42-711) at Carnegie Mellon University. A combination of lectures, assignments, and a team-based project were used to provide students with a framework for applying their technical skills in the development of new technologies and a basic understanding of the issues related to translational research and technology commercialization. The specific approach to the project established in the course, which represented 20% of the students' grades, and the grading rubric for each of the milestones are described along with suggestions for generalizing this approach to different applications of biomaterials or other engineering electives. Incorporating this model of entrepreneurship into electives teaches students course content within the framework of technological innovation and many of the concepts and tools need to practice it. For students with situational or individual interest in the project, it would also serve to deepen their understanding of the traditional course components as well as provide a foundation for integrating technological innovation and lifelong learning.

  17. Cell-based detection of microbial biomaterial contaminations. (United States)

    Roch, Toralf; Ma, Nan; Kratz, Karl; Lendlein, Andreas


    A major challenge in biomaterial synthesis and functionalization is the prevention of microbial contaminations such as endotoxins (lipopolysaccharides (LPS)). In addition to LPS, which are exclusively expressed by Gram negative bacteria, also other microbial products derived from fungi or Gram positive bacteria can be found as contaminations in research laboratories. Typically, the Limulus amebocyte lysate (LAL)-test is used to determine the endotoxin levels of medical devices. However, this test fails to detect material-bound LPS and other microbial contaminations and, as demonstrated in this study, detects LPS from various bacterial species with different sensitivities.In this work, a cell-based assay using genetically engineered RAW macrophages, which detect not only soluble but also material-bound microbial contaminations is introduced.The sensitivity of this cell-line towards different LPS species and different heat-inactivated microbes was investigated. As proof of principle a soft hydrophobic poly(n-butyl acrylate) network (cPnBA), which may due to adhesive properties strongly bind microbes, was deliberately contaminated with heat-inactivated bacteria. While the LAL-test failed to detect the microbial contamination, the cell-based assay clearly detected material-bound microbial contaminations. Our data demonstrate that a cell-based detection system should routinely be used as supplement to the LAL-test to determine microbial contaminations of biomaterials.

  18. Molecular manipulation of microstructures: biomaterials, ceramics, and semiconductors. (United States)

    Stupp, S I; Braun, P V


    Organic molecules can alter inorganic microstructures, offering a very powerful tool for the design of novel materials. In biological systems, this tool is often used to create microstructures in which the organic manipulators are a minority component. Three groups of materials-biomaterials, ceramics, and semiconductors-have been selected to illustrate this concept as used by nature and by synthetic laboratories exploring its potential in materials technology. In some of nature's biomaterials, macromolecules such as proteins, glycoproteins, and polysaccharides are used to control nucleation and growth of mineral phases and thus manipulate microstructure and physical properties. This concept has been used synthetically to generate apatite-based materials that can function as artificial bone in humans. Synthetic polymers and surfactants can also drastically change the morphology of ceramic particles, impart new functional properties, and provide new processing methods for the formation of useful objects. Interesting opportunities also exist in creating semiconducting materials in which molecular manipulators connect quantum dots or template cavities, which change their electronic properties and functionality.

  19. Arsenic removal using natural biomaterial-based sorbents. (United States)

    Ansone, Linda; Klavins, Maris; Viksna, Arturs


    Arsenic contamination of water is a major problem worldwide. A possible solution can be approached through developing new sorbents based on cost-effective and environmentally friendly natural biomaterials. We have developed new sorbents based on biomaterial impregnation with iron oxyhydroxide. In this study, raw peat material, iron-modified peat, iron-modified biomass (shingles, straw, sands, cane and moss) as well as iron humate were used for the removal of arsenate from contaminated water. The highest sorption capacity was observed in iron-modified peat, and kinetic studies indicated that the amount of arsenic sorbed on this material exceeds 90 % in 5 h. Arsenate sorption on iron-modified peat is characterised by the pseudo-second-order mechanism. The results of arsenic sorption in the presence of competing substances indicated that sulphate, nitrate, chloride and tartrate anions have practically no influence on As(V) sorption onto Fe-modified peat, whereas the presence of phosphate ions and humic acid significantly lowers the arsenic removal efficiency.

  20. Generation of Viable Cell and Biomaterial Patterns by Laser Transfer (United States)

    Ringeisen, Bradley


    In order to fabricate and interface biological systems for next generation applications such as biosensors, protein recognition microarrays, and engineered tissues, it is imperative to have a method of accurately and rapidly depositing different active biomaterials in patterns or layered structures. Ideally, the biomaterial structures would also be compatible with many different substrates including technologically relevant platforms such as electronic circuits or various detection devices. We have developed a novel laser-based technique, termed matrix assisted pulsed laser evaporation direct write (MAPLE DW), that is able to direct write patterns and three-dimensional structures of numerous biologically active species ranging from proteins and antibodies to living cells. Specifically, we have shown that MAPLE DW is capable of forming mesoscopic patterns of living prokaryotic cells (E. coli bacteria), living mammalian cells (Chinese hamster ovaries), active proteins (biotinylated bovine serum albumin, horse radish peroxidase), and antibodies specific to a variety of classes of cancer related proteins including intracellular and extracellular matrix proteins, signaling proteins, cell cycle proteins, growth factors, and growth factor receptors. In addition, patterns of viable cells and active biomolecules were deposited on different substrates including metals, semiconductors, nutrient agar, and functionalized glass slides. We will present an explanation of the laser-based transfer mechanism as well as results from our recent efforts to fabricate protein recognition microarrays and tissue-based microfluidic networks.




    ABSTRACT Objective: Based on a literature review and on our own experience, this study proposes sheep as an experimental model to evaluate the bioactive capacity of bone substitute biomaterials, dental implant systems and orthopedics devices. The literature review covered relevant databases available on the Internet from 1990 until to date, and was supplemented by our own experience. Methods: For its resemblance in size and weight to humans, sheep are quite suitable for use as an experimental model. However, information about their utility as an experimental model is limited. The different stages involving sheep experiments were discussed, including the care during breeding and maintenance of the animals obtaining specimens for laboratory processing, and highlighting the unnecessary euthanasia of animals at the end of study, in accordance to the guidelines of the 3Rs Program. Results: All experiments have been completed without any complications regarding the animals and allowed us to evaluate hypotheses and explain their mechanisms. Conclusion: The sheep is an excellent animal model for evaluation of biomaterial for bone regeneration and dental implant osseointegration. From an ethical point of view, one sheep allows for up to 12 implants per animal, permitting to keep them alive at the end of the experiments. Level of Evidence II, Retrospective Study. PMID:28149193

  2. Biomaterials for periodontal regeneration: a review of ceramics and polymers. (United States)

    Shue, Li; Yufeng, Zhang; Mony, Ullas


    Periodontal disease is characterized by the destruction of periodontal tissues. Various methods of regenerative periodontal therapy, including the use of barrier membranes, bone replacement grafts, growth factors and the combination of these procedures have been investigated. The development of biomaterials for tissue engineering has considerably improved the available treatment options above. They fall into two broad classes: ceramics and polymers. The available ceramic-based materials include calcium phosphate (eg, tricalcium phosphate and hydroxyapatite), calcium sulfate and bioactive glass. The bioactive glass bonds to the bone with the formation of a layer of carbonated hydroxyapatite in situ. The natural polymers include modified polysaccharides (eg, chitosan,) and polypeptides (collagen and gelatin). Synthetic polymers [eg, poly(glycolic acid), poly(L-lactic acid)] provide a platform for exhibiting the biomechanical properties of scaffolds in tissue engineering. The materials usually work as osteogenic, osteoconductive and osteoinductive scaffolds. Polymers are more widely used as a barrier material in guided tissue regeneration (GTR). They are shown to exclude epithelial downgrowth and allow periodontal ligament and alveolar bone cells to repopulate the defect. An attempt to overcome the problems related to a collapse of the barrier membrane in GTR or epithelial downgrowth is the use of a combination of barrier membranes and grafting materials. This article reviews various biomaterials including scaffolds and membranes used for periodontal treatment and their impacts on the experimental or clinical management of periodontal defect.

  3. How is the biocompatibilty of dental biomaterials evaluated? (United States)

    Murray, Peter E; García Godoy, Cristina; García Godoy, Franklin


    All biomaterials used in dentistry must be evaluated for biocompatibility using screening assays to protect patient health and safety. The purpose of this review is to explain the international biocompatibility guidelines, and to explain the structure of a test program. The test program requires the structured assessment of materials into four phases; general toxicity, local tissue irritation, pre-clinical, and clinical evaluation. Different types of screening assays are available, and it is important to understand the advantages and limitations of the various types of assays that are available, so that they can be selected for appropriateness and interpreted accurately. New scientific advances in terms of the chemical properties of dental materials, tissue engineering, stem cell, genetic transfer, biomaterial, and growth factor therapies are under development. These new therapies create improved opportunities to restore and regenerate oral tissues, but they can also present new hazards to patients. Prior to their clinical use, these new technologies must be proven to be safe, and not hazardous to human health. A structured biocompatibility assessment and advice on the selection of assays are outlined to evaluate these new therapies.

  4. Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model

    NARCIS (Netherlands)

    Fisher, J.P.; Lalani, Z.; Bossano, C.M.; Brey, E.M.; Demian, N.; Johnston, C.M.; Dean, D.; Jansen, J.A.; Wong, M.E.; Mikos, A.G.


    In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion.

  5. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives

    Directory of Open Access Journals (Sweden)

    Esther Reina-Romo


    Full Text Available Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields.

  6. Cell-Biomaterial Mechanical Interaction in the Framework of Tissue Engineering: Insights, Computational Modeling and Perspectives (United States)

    Sanz-Herrera, Jose A.; Reina-Romo, Esther


    Tissue engineering is an emerging field of research which combines the use of cell-seeded biomaterials both in vitro and/or in vivo with the aim of promoting new tissue formation or regeneration. In this context, how cells colonize and interact with the biomaterial is critical in order to get a functional tissue engineering product. Cell-biomaterial interaction is referred to here as the phenomenon involved in adherent cells attachment to the biomaterial surface, and their related cell functions such as growth, differentiation, migration or apoptosis. This process is inherently complex in nature involving many physico-chemical events which take place at different scales ranging from molecular to cell body (organelle) levels. Moreover, it has been demonstrated that the mechanical environment at the cell-biomaterial location may play an important role in the subsequent cell function, which remains to be elucidated. In this paper, the state-of-the-art research in the physics and mechanics of cell-biomaterial interaction is reviewed with an emphasis on focal adhesions. The paper is focused on the different models developed at different scales available to simulate certain features of cell-biomaterial interaction. A proper understanding of cell-biomaterial interaction, as well as the development of predictive models in this sense, may add some light in tissue engineering and regenerative medicine fields. PMID:22174660

  7. The foreign body reaction to a biodegradable biomaterial differs between rats and mice

    NARCIS (Netherlands)

    Khouw, IMSL; van Wachem, PB; Molema, G; Plantinga, JA; de Leij, LFMH; van Luyn, MJA


    Before a biomaterial can be applied in the clinic, biocompatibility must be tested in in vivo models, by monitoring the foreign body reaction. In this study, we compared the foreign body reaction (EBR) to the biodegradable biomaterial hexamethylenediisocyanate crosslinked dermal sheep collagen (HDSC

  8. Positively charged biomaterials exert antimicrobial effects on gram-negative bacilli in rats

    NARCIS (Netherlands)

    Gottenbos, B; van der Mei, HC; Klatter, F; Grijpma, DW; Feijen, J; Nieuwenhuis, P; Busscher, HJ


    Biomaterial-centered infection is a much-dreaded complication associated with the use of biomedical implants. Although positively charged biomaterial surfaces stimulate bacterial adhesion, it has been suggested that surface growth of adhering Gram-negative bacilli is inhibited on positively charged

  9. Western blotting as a method for studying cell-biomaterial interactions : The role of protein collection

    NARCIS (Netherlands)

    van Kooten, TG; Klein, CL; Kirkpatrick, CJ


    Research of cell-biomaterial interactions is building on knowledge and methods available in cell and molecular biology. Western blotting is one of the options to characterize protein expression in cell populations. Method transfer to biomaterial model systems is not trivial because of the structure

  10. Neural Networks

    Directory of Open Access Journals (Sweden)

    Schwindling Jerome


    Full Text Available This course presents an overview of the concepts of the neural networks and their aplication in the framework of High energy physics analyses. After a brief introduction on the concept of neural networks, the concept is explained in the frame of neuro-biology, introducing the concept of multi-layer perceptron, learning and their use as data classifer. The concept is then presented in a second part using in more details the mathematical approach focussing on typical use cases faced in particle physics. Finally, the last part presents the best way to use such statistical tools in view of event classifers, putting the emphasis on the setup of the multi-layer perceptron. The full article (15 p. corresponding to this lecture is written in french and is provided in the proceedings of the book SOS 2008.

  11. In vitro evaluation of three different biomaterials as scaffolds for canine mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Oduvaldo Câmara Marques Pereira-Junior


    Full Text Available PURPOSE: To evaluate in vitro ability the of three different biomaterials - purified hydroxyapatite, demineralized bone matrix and castor oil-based polyurethane - as biocompatible 3D scaffolds for canine bone marrow mesenchymal stem cell (MSC intending bone tissue engineering. METHODS: MSCs were isolated from canine bone marrow, characterized and cultivated for seven days with the biomaterials. Cell proliferation and adhesion to the biomaterial surface were evaluated by scanning electron microscopy while differentiation into osteogenic lineage was evaluated by Alizarin Red staining and Sp7/Osterix surface antibody marker. RESULTS: The biomaterials allowed cellular growth, attachment and proliferation. Osteogenic differentiation occurred in the presence of hydroxyapatite, and matrix deposition commenced in the presence of the castor oil-based polyurethane. CONCLUSION: All the tested biomaterials may be used as mesenchymal stem cell scaffolds in cell-based orthopedic reconstructive therapy.

  12. [The influence of cell surface hydrophobicity Candida sp. on biofilm formation on different biomaterials]. (United States)

    Ciok-Pater, Emilia; Gospodarek, Eugenia; Prazyńska, Małgorzata; Bogiel, Tomasz


    The ability of yeasts to form biofilm is believed to play an important role in patomechanism of fungal infection. Candida sp. is considered to form biofilm on surfaces of biomaterials used in production of catheters, drains and prosthesis. Therefore this may lead to serious problems in patients with biomaterials used for diagnostic or therapeutic purposes. The aim of the study was to evaluate the influence of cell surface hydrophobicity (CSH) of Candida sp. on biofilm formation on different biomaterials. CSH was evaluated by two methods: Salt Aggregation Test (SAT) and Microbe Adhesion to Hydrocarbon Test (MATH). Biofilm formation on different biomaterials was measured by Richard's method after 72 hour incubation at 37 degrees C. Candida biofilm formation occurred more frequently in case of strains exhibiting hydrophobic than hydrophilic properties of cell surface. The statistically significant correlation between CSH and ability of biofilm formation on different biomaterials was observed (p < 0.05).

  13. Efficient surface modification of biomaterial to prevent biofilm formation and the attachment of microorganisms. (United States)

    Bazaka, Kateryna; Jacob, Mohan V; Crawford, Russell J; Ivanova, Elena P


    Biomaterials play a fundamental role in disease management and the improvement of health care. In recent years, there has been a significant growth in the diversity, function, and number of biomaterials used worldwide. Yet, attachment of pathogenic microorganisms onto biomaterial surfaces remains a significant challenge that substantially undermines their clinical applicability, limiting the advancement of these systems. The emergence and escalating pervasiveness of antibiotic-resistant bacterial strains makes the management of biomaterial-associated nosocomial infections increasingly difficult. The conventional post-operative treatment of implant-caused infections using systemic antibiotics is often marginally effective, further accelerating the extent of antimicrobial resistance. Methods by which the initial stages of bacterial attachment and biofilm formation can be restricted or prevented are therefore sought. The surface modification of biomaterials has the potential to alleviate pathogenic biofouling, therefore preventing the need for conventional antibiotics to be applied.

  14. Distinct enhancers at the Pax3 locus can function redundantly to regulate neural tube and neural crest expressions. (United States)

    Degenhardt, Karl R; Milewski, Rita C; Padmanabhan, Arun; Miller, Mayumi; Singh, Manvendra K; Lang, Deborah; Engleka, Kurt A; Wu, Meilin; Li, Jun; Zhou, Diane; Antonucci, Nicole; Li, Li; Epstein, Jonathan A


    Pax3 is a transcription factor expressed in somitic mesoderm, dorsal neural tube and pre-migratory neural crest during embryonic development. We have previously identified cis-acting enhancer elements within the proximal upstream genomic region of Pax3 that are sufficient to direct functional expression of Pax3 in neural crest. These elements direct expression of a reporter gene to pre-migratory neural crest in transgenic mice, and transgenic expression of a Pax3 cDNA using these elements is sufficient to rescue neural crest development in mice otherwise lacking endogenous Pax3. We show here that deletion of these enhancer sequences by homologous recombination is insufficient to abrogate neural crest expression of Pax3 and results in viable mice. We identify a distinct enhancer in the fourth intron that is also capable of mediating neural crest expression in transgenic mice and zebrafish. Our analysis suggests the existence of functionally redundant neural crest enhancer modules for Pax3.

  15. FGF Signaling Transforms Non-neural Ectoderm into Neural Crest


    Yardley, Nathan; García-Castro, Martín I.


    The neural crest arises at the border between the neural plate and the adjacent non-neural ectoderm. It has been suggested that both neural and non-neural ectoderm can contribute to the neural crest. Several studies have examined the molecular mechanisms that regulate neural crest induction in neuralized tissues or the neural plate border. Here, using the chick as a model system, we address the molecular mechanisms by which non-neural ectoderm generates neural crest. We report that in respons...

  16. Phenotype and polarization of autologous T cells by biomaterial-treated dendritic cells. (United States)

    Park, Jaehyung; Gerber, Michael H; Babensee, Julia E


    Given the central role of dendritic cells (DCs) in directing T-cell phenotypes, the ability of biomaterial-treated DCs to dictate autologous T-cell phenotype was investigated. In this study, we demonstrate that differentially biomaterial-treated DCs differentially directed autologous T-cell phenotype and polarization, depending on the biomaterial used to pretreat the DCs. Immature DCs (iDCs) were derived from human peripheral blood monocytes and treated with biomaterial films of alginate, agarose, chitosan, hyaluronic acid, or 75:25 poly(lactic-co-glycolic acid) (PLGA), followed by co-culture of these biomaterial-treated DCs and autologous T cells. When autologous T cells were co-cultured with DCs treated with biomaterial film/antigen (ovalbumin, OVA) combinations, different biomaterial films induced differential levels of T-cell marker (CD4, CD8, CD25, CD69) expression, as well as differential cytokine profiles [interferon (IFN)-γ, interleukin (IL)-12p70, IL-10, IL-4] in the polarization of T helper (Th) types. Dendritic cells treated with agarose films/OVA induced CD4+CD25+FoxP3+ (T regulatory cells) expression, comparable to untreated iDCs, on autologous T cells in the DC-T co-culture system. Furthermore, in this co-culture, agarose treatment induced release of IL-12p70 and IL-10 at higher levels as compared with DC treatment with other biomaterial films/OVA, suggesting Th1 and Th2 polarization, respectively. Dendritic cells treated with PLGA film/OVA treatment induced release of IFN-γ at higher levels compared with that observed for co-cultures with iDCs or DCs treated with all other biomaterial films. These results indicate that DC treatment with different biomaterial films has potential as a tool for immunomodulation by directing autologous T-cell responses.

  17. Directional conductivity in SWNT-collagen-fibrin composite biomaterials through strain-induced matrix alignment. (United States)

    Voge, Christopher M; Kariolis, Mihalis; MacDonald, Rebecca A; Stegemann, Jan P


    Composite biomaterials incorporating fibroblast cells, collagen Type I, fibrin, and 2 wt % carboxylated SWNT were created, and their properties were compared with similar control constructs without SWNT. Alignment of the matrix was stimulated by application of 8% cyclic strain for three 12-h periods over three days. All constructs underwent cell-mediated gel compaction to 15-20% of their initial volume, which was not affected by SWNT loading. Mechanical strain increased the rate of compaction, and strained constructs were significantly more compacted than unstrained controls by day 3. Cell viability and morphology were similar in both control and SWNT-loaded constructs, but unstrained samples exhibited a more stellate appearance with more numerous cellular projections. Application of mechanical strain caused clear alignment of both the cells and matrix in the direction of the applied strain. Bioimpedance measurements showed that SWNT loading increased the electrical conductivity of composite constructs, and that mechanically-induced alignment of the matrix/SWNT caused a further increase in conductivity. These results demonstrate that SWNT can be used to augment the electrical properties of 3D protein hydrogels, and that anisotropy in the matrix further enhances these properties. Such electrically conductive biopolymers may have a variety of applications in tissue engineering and biosensor development.

  18. Antimicrobial Biomaterials based on Single-Walled Carbon Nanotubes (United States)

    Aslan, Seyma

    Biomaterials that inactivate bacteria are needed to eliminate medical device infections. We investigate the antimicrobial nature of single-walled carbon nanotubes (SWNT) incorporated within biomedical polymers. In the first part, we focus on SWNT dispersed in the common biomedical polymer poly(lactic-co-glycolic acid) (PLGA) as a potential antimicrobial biomaterial. We find Escherichia coli and Staphylococcus epidermidis viability and metabolic activity to be significantly diminished in the presence of SWNT-PLGA, and to correlate with SWNT length and concentration. Up to 98 % of bacteria die within one hour of SWNT-PLGA versus 15-20% on pure PLGA. Shorter SWNT are found to be more toxic, possibly due to an increased density of open tube ends. In the second part, we investigate the antimicrobial activity of SWNT layer-by-layer (LbL) assembled with the polyelectrolytes poly(L-lysine) (PLL) and poly(L-glutamic acid) (PGA). The dispersibility of SWNT in aqueous solution is significantly improved via the biocompatible nonionic surfactant polyoxyethylene(20)sorbitan monolaurate (Tween 20) and the amphiphilic polymer phospholipid-poly(ethylene glycol) (PL-PEG). Absorbance spectroscopy and transmission electron microscopy (TEM) show SWNT with either Tween 20 or PL-PEG in aqueous solution to be well dispersed. Quartz crystal microgravimetry with dissipation (QCMD) measurements show both SWNT-Tween and SWNT-PL-PEG to LbL assemble with PLL and PGA into multilayer films, with the PL-PEG system yielding the greater final SWNT content. Bacterial inactivation rates are significantly higher (up to 90%) upon 24 hour incubation with SWNT containing films, compared to control films (ca. 20%). In the third part, we study the influence of bundling on the LbL assembly of SWNT with charged polymers, and on the antimicrobial properties of the assembled film. QCMD measurements show the bundled SWNT system to adsorb in an unusually strong fashion—to an extent three times greater than that

  19. Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine (United States)

    Chien, Karen B.

    Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood

  20. Selective Manipulation of Neural Circuits. (United States)

    Park, Hong Geun; Carmel, Jason B


    Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain- and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

  1. Clinical study on orofacial photonic hydration using phototherapy and biomaterials (United States)

    Lizarelli, Rosane F. Z.; Grandi, Natália D. P.; Florez, Fernando L. E.; Grecco, Clovis; Lopes, Luciana A.


    Skin hydration is important to prevent aging and dysfunction of orofacial system. Nowadays, it is known that cutaneous system is linked to muscle system, then every dentist need to treat healthy facial skin, as lips, keeping orofacial functions healthy. Thirty-two patients were treated using laser and led therapy single or associated to biomaterials (dermo-cosmetics) searching for the best protocol to promote skin hydration. Using a peace of equipment to measure electric impedance, percentage of water and oil from skin, before and after different treatments were analyzed. Statistic tests using 5% and 0.1% of significance were applied and results showed that light could improve hydration of epidermis layer of facial skin. Considering just light effect, using infrared laser followed by blue led system is more effective to hydration than just blue led system application. Considering dermo-cosmetic and light, the association between both presented the best result.

  2. Double site-bond percolation model for biomaterial implants

    CERN Document Server

    Mely, H


    We present a double site-bond percolation model to account, on the one hand, for the vascularization and/or resorption of biomaterial implant in bones and, on the other hand, for its mechanical continuity. The transformation of the implant into osseous material, and the dynamical formation/destruction of this osseous material is accounted for by creation and destruction of links and sites in two, entangled, networks. We identify the relevant parameters to describe the implant and its evolution, and separate their biological or chemical origin from their physical one. We classify the various phenomena in the two regimes, percolating or non-percolating, of the networks. We present first numerical results in two dimensions.

  3. Various approaches to modify biomaterial surfaces for improving hemocompatibility. (United States)

    Mao, Chun; Qiu, Yongzhi; Sang, Haibo; Mei, Hua; Zhu, Aiping; Shen, Jian; Lin, Sicong


    In this paper, the mechanism of thrombus formation on the surface of polymeric materials and the various approaches of modifying biomaterial surfaces to improve their hemocompatibility are reviewed. Moreover, the blood compatibility of the cellulose membrane grafted with O-butyrylchitosan (OBCS) by using a radiation grafting technique was studied. Surface analysis of grafted cellulose membrane was verified by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and electron spectroscopy for chemical analysis (ESCA), which confirmed that OBCS was successfully grafted onto the cellulose membrane surfaces. Blood compatibility of the grafted cellulose membranes was evaluated by platelet rich plasma (PRP) contacting experiments and protein adsorption experiments using blank cellulose membranes as the control. The blood compatibility of OBCS grafted cellulose membranes is better than that of blank cellulose membranes. These results suggest that the photocrosslinkable chitosan developed here has the potential of serving in blood-contacting applications in medical use.

  4. Regulation of UHMWPE biomaterials in total hip arthroplasty. (United States)

    Kasser, Michael J


    This manuscript provides a brief history of the development of ultrahigh molecular weight polyethylene (UHWMPE) biomaterials and how the U.S. Food and Drug Administration (FDA) regulates medical devices. The flowchart used to decide whether a device is medium or high risk, known as the 510(k) flowchart, is illustrated by taking several examples through the flowchart. In order to demonstrate how changes to UHWMPE material used in the acetabular liners of total hips have been regulated, two major modifications to UHMWPE, highly crosslinked polyethylene and Vitamin E polyethylene, are taken through the flowchart. This manuscript describes the testing that has been provided to demonstrate safety and effectiveness of these modifications, as well as an explanation why the testing was supplied to the FDA.

  5. Gelatin Functionalization of Biomaterial Surfaces: Strategies for Immobilization and Visualization

    Directory of Open Access Journals (Sweden)

    Peter Dubruel


    Full Text Available In the present work, the immobilization of gelatin as biopolymer on two types of implantable biomaterials, polyimide and titanium, was compared. Both materials are known for their biocompatibility while lacking cell-interactive behavior. For both materials, a pre-functionalization step was required to enable gelatin immobilization. For the polyimide foils, a reactive succinimidyl ester was introduced first on the surface, followed by covalent grafting of gelatin. For the titanium material, methacrylate groups were first introduced on the Ti surface through a silanization reaction. The applied functionalities enabled the subsequent immobilization of methacrylamide modified gelatin. Both surface modified materials were characterized in depth using atomic force microscopy, static contact angle measurements, confocal fluorescence microscopy, attenuated total reflection infrared spectroscopy and X-ray photo-electron spectroscopy. The results indicated that the strategies elaborated for both material classes are suitable to apply stable gelatin coatings. Interestingly, depending on the material class studied, not all surface analysis techniques are applicable.

  6. Advances in Porous Biomaterials for Dental and Orthopaedic Applications

    Directory of Open Access Journals (Sweden)

    Arndt F. Schilling


    Full Text Available The connective hard tissues bone and teeth are highly porous on a micrometer scale, but show high values of compression strength at a relatively low weight. The fabrication of porous materials has been actively researched and different processes have been developed that vary in preparation complexity and also in the type of porous material that they produce. Methodologies are available for determination of pore properties. The purpose of the paper is to give an overview of these methods, the role of porosity in natural porous materials and the effect of pore properties on the living tissues. The minimum pore size required to allow the ingrowth of mineralized tissue seems to be in the order of 50 µm: larger pore sizes seem to improve speed and depth of penetration of mineralized tissues into the biomaterial, but on the other hand impair the mechanical properties. The optimal pore size is therefore dependent on the application and the used material.

  7. Gold nanoparticle-coated biomaterial as SERS micro-probes

    Indian Academy of Sciences (India)

    G V Pavan Kumar


    We report for the first time, on the utility of plant-based biomaterial as enhanced-Raman scattering probes. The bio-substrate used in this study are commonly found in plant extracts, and are cost-effective, mechanically robust, flexible and easily transportable. The probe was fabricated by coating the plant extract with gold nanoparticles and characterized. By employing a ‘single-touch contact’ method, we reveal the ability of these probes to detect routinely used Raman markers such as 2-napthalenethiol and rhodamine B, at nano-molar concentrations, in dry and liquid forms, respectively. Reproducibility of the signals with variation <5%, and the ability to detect biomolecules are demonstrated herein. We envision these bio-probes as potential candidates for enhanced Raman sensing in chemical, environmental, and archaeological applications. By further engineering the shape, morphology, and surface chemistry of these micro-probes, we foresee their utility as miniaturized, natural SERS substrates.

  8. Chitosan and fish collagen as biomaterials for regenerative medicine. (United States)

    Hayashi, Yoshihiko; Yamada, Shizuka; Yanagi Guchi, Kajiro; Koyama, Zenya; Ikeda, Takeshi


    This chapter focuses and reviews on the characteristics and biomedical application of chitosan and collagen from marine products and advantages and disadvantages of regeneration medicine. The understanding of the production processes of chitosan and collagen and the conformation of these biomaterials are indispensable for promoting the theoretical and practical availability. The initial inflammatory reactions associated with chitosan application to hard and soft tissues need to be controlled before it can be considered for clinical application as scaffold. Further, as chitosan takes too long for biodegradation in vivo, generally it is not suitable for the scaffold for degenerative medicine in especially dental pulp tissue. The collagen extract from the scales of tropical fish has been reported to have a degeneration temperature of 35°C. The properties of biocompatibility and biodegradation of fish atelocollagen are suitable for the scaffold in regenerative medicine.

  9. Soft X-ray emission studies of biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Kurmaev, E.Z. E-mail:; Werner, J.P.; Moewes, A.; Chiuzbaian, S.; Bach, M.; Ching, W.-Y.; Motozaki, W.; Otsuka, T.; Matsuya, S.; Endo, K.; Neumann, M


    Soft X-ray fluorescence measurements are used to characterize three groups of biomaterials: Vitamin B{sub 12} and derivatives, antioxidants (aspirin and paracetamol), and human teeth. We show that the chemical bonding in Vitamin B{sub 12} is characterized by the strong Co-C bond and the relatively weak Co-N bond. The Co-C bond in cyanocobalamin is found to be stronger than that of methylcobalamin leading to their different biological activity. The chemical bonding of paracetamol and aspirin is characterized by the formation of oxygen lone-pair {pi}-orbitals, which can neutralize free radicals and therefore be related to antioxidant activity of these compounds. Carbon K{alpha} emission spectra of a caries lesion suggest that the CaCO{sub 3} like phase exists in sound enamel and that a selective loss of carbonate occurs during the early stages of a caries attack.

  10. Behavioural and biomaterial coevolution in spider orb webs. (United States)

    Sensenig, A; Agnarsson, I; Blackledge, T A


    Mechanical performance of biological structures, such as tendons, byssal threads, muscles, and spider webs, is determined by a complex interplay between material quality (intrinsic material properties, larger scale morphology) and proximate behaviour. Spider orb webs are a system in which fibrous biomaterials--silks--are arranged in a complex design resulting from stereotypical behavioural patterns, to produce effective energy absorbing traps for flying prey. Orb webs show an impressive range of designs, some effective at capturing tiny insects such as midges, others that can occasionally stop even small birds. Here, we test whether material quality and behaviour (web design) co-evolve to fine-tune web function. We quantify the intrinsic material properties of the sticky capture silk and radial support threads, as well as their architectural arrangement in webs, across diverse species of orb-weaving spiders to estimate the maximum potential performance of orb webs as energy absorbing traps. We find a dominant pattern of material and behavioural coevolution where evolutionary shifts to larger body sizes, a common result of fecundity selection in spiders, is repeatedly accompanied by improved web performance because of changes in both silk material and web spinning behaviours. Large spiders produce silk with improved material properties, and also use more silk, to make webs with superior stopping potential. After controlling for spider size, spiders spinning higher quality silk used it more sparsely in webs. This implies that improvements in silk quality enable 'sparser' architectural designs, or alternatively that spiders spinning lower quality silk compensate architecturally for the inferior material quality of their silk. In summary, spider silk material properties are fine-tuned to the architectures of webs across millions of years of diversification, a coevolutionary pattern not yet clearly demonstrated for other important biomaterials such as tendon, mollusc

  11. Fatigue behavior of porous biomaterials manufactured using selective laser melting. (United States)

    Yavari, S Amin; Wauthle, R; van der Stok, J; Riemslag, A C; Janssen, M; Mulier, M; Kruth, J P; Schrooten, J; Weinans, H; Zadpoor, A A


    Porous titanium alloys are considered promising bone-mimicking biomaterials. Additive manufacturing techniques such as selective laser melting allow for manufacturing of porous titanium structures with a precise design of micro-architecture. The mechanical properties of selective laser melted porous titanium alloys with different designs of micro-architecture have been already studied and are shown to be in the range of mechanical properties of bone. However, the fatigue behavior of this biomaterial is not yet well understood. We studied the fatigue behavior of porous structures made of Ti6Al4V ELI powder using selective laser melting. Four different porous structures were manufactured with porosities between 68 and 84% and the fatigue S-N curves of these four porous structures were determined. The three-stage mechanism of fatigue failure of these porous structures is described and studied in detail. It was found that the absolute S-N curves of these four porous structures are very different. In general, given the same absolute stress level, the fatigue life is much shorter for more porous structures. However, the normalized fatigue S-N curves of these four structures were found to be very similar. A power law was fitted to all data points of the normalized S-N curves. It is shown that the measured data points conform to the fitted power law very well, R(2)=0.94. This power law may therefore help in estimating the fatigue life of porous structures for which no fatigue test data is available. It is also observed that the normalized endurance limit of all tested porous structures (<0.2) is lower than that of corresponding solid material (c.a. 0.4).

  12. Gloss measurements and rugometric inspection in dental biomaterials (United States)

    Fernández-Oliveras, Alicia; Costa, Manuel F. M.; Yebra, Ana; Rubiño, Manuel; Pérez, María. M.


    In dental applications, optimizing appearance is desirable and increasingly demanded by patients. The specular gloss is among the major appearance properties of dental biomaterials, and its relationship with surface roughness has been reported. Roughness and gloss are key surface aspects that complement each other. We have experimentally analyzed the specular gloss and surface roughness of two different types of dental-resin composites and pre-sintered and sintered zirconia ceramics. We have studied two shades of both composite types and two sintered zirconia ceramics: colored and uncolored. Moreover, a surface treatment was applied to one specimen of each dental resin. Gloss measurements were performed with a standardized reflectometer and the corresponding gloss percentages were calculated. All the samples were submitted to rugometric non-invasive inspection with the MICROTOP.06.MFC laser microtopographer in order to determine meaningful statistical parameters such as the average roughness (Ra) and the root-mean-square deviation (Rq). For a comparison of the different biomaterials, the uncertainties associated to the measure of the surface gloss and roughness were also determined. The differences between the two shades of both kinds of composites proved significant in the case of the roughness parameters but not for the specular gloss. The surface treatment applied to the dental-resin composites increased the average roughness but the changes in the specular gloss were significant only for the A2 enamel nano-composite. For the zirconia ceramic the sintered process resulted in an increase in the surface roughness with a decrease of the specular gloss, corroborating that the relationship between the gloss and the roughness shows the expected behavior.

  13. [Structure, use, and risks of biomaterial repositories of embryonal tumors]. (United States)

    Ernestus, K; Pietsch, T; Gessler, M; Simon, T; Hero, B; Berthold, F


    Availability of statistically sufficient numbers of tumor samples and other biomaterials in high quality together with corresponding clinical data is crucial for biomedical research. Tumor repositories from individual scientists are mostly not sufficient to satisfy these criteria, especially since pediatric tumors are rare. In 2000 three centralized tumor repositories (neuroblastoma in Cologne, nephroblastoma in Würzburg, hepatoblastoma, brain tumors in Bonn) have been established by the "German Competence Net Pediatric Oncology und Hematology". The aim was to collect biomaterial including tumor samples, normal tissue, and blood in high quality for research and diagnostic purposes at a central institution. Informed consent of the parents or patients is a prerequisite for scientific use of the samples and is requested by the therapy trial. The samples are collected according to accepted standards and shipped in the specially designed Tumorbox. The tumor repository organizes the distribution of the samples to the cooperating diagnostic laboratories. The number of collected tumor samples has increased over the years. In 2000, samples from 200 patients were collected while the patient number increased to 321 in 2005. Over the years the tumor repositories collected more than 7,150 samples (fresh frozen tumor, fresh frozen normal tissue, and blood). Through links with clinical trial databases the samples can be connected with clinical data. 12 of 14 applications for tumor material to be used in specific scientific projects have been approved by an independent supervisory board. The establishment of central tumor repositories represents a major step for biomedical research activities and quality control in pediatric oncology.

  14. Neural Network Applications

    NARCIS (Netherlands)

    Vonk, E.; Jain, L.C.; Veelenturf, L.P.J.


    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  15. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials. (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L


    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4(+) T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment.

  16. Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures (United States)

    Knight, V. Bleu


    Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA) cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

  17. Hydrogel scaffolds promote neural gene expression and structural reorganization in human astrocyte cultures

    Directory of Open Access Journals (Sweden)

    V. Bleu Knight


    Full Text Available Biomaterial scaffolds have the potential to enhance neuronal development and regeneration. Understanding the genetic responses of astrocytes and neurons to biomaterials could facilitate the development of synthetic environments that enable the specification of neural tissue organization with engineered scaffolds. In this study, we used high throughput transcriptomic and imaging methods to determine the impact of a hydrogel, PuraMatrix™, on human glial cells in vitro. Parallel studies were undertaken with cells grown in a monolayer environment on tissue culture polystyrene. When the Normal Human Astrocyte (NHA cell line is grown in a hydrogel matrix environment, the glial cells adopt a structural organization that resembles that of neuronal-glial cocultures, where neurons form clusters that are distinct from the surrounding glia. Statistical analysis of next generation RNA sequencing data uncovered a set of genes that are differentially expressed in the monolayer and matrix hydrogel environments. Functional analysis demonstrated that hydrogel-upregulated genes can be grouped into three broad categories: neuronal differentiation and/or neural plasticity, response to neural insult, and sensory perception. Our results demonstrate that hydrogel biomaterials have the potential to transform human glial cell identity, and may have applications in the repair of damaged brain tissue.

  18. How smart do biomaterials need to be? A translational science and clinical point of view. (United States)

    Holzapfel, Boris Michael; Reichert, Johannes Christian; Schantz, Jan-Thorsten; Gbureck, Uwe; Rackwitz, Lars; Nöth, Ulrich; Jakob, Franz; Rudert, Maximilian; Groll, Jürgen; Hutmacher, Dietmar Werner


    Over the last 4 decades innovations in biomaterials and medical technology have had a sustainable impact on the development of biopolymers, titanium/stainless steel and ceramics utilized in medical devices and implants. This progress was primarily driven by issues of biocompatibility and demands for enhanced mechanical performance of permanent and non-permanent implants as well as medical devices and artificial organs. In the 21st century, the biomaterials community aims to develop advanced medical devices and implants, to establish techniques to meet these requirements, and to facilitate the treatment of older as well as younger patient cohorts. The major advances in the last 10 years from a cellular and molecular knowledge point of view provided the scientific foundation for the development of third-generation biomaterials. With the introduction of new concepts in molecular biology in the 2000s and specifically advances in genomics and proteomics, a differentiated understanding of biocompatibility slowly evolved. These cell biological discoveries significantly affected the way of biomaterials design and use. At the same time both clinical demands and patient expectations continued to grow. Therefore, the development of cutting-edge treatment strategies that alleviate or at least delay the need of implants could open up new vistas. This represents the main challenge for the biomaterials community in the 21st century. As a result, the present decade has seen the emergence of the fourth generation of biomaterials, the so-called smart or biomimetic materials. A key challenge in designing smart biomaterials is to capture the degree of complexity needed to mimic the extracellular matrix (ECM) of natural tissue. We are still a long way from recreating the molecular architecture of the ECM one to one and the dynamic mechanisms by which information is revealed in the ECM proteins in response to challenges within the host environment. This special issue on smart

  19. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface. (United States)

    Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B


    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.

  20. Electric Field-Mediated Processing of Biomaterials: Toward Nanostructured Biomimetic Systems. Appendix 3 (United States)

    Bowlin, Gary L.; Simpson, David G.; Lam, Philippe; Wnek, Gary E.


    Significant opportunities exist for the processing of synthetic and biological polymers using electric fields ('electroprocessing'). We review casting of multi-component films and the spinning of fibers in electric fields, and indicate opportunities for the creation of smart polymer systems using these approaches. Applications include 2-D substrates for cell growth and diagnostics, scaffolds for tissue engineering and repair, and electromechanically active biosystems.

  1. Filler particles used in dental biomaterials induce production and release of inflammatory mediators in vitro. (United States)

    Ansteinsson, Vibeke E; Samuelsen, Jan Tore; Dahl, Jon E


    Although dental composites are in extensive use today, little is known about the biological effects of the filler particles. As composite materials are gradually broken down in the aggressive environment of the oral cavity, the filler particles may leak and induce toxic effects on the surrounding tissue and cells. The aim of this study was to elucidate possible adverse biological effects of commonly used dental filler particles; bariumaluminiumsilica (BaAlSi) and bariumaluminiumfluorosilica (BaAlFSi) with mean size of 1 microm. BEAS-2B cells were used as a model system. Particle morphology, mean particle size in solution, and particle surface charge were determined by scanning electron microscopy and Malvern zetasizer technology, respectively. Enzyme-linked immunosorbent assay was used to detect secretion of cytokine and chemokine (IL-8 and IL-6) and quantitative PCR for detection of gene activity. Both types of particle increased the release of IL-6 and IL-8 in a dose-dependent manner. BaAlFSi particles induced a more marked IL-8 response compared to BaAlSi particles, whereas no significant difference was observed for the IL-6 response. Mechanistic studies using specific inhibitors and activators indicated that cyclic AMP-dependent protein kinase A is partly involved in the observed IL-8 response. In conclusion, we consider dental filler particles to have potential to induce adverse biological response in cell cultures.

  2. Folate receptor alpha is necessary for neural plate cell apical constriction during Xenopus neural tube formation. (United States)

    Balashova, Olga A; Visina, Olesya; Borodinsky, Laura N


    Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor-α (FRα) impairs neural tube formation and leads to NTDs. FRα knockdown in neural plate cells only is necessary and sufficient to induce NTDs. FRα-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model for folate receptor interacting with cell adhesion molecules, thus regulating apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism may unveil novel cellular and molecular events mediated by folate and lead to new means for preventing NTDs.

  3. Coagulation on biomaterials in flowing blood: some theoretical considerations. (United States)

    Basmadjian, D; Sefton, M V; Baldwin, S A


    Are truly inert biomaterials feasible? Recent mathematical models of coagulation which are reviewed here suggest that such materials are impossible. This conclusion, which is certainly consistent with our collective experimental evidence, arises from the calculation that conversion of Factor XI to XIa never drops to zero even at the highest flow rates and with virtually no Factor XIIa bound to a surface. Residual amounts of XIa are still formed which can in principle kick-off the coagulation cascade. Furthermore, if the flow rates and corresponding mass transfer coefficients are low and in spite of these near-vanishing levels of the initiating coagulants, the surprising result is that substantial amounts of thrombin are produced. On the contrary, under slightly higher flow conditions, there can be more substantial levels of initiating coagulants, yet paradoxically thrombin production is near zero. This article presents a theoretical understanding of the events which take place during the interaction of biomaterials with flowing blood. We follow these events from the time of first contact to the final production of thrombin. The effect of flow and surface activity on the contact phase reactions is examined in detail and the two are found to be intertwined. The common pathway is also examined and here the main feature is the existence of three flow dependent regions which produce either high or very low levels of thrombin, as well as multiple thrombin steady states. In a final analysis we link the two segments of the cascade and consider the events which result. In addition, we note that multiple steady states arise only in the presence of two (thrombin) feedback loops. Single loops or the bare cascade will produce only single steady states. With some imagination one can attribute to the feedback loops the role of providing the cascade with a mechanism to produce high thrombin levels in case of acute need (e.g. bleeding) or to allow levels to subside to 'stand

  4. Analysis of the strengthening and toughening of a biomaterial interface

    Institute of Scientific and Technical Information of China (English)

    SONG; Fan


    [1]Currey, J. D., Mechanical properties of mother of pearl in tension, Proc. R. Soc. Lond. B, 1977, 196: 443—463.[2]Jackson, A. P., Vincent, J. F. V., Turner, R. M., The mechanical design of nacre, Proc. R. Soc. Lond. B., 1988, 234: 415—440.[3]Wang, R. Z., Wen, H. B., Cui, F. Z. et al., Observations of damage morphologies in nacre during deformation and fracture, J. Mater. Sci., 1995, 30: 2299—2304.[4]Smith, B. L., Schaffer, T. E., Viani, M. et al., Molecular mechanistic origin of the toughness of natural adhesives, fibres and composites, Nature, 1999, 399: 761—763.[5]Addadi, L., Weiner, S., A pavement of pearl, Nature, 1997, 389: 912—915.[6]Schaffer,T. E., Ionescu-Zantti, C., Fritz, M. et al., Does abalone nacre form by heteroepiaxial nucleation or by growth through mineral bridges? Chem. Mater., 1997, 9: 1731—1740.[7]Vincent, J. F. V., Structural Biomaterials, New York; The Macmillan Press Ltd, 1982.[8]Song, F., Bai, Y. L., Effects of mineral bridges on the mechanical properties of nacre, Acta Mechanica Solida Sinica (in Chinese), 2000, 21(Special Issue): 171—176.[9]Szuromi, P., Microstructural engineering of materials, Science, 1997, 277: 1183—1183.[10]Heuer, A. H., Fink, D. J., Laraia, J. L. et al., Innovative materials processing strategies: a biomimetic approach, Science, 1992, 255: 1098—1105.[11]Stupp, S. I., Braun, P. V., Molecular manipulation of microstructure: biomaterials, ceramics, and semiconductors, Science, 1997, 277: 1242—1248.[12]Watabe, N., Crystal growth of calcium carbonate in the invertebrates, Prog. Crystal Growth Charact., 1981, 4: 99—147.[13]Clegg, W. J., Kendall, K., Alford, N. M. et al., A simple way to make tough ceramics, Nature, 1990, 347: 455—457.[14]Jackson, A. P., Vincent, J. F. V., Briggs, D. et al., Application of surface analytical techniques to the study fracture surface of mother-of pearl, J. Mater. Science Letters, 1986, 5: 975—980.[15

  5. Finite Element Simulation of the Mechanical Properties of Mineralized Biomaterials (United States)

    Yuan, Fang

    Mineralized biomaterials are natural composite materials with both biomineral and biopolymer phases. They have attracted intense attention in the past decades, due to their outstanding mechanical properties and great potential as future materials. Such exceptional properties are believed to be attributed to their complex structures. Therefore, two different mineralized biomaterials (bone and sea urchin spine) were studied mainly by the finite element method and their structure-mechanical properties relationships were investigated. The research on bone was performed with a bottom-up approach. We focused on the nanoscale level structure-properties relationship first: the models of mineralized collagen fibril, consisting of hydroxyapatite platelets aligned within a collagen matrix, were created and the importance of the parameters defining its structure and constituent properties was evaluated. With the elastic model well established, the long-term mechanical behavior at nanoscale level was studied. The viscoelastic properties of undamaged collagen phase were deduced from low-irradiation-dosage creep measurements, then different damage scenarios were evaluated to explain the evolution of phase strains with larger irradiation dosage. The higher level structure-properties relationship of bone was simulated by two different approaches: 1) Assuming the macroscopic composite strain was comparable to nanoscale fibrillar strain, then based on nanoscale model, the macroscopic distributions of nanoscale phase strains were investigated; 2) Considering the structural complexity of bone at several length scales, the effective properties from lower scales were applied as the input properties at higher scales, and the elastic properties at each level were investigated. The computational results were validated by experimental data obtained by synchrotron X-ray diffraction and show the mechanical properties of bone are greatly influenced by its structure. The research on sea urchin

  6. Tissue response to a new type of biomaterial implanted subcutaneously in rats

    DEFF Research Database (Denmark)

    Boennelycke, Marie; Christensen, Lise; Nielsen, Lene Feldskov


    A new type of resorbable biomaterial intended for pelvic reconstruction was tested with respect to tissue regeneration and biocompatibility in rats. The biomaterial consisted of methoxypolyethyleneglycol-poly (lactic-co-glycolic acid) (MPEG-PLGA). Implants were pure, enriched with extra-cellular ......A new type of resorbable biomaterial intended for pelvic reconstruction was tested with respect to tissue regeneration and biocompatibility in rats. The biomaterial consisted of methoxypolyethyleneglycol-poly (lactic-co-glycolic acid) (MPEG-PLGA). Implants were pure, enriched with extra...... of tissue regeneration. Thus, it is hardly a candidate per se in reinforcement of pelvic reconstruction, but it could have a future role as carrier for stem cells....

  7. Biomaterials for Pelvic Floor Reconstructive Surgery: How Can We Do Better?

    Directory of Open Access Journals (Sweden)

    Giulia Gigliobianco


    Full Text Available Stress urinary incontinence (SUI and pelvic organ prolapse (POP are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes.

  8. Treatment and prevention of Staphylococcus epidermidis experimental biomaterial-associated infection by bactericidal peptide 2

    NARCIS (Netherlands)

    P.H.S. Kwakman; A.A.T. Velde; C.M.J.E. Vandenbroucke-Grauls; S.J.H. van Deventer; S.A.J. Zaat


    Biomaterial-associated infections (BAI) are the major cause of failure of indwelling medical devices and are predominantly caused by staphylococci, especially Staphylococcus epidermidis. We investigated the in vitro microbicidal activity of the synthetic antimicrobial peptide bactericidal peptide 2

  9. Design, clinical translation and immunological response of biomaterials in regenerative medicine (United States)

    Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.


    The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure-function relationships of cell-material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

  10. The usage of three-dimensional nanostructurized biomaterials in experimental and clinical oncology

    Institute of Scientific and Technical Information of China (English)


    @@ The usage of biotransplants for substitution of tissue defects (in particular in reconstructive surgery in oncology) require both he suitable cell cultures and different biomaterials with definite and regulate properties.

  11. The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior (United States)

    Ordikhani, Faride; Kim, Yonghyun; Zustiak, Silviya P.


    The theory of cancer stem cells (CSCs) and their role in cancer metastasis, tumorigenicity and resistance to therapy is slowly shifting the emphasis on the search for cancer cure: more evidence is surfacing that a successful therapy should be geared against this rare cancer cell population. Unfortunately, CSCs are difficult to culture in vitro which severely limits the progress of CSC research. This review gives a brief overview of CSCs and their microenvironment, with particular focus on studies that used in vitro biomaterial-based models and biomaterial/CSC interfaces for the enrichment of CSCs. Biomaterial properties relevant to CSC behaviors are also addressed. While the discussed research field is still in its infancy, it appears that in vitro cancer models that include a biomaterial can support CSC enrichment and this has proved indispensable to the study of their biology as well as the development of novel cancer therapies.

  12. The usage of three-dimensional nanostructurized biomaterials in experimental and clinical oncology

    Institute of Scientific and Technical Information of China (English)

    Sergeeva; N.; S.; Reshetov; I.; V.; Sviridova; I.; K.; Kirsanova; V.; A.; Achmedova; S.; A.; Barinov; S.; M.; Komlev; V.; S.; Samoylovich; M.; I.; Belyanin; A.; F.; Kleshcheva; S.; M.; Elinson; V.; M.


    The usage of biotransplants for substitution of tissue defects (in particular in reconstructive surgery in oncology) require both he suitable cell cultures and different biomaterials with definite and regulate properties.……

  13. Bone grafting with granular biomaterial in segmental maxillary osteotomy: A case report

    Directory of Open Access Journals (Sweden)

    Orion Luiz Haas Junior


    Conclusion: This is the first report of bone grafting with a granular biomaterial in segmental maxillary osteotomy. Successful formation of new bone with density greater than that of the surrounding tissue was achieved, preventing pseudarthrosis and postoperative instability.

  14. Apoptotic gene expression in the neural tube during early human embryonic development

    Institute of Scientific and Technical Information of China (English)

    Guifang Chen; Tiandong Li; Peipei Ding; Ping Yang; Xiao Zhang


    Neural tube development comprises neural induction,neural epithelial cell proliferation,and apoptosis,as well as migration of nerve cells.Too much or too little apoptosis leads to abnormal nervous system development.The present study analyzed expression and distribution of apoptotic-related factors,including Fas,FasL,and caspase-3,during human embryonic neural tube development.Experimental results showed that increased caspase-3 expression promoted neural apoptosis via a mitochondriai-mediated intrinsic pathway at 4 weeks during early human embryonic neural tube development.Subsequently,Fas and FasL expression increased during embryonic development.The results suggest that neural cells influence neural apoptosis through synergistic effects of extrinsic pathways.Therefore,neural apoptosis during the early period of neural tube development in the human embryo might be regulated by the death receptor induced apoptotic extrinsic pathways.

  15. Osteoblast Behaviour on Injectable Biomaterials Intended for Augmentation of Vertebral Compression Fractures


    Ramstedt, Sandra


    Biomaterials used for stabilization of compressed vertebraes due to osteoporosis, have mainly been based on resin materials, like PMMA (polymethyl methacrylate), but have recently expanded to consist of injectable ceramics, such as calcium-aluminate. In this in vitro study human osteoblast-like cells, MG-63, were cultured on three different injectable biomaterials based on: Ca-aluminate, Bis-GMA (bisphenol A-glycidylmethacrylate) and PMMA, to investigate the cellular response elicited by thes...

  16. Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Sally A. Moody


    Full Text Available The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

  17. Investigation of Transport Properties of a New Biomaterials - GUM Mangosteen (United States)

    Pradhan, Sourav S.; Sarkar, A.


    Biomaterial has occupied leading position in material science for various scientific and technological applications. This present work is carried out over a natural gum extracted from raw fruit of Mangosteen, an east Indian tree (Gercinia Mangostana) following extraction and purification process. Solid specimen of the said gum is developed following sol-gel like process. AC and DC electrical analysis on the dried solid specimen of the gum were carried out and showed high electrical conduction with σ ~ 1 E-03 S/cm, of which ionic and electronic contributions are 70% and 30% respectively. Analysis shows that origin of high electrical conductivity is due to presence of substantial amount of organic acid unit in its polysaccharide background. In fact the observed σ is about 1000 times of that observed in gum Arabica. Optical absorption of this new bio- materials are also studied using UV-VIS analysis. The results show its high absorption co-efficient in UV and blue part of analysed range. A complete electrical characterization of the material have been made. It has also been observed that the electronic conduction can be enhanced to 70% of the total electrical conductivity by forming complex with Iodine and organic (Citric) acid from Lemon fruit. This high potential material is being studied for development of electronic device application.

  18. Esthetic prevention with soft tissue and biomaterial grafts

    Directory of Open Access Journals (Sweden)

    Rogério Margonar

    Full Text Available Gingival recessions are periodontal defects that may need the association of surgical techniques in order to be successfully treated. The absence of treatment of these defects may lead to local esthetics being compromised, patient dissatisfaction, and reduced time and duration of treatment. When dealing with dental implants, the esthetic condition is no different, with the aggravating factor that the lack of this protective tissue may accelerate vestibular bone loss and lead to loss of the implant. The clinical case presented report the performance of a conjunctive tissue grafting technique, associated with vestibular filling with biomaterial, to prevent a gingival recession in an immediate implant with immediate loading. The aim of the procedure was to prevent gingival recession, which would lead to a severe esthetic defect, and also to reinforce the vestibular bone wall. After three years of follow-up of the case, it was possible to conclude that the association of thetechniques had predictable and satisfactory results for preventing periimplant gingival recession.

  19. Atmospheric Microplasma Application for Surface Modification of Biomaterials (United States)

    Shimizu, Kazuo; Fukunaga, Hodaka; Tatematsu, Shigeki; Blajan, Marius


    Atmospheric microplasma has been intensively studied for applications in various fields, since in this technology the generated field is only 1 kV (approx) under atmospheric pressure and a dielectric barrier discharge gap of 10 to 100 µm. A low discharge voltage atmospheric plasma process is an economical and effective solution for various applications such as indoor air control including sterilization, odor removal, and surface treatment, and would be suitable for medical applications in the field of plasma life sciences. In this paper, we present the application of microplasma for the surface treatment of materials used in medical fields. Moreover, a biomaterial composed of L-lactic acid is used in experiments, which can be biodecomposed in the human body after medical operations. The surface modification process was carried out with active species generated between the microplasma electrodes, which were observed by emission spectrometry. Microplasma treatment of a polymer sheet using Ar as the process gas decreased the contact angle of a water droplet at the surface of the polymer from 78.3 to 45.6° in 10 s, indicating improved surface adhesive characteristics.

  20. Natural polysaccharides as active biomaterials in nanostructured films for sensing. (United States)

    Eiras, Carla; Santos, Amanda C; Zampa, Maysa F; de Brito, Ana Cristina Facundo; Leopoldo Constantino, Carlos J; Zucolotto, Valtencir; dos Santos, José R


    The search for natural, biocompatible and degradable materials amenable to be used in biomedical/analytical applications has attracted attention, either from the environmental or medical point of view. Examples are the polysaccharides extracted from natural gums, which have found applications in the food and pharmaceutical industries as stabilizers or thickening agent. In a previous paper, however, it was shown that a Brazilian natural gum, chicha (Sterculia striata), is suitable for application as building block for nanostructured film fabrication in conjunction with phthalocyanines. The films displayed electroactivity and could be used in sensing. In the present paper, we introduce the use of two different natural gums, viz., angico (Anadenanthera colubrina) and caraia (Sterculia urens), as active biomaterials to be used to modification layers, in the form of nanostructured thin films, including the study of dopamine detection. The multilayer films were assembled in conjunction with nickel tetrasulfonated phthalocyanines (NiTsPC) and displayed good chemical and electrochemical stability, allowing their use as transducer elements in sensors for detection of specific neurotransmitters. It is suggested here that nanoscale manipulation of new biodegradable natural polymers opens up a variety of new opportunities for the use of these materials in advanced biomedical and analytical devices.

  1. Stents: Biomechanics, Biomaterials, and Insights from Computational Modeling. (United States)

    Karanasiou, Georgia S; Papafaklis, Michail I; Conway, Claire; Michalis, Lampros K; Tzafriri, Rami; Edelman, Elazer R; Fotiadis, Dimitrios I


    Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity. Stent design variables and expansion properties are critical for vessel scaffolding. Drug-elution from stents, can help inhibit in-stent restenosis, but adds further complexity as drug release kinetics and coating formulations can dominate tissue responses. Biodegradable and bioabsorbable stents go one step further providing complete absorption over time governed by corrosion and erosion mechanisms. The advances in computing power and computational methods have enabled the application of numerical simulations and the in silico evaluation of the performance of stent devices made up of complex alloys and bioerodible materials in a range of dimensions and designs and with the capacity to retain and elute bioactive agents. This review presents the current knowledge on stent biomechanics, stent fatigue as well as drug release and mechanisms governing biodegradability focusing on the insights from computational modeling approaches.

  2. Alginate: A Versatile Biomaterial to Encapsulate Isolated Ovarian Follicles. (United States)

    Vanacker, Julie; Amorim, Christiani A


    In vitro culture of ovarian follicles isolated or enclosed in ovarian tissue fragments and grafting of isolated ovarian follicles represent a potential alternative to restore fertility in cancer patients who cannot undergo cryopreservation of embryos or oocytes or transplantation of frozen-thawed ovarian tissue. In this regard, respecting the three-dimensional (3D) architecture of isolated follicles is crucial to maintaining their proper follicular physiology. To this end, alginate hydrogel has been widely investigated using follicles from numerous animal species, yielding promising results. The goal of this review is therefore to provide an overview of alginate applications utilizing the biomaterial as a scaffold for 3D encapsulation of isolated ovarian follicles. Different methods of isolated follicle encapsulation in alginate are discussed in this review, as its use of 3D alginate culture systems as a tool for in vitro follicle analysis. Possible improvements of this matrix, namely modification with arginine-glycine-aspartic acid peptide or combination with fibrin, are also summarized. Encouraging results have been obtained in different animal models, and particularly with isolated follicles encapsulated in alginate matrices and grafted to mice. This summary is designed to guide the reader towards development of next-generation alginate scaffolds, with enhanced properties for follicle encapsulation.

  3. Adsorption of cadmium(II) on waste biomaterial. (United States)

    Baláž, M; Bujňáková, Z; Baláž, P; Zorkovská, A; Danková, Z; Briančin, J


    Significant increase of the adsorption ability of the eggshell biomaterial toward cadmium was observed upon milling, as is evidenced by the value of maximum monolayer adsorption capacity of 329mgg(-1), which is markedly higher than in the case of most "green" sorbents. The main driving force of the adsorption was proven to be the presence of aragonite phase as a consequence of phase transformation from calcite occurring during milling. Cadmium is adsorbed in a non-reversible way, as documented by different techniques (desorption tests, XRD and EDX measurements). The optimum pH for cadmium adsorption was 7. The adsorption process was accompanied by the increase of the value of specific surface area. The course of adsorption has been described by Langmuir, Freundlich and Dubinin-Radushkevich isotherms. The adsorption kinetics was evaluated using three models, among which the best correlation coefficients and the best normalized standard deviation values were achieved for the pseudo-second order model and the intraparticle diffusion model, respectively.

  4. Controlling fungal biofilms with functional drug delivery denture biomaterials. (United States)

    Wen, Jianchuan; Jiang, Fuguang; Yeh, Chih-Ko; Sun, Yuyu


    Candida-associated denture stomatitis (CADS), caused by colonization and biofilm-formation of Candida species on denture surfaces, is a significant clinical concern. We show here that modification of conventional denture materials with functional groups can significantly increase drug binding capacity and control drug release rate of the resulting denture materials for potentially managing CADS. In our approach, poly(methyl methacrylate) (PMMA)-based denture resins were surface grafted with three kinds of polymers, poly(1-vinyl-2-pyrrolidinone) (PNVP), poly(methacrylic acid) (PMAA), and poly(2-hydroxyethyl methacrylate) (PHEMA), through plasma-initiated grafting polymerization. With a grafting yield as low as 2 wt%, the three classes of new functionalized denture materials showed significantly higher drug binding capacities toward miconazole, a widely used antifungal drug, than the original PMMA denture resin control, leading to sustained drug release and potent biofilm-controlling effects against Candida. Among the three classes of functionalized denture materials, PNVP-grafted resin provided the highest miconazole binding capability and the most powerful antifungal and biofilm-controlling activities. Drug binding mechanisms were studied. These results demonstrated the importance of specific interactions between drug molecules and functional groups on biomaterials, shedding lights on future design of CADS-managing denture materials and other related devices for controlled drug delivery.

  5. Combustion synthesis and photoluminescence study of silicate biomaterials

    Indian Academy of Sciences (India)

    V B Bhatkar; N V Bhatkar


    Silicate based bioceramics are promising candidates as biomaterials for tissue engineering. The combustion synthesis method provides control on the morphology and particle size of the synthesized material. This paper discusses the combustion synthesis of akermanite (Ca2MgSi2O7 and Sr2MgSi2O7), which has been shown to have good in vitro and in vivo bioactivities by earlier studies. Both Ca2MgSi2O7 and Sr2MgSi2O7 have akermanite structure. Ca2MgSi2O7 and Sr2MgSi2O7 were prepared using urea and ammonium nitrate. The combustion synthesis using urea and ammonium nitrate was found to be cost effective and efficient method of synthesis. The photoluminescence study of Ca2MgSi2O7 : Eu2+ and Sr2MgSi2O7 :Eu2+ shows host specific intense emission of Eu2+.

  6. Role of polymeric biomaterials as wound healing agents. (United States)

    Agrawal, Priyanka; Soni, Sandeep; Mittal, Gaurav; Bhatnagar, Aseem


    In uncontrolled hemorrhage, the main cause of death on the battlefield and in accidents, half of the deaths are caused by severe blood loss. Polymeric biomaterials have great potential in the control of severe hemorrhage from trauma, which is the second leading cause of death in the civilian community following central nervous system injuries. The intent of this article is to provide a review on currently available biopolymers used as wound dressing agents and to describe their best use as it relates to the condition and type of the wound (acute, chronic, superficial, and full thickness) and the phases of the wound healing process. These biopolymers are beneficial in tissue engineering as scaffolds, hydrogels, and films. Different types of wound dressings based on biopolymers are available in the market, with various physical, chemical, and biological properties. The use of biopolymers as a hemostatic agent depends on its biocompatibility, biodegradability, nonimmunogenicity, and optimal mechanical property. This review summarizes different biopolymers, their physiological characters, and their use as wound healing agents along with biomedical applications.

  7. Biomaterial-Derived Calcium Carbonate Nanoparticles for Enteric Drug Delivery

    Directory of Open Access Journals (Sweden)

    Diane Render


    Full Text Available Oral drug delivery systems provide the most convenient, noninvasive, readily acceptable alternatives to parenteral systems. In the current work, eggshell-derived calcium carbonate (CaCO3 nanoparticles were used to develop enteric drug delivery system in the form of tablets. CaCO3 nanoparticles were manufactured using top-down ball-milling method and characterized by X-ray diffractometry (XRD and transmission electron microscopy (TEM and loaded with 5-fluorouracil as a model drug. Tablets with varying CaCO3 core and binder compositions were fabricated and coated with Eudragit S100 or Eudragit L100. Suitability for enteric delivery of the tablets was tested by oral administration to rabbits and radiography. Radiograph images showed that the tablet remained in the stomach of the rabbit for up to 3 hours. Further modifications of these biomaterial-derived nanoparticles and the coatings will enable manufacturing of stable formulations for slow or controlled release of pharmaceuticals for enteric delivery.

  8. Protein-surface interactions on stimuli-responsive polymeric biomaterials. (United States)

    Cross, Michael C; Toomey, Ryan G; Gallant, Nathan D


    Responsive surfaces: a review of the dependence of protein adsorption on the reversible volume phase transition in stimuli-responsive polymers. Specifically addressed are a widely studied subset: thermoresponsive polymers. Findings are also generalizable to other materials which undergo a similarly reversible volume phase transition. As of 2015, over 100,000 articles have been published on stimuli-responsive polymers and many more on protein-biomaterial interactions. Significantly, fewer than 100 of these have focused specifically on protein interactions with stimuli-responsive polymers. These report a clear trend of increased protein adsorption in the collapsed state compared to the swollen state. This control over protein interactions makes stimuli-responsive polymers highly useful in biomedical applications such as wound repair scaffolds, on-demand drug delivery, and antifouling surfaces. Outstanding questions are whether the protein adsorption is reversible with the volume phase transition and whether there is a time-dependence. A clear understanding of protein interactions with stimuli-responsive polymers will advance theoretical models, experimental results, and biomedical applications.

  9. Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

    Directory of Open Access Journals (Sweden)

    Subhamoy Das


    Full Text Available Wound healing is an intricate process that requires complex coordination between many cells and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care; the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds including excessive inflammation, ischemia, scarring and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or currently used in clinical practice.

  10. Use of electrospinning to construct biomaterials for peripheral nerve regeneration. (United States)

    Quan, Qi; Chang, Biao; Meng, Hao Ye; Liu, Ruo Xi; Wang, Yu; Lu, Shi Bi; Peng, Jiang; Zhao, Qing


    A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

  11. Preparation of hybrid biomaterials for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Vilma Conceição Costa


    Full Text Available Tissue engineering has evolved from the use of biomaterials for bone substitution that fulfill the clinical demands of biocompatibility, biodegradability, non-immunogeneity, structural strength and porosity. Porous scaffolds have been developed in many forms and materials, but few reached the need of adequate physical, biological and mechanical properties. In the present paper we report the preparation of hybrid porous polyvinyl alcohol (PVA/bioactive glass through the sol-gel route, using partially and fully hydrolyzed polyvinyl alcohol, and perform structural characterization. Hybrids containing PVA and bioactive glass with composition 58SiO2-33CaO-9P2O5 were synthesized by foaming a mixture of polymer solution and bioactive glass sol-gel precursor solution. Sol-gel solution was prepared from mixing tetraethoxysilane (TEOS, triethylphosphate (TEP, and calcium chloride as chemical precursors. The hybrid composites obtained after aging and drying at low temperature were chemically and morphologically characterized through infrared spectroscopy and scanning electron microscopy. The degree of hydrolysis of PVA, concentration of PVA solution and different PVA-bioglass composition ratios affect the synthesis procedure. Synthesis parameters must be very well combined in order to allow foaming and gelation. The hybrid scaffolds obtained exhibited macroporous structure with pore size varying from 50 to 600 µm.

  12. A Tubular Biomaterial Construct Exhibiting a Negative Poisson's Ratio.

    Directory of Open Access Journals (Sweden)

    Jin Woo Lee

    Full Text Available Developing functional small-diameter vascular grafts is an important objective in tissue engineering research. In this study, we address the problem of compliance mismatch by designing and developing a 3D tubular construct that has a negative Poisson's ratio νxy (NPR. NPR constructs have the unique ability to expand transversely when pulled axially, thereby resulting in a highly-compliant tubular construct. In this work, we used projection stereolithography to 3D-print a planar NPR sheet composed of photosensitive poly(ethylene glycol diacrylate biomaterial. We used a step-lithography exposure and a stitch process to scale up the projection printing process, and used the cut-missing rib unit design to develop a centimeter-scale NPR sheet, which was rolled up to form a tubular construct. The constructs had Poisson's ratios of -0.6 ≤ νxy ≤ -0.1. The NPR construct also supports higher cellular adhesion than does the construct that has positive νxy. Our NPR design offers a significant advance in the development of highly-compliant vascular grafts.

  13. Binding Quantum Dots to Silk Biomaterials for Optical Sensing

    Directory of Open Access Journals (Sweden)

    Disi Lu


    Full Text Available Quantum dots (QDs, have great potential for fabricating optical sensing devices and imaging biomaterial degradation in vivo. In the present study, 2-mercaptoethylamine- (MEA- and mercaptopropionic acid- (MPA- capped CdTe-QDs were physically incorporated in silk films that contained a high content (>30% of crystalline beta-sheet structure. The beta-sheets were induced by the addition of glycerol, water annealing, glycerol/annealing, or treatment with methanol. Incorporation of QDs did not influence the formation of beta-sheets. When the films were extracted with water, most QDs remained associated with the silk, based on the retention of photoluminescence in the silk films and negligible photoluminescence in the extracts. Compared to the solution state, photoluminescence intensity significantly decreased for MEA-QDs but not for MPA-QDs in the silk films, while the emission maximum blue shifted (≈4 nm slightly for both. Further film digestion using protease XIV, alpha-chymotrypsin, and the combination of the two proteases suggested that QDs may be bound to the silk beta-sheet regions but not the amorphous regions. QDs photoluminescence in silk films was quenched when the concentration of hydrogen peroxide (H2O2 was above 0.2-0.3 mM, indicating the QDs-incorporated silk films can be used to report oxidation potential in solution.

  14. Biomaterials with Antibacterial and Osteoinductive Properties to Repair Infected Bone Defects

    Directory of Open Access Journals (Sweden)

    Haiping Lu


    Full Text Available The repair of infected bone defects is still challenging in the fields of orthopedics, oral implantology and maxillofacial surgery. In these cases, the self-healing capacity of bone tissue can be significantly compromised by the large size of bone defects and the potential/active bacterial activity. Infected bone defects are conventionally treated by a systemic/local administration of antibiotics to control infection and a subsequent implantation of bone grafts, such as autografts and allografts. However, these treatment options are time-consuming and usually yield less optimal efficacy. To approach these problems, novel biomaterials with both antibacterial and osteoinductive properties have been developed. The antibacterial property can be conferred by antibiotics and other novel antibacterial biomaterials, such as silver nanoparticles. Bone morphogenetic proteins are used to functionalize the biomaterials with a potent osteoinductive property. By manipulating the carrying modes and release kinetics, these biomaterials are optimized to maximize their antibacterial and osteoinductive functions with minimized cytotoxicity. The findings, in the past decade, have shown a very promising application potential of the novel biomaterials with the dual functions in treating infected bone defects. In this review, we will summarize the current knowledge of novel biomaterials with both antibacterial and osteoinductive properties.

  15. Activation of Macrophages by Lipopolysaccharide for Assessing the Immunomodulatory Property of Biomaterials. (United States)

    Han, Shengwei; Chen, Zetao; Han, Pingping; Hu, Qingang; Xiao, Yin


    The design paradigm of biomaterials has been changed to ones with favorable immunomodulatory effects, indicating the importance of accurately evaluating the immunomodulatory properties of biomaterials. Among all the immune cells macrophages receive most attention, due to their plasticity and multiple roles in the materials and host interactions, and thereby become model immune cells for the evaluation of immunomodulatory properties of biomaterials in many studies. Lipopolysaccharides (LPS), a polysaccharide in the outer membrane of Gram-negative bacteria, elicit strong immune responses, which was often applied to activate macrophages, resulting in a proinflammatory M1 phenotype, and the release of proinflammatory cytokines, including tumor necrosis factor alpha (TNFα), interleukin (IL)-1, and IL-6. However, there is no consensus on how to apply macrophages and LPS to detect the immunomodulatory properties of biomaterials. The lack of scientific consideration of this issue has led to some inaccurate and insufficient conclusions on the immunomodulatory properties of biomaterials, and inconsistences between different research groups. In this study, we carried out a systemic study to investigate the stimulatory effects of LPS with different times, doses, and conditions on the activation of macrophages. An experimental pathway was proposed accordingly for the activation of macrophages using LPS for assessing the immunomodulatory property of biomaterials.

  16. Opportunities and challenges for the development of polymer-based biomaterials and medical devices. (United States)

    Yin, Jinghua; Luan, Shifang


    Biomaterials and medical devices are broadly used in the diagnosis, treatment, repair, replacement or enhancing functions of human tissues or organs. Although the living conditions of human beings have been steadily improved in most parts of the world, the incidence of major human's diseases is still rapidly growing mainly because of the growth and aging of population. The compound annual growth rate of biomaterials and medical devices is projected to maintain around 10% in the next 10 years; and the global market sale of biomaterials and medical devices is estimated to reach $400 billion in 2020. In particular, the annual consumption of polymeric biomaterials is tremendous, more than 8000 kilotons. The compound annual growth rate of polymeric biomaterials and medical devices will be up to 15-30%. As a result, it is critical to address some widespread concerns that are associated with the biosafety of the polymer-based biomaterials and medical devices. Our group has been actively worked in this direction for the past two decades. In this review, some key research results will be highlighted.

  17. Enhancing radiotherapy for lung cancer using immunoadjuvants delivered in situ from new design radiotherapy biomaterials: a preclinical study (United States)

    Hao, Yao; Yasmin-Karim, Sayeda; Moreau, Michele; Sinha, Neeharika; Sajo, Erno; Ngwa, Wilfred


    Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize the toxicities and prime a more potent immune response, Ngwa et al have proposed that inert radiotherapy biomaterials such as fiducials could be upgraded to multifunctional ones loaded with IA for in situ delivery directly into the tumor sub-volume at no additional inconvenience to patients. In this preliminary study, the potential of such an approach is investigated for lung cancer using anti-CD40 antibody. First the benefit of using the anti-CD40 delivered in situ to enhance radiotherapy was tested in mice with subcutaneous tumors generated with the Lewis Lung cancer cell line LL/2 (LLC-1). The tumors were implanted on both flanks of the mice to simulate metastasis. Tumors on one flank were treated with and without anti-CD40 and the survival benefits compared. An experimentally determined in vivo diffusion coefficient for nanoparticles was then employed to estimate the time for achieving intratumoral distribution of the needed minimal concentrations of anti-CD40 nanoparticles if released from a multifuntional radiotherapy biomaterials. The studies show that the use of anti-CD40 significantly enhanced radiotherapy effect, slowing the growth of the treated and untreated tumors, and increasing survival. Meanwhile our calculations indicate that for a 2-4 cm tumor and 7 mg g-1 IA concentrations, it would take 4.4-17.4 d, respectively, following burst release, for the required concentration of IA nanoparticles to accumulate throughout the tumor during image-guided radiotherapy. The distribution of IA could be customized as a function of loading concentrations or nanoparticle size to fit current

  18. 自主神经介导性晕厥患儿24 h动态血压研究%Ambulatory blood pressure in children with neurally mediated syncope

    Institute of Scientific and Technical Information of China (English)

    陈丽; 陈建军; 金红芳; 唐朝枢; 杜军保


    目的:探讨自主神经介导性晕厥(neurally mediated syncope,NMs)患儿24 h动态血压监测(ambuhtory blood pressure monitoring,ABPM)中各项参数的变化,并分析24 h动态血压变化模式对NMS患儿的诊断价值.方法:2007年7月至2008年3月在北京大学第一医院儿科就诊的NMS患儿47例,其中男20例,女27例,年龄平均(11.7±2.8)岁;同时匹配对照组儿童23例,其中男12例,女11例,平均年龄(11.0±3.2)岁.进行血流动力学类型检测,将NMS患儿分为血管迷走性晕厥(vasovasal syncope,VVS)组[共16例,其中男7例,女9例,平均年龄(11.5±2.8)岁]和体位性心动过速综合征(postural orthostatic tachycardia syndrome,POTS)组[共31例,其中男13例,女18例,年龄平均(11.7±2.9)岁].比较呈现不同血流动力学模式的儿童24 h动态血压中的各项参数的变化及24 h动态血压变化模式对NMS的诊断价值.采用SPSS10.0软件进行统计.结果:POTS组的全天平均舒张压、白天平均舒张压和夜间平均收缩压比对照组分别增高了8.26%、6.66%和6.03%,两组之间差异均有统计学意义(P0.05).与对照组相比,VVS组和POTS组患儿的收缩压昼夜差值分别减少了35.92%和28.42%,两组之间差异均有统计学意义(P0.05).24 h血压波动曲线结果表明,在VVS组及POTS组中,呈现"非勺型"者的比例均明显高于对照组(68.8%vs17.4%,64.5%vs17.4%,P0.05).24 h血压"非勺型"对于诊断NMS的敏感度为66.0%,特异度为82.6%,诊断符合率为71.4%.结论:NMS患儿的自主神经功能调节失衡,24 h动态血压变化模式对NMS具有诊断价值.

  19. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans. (United States)

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi


    The replenishment of adiponectin-an adipocyte-derived hormone with salutary health effects-has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.

  20. Biomaterial imaging with MeV-energy heavy ion beams

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Toshio, E-mail: [Department of Nuclear Engineering, Kyoto Univ., Uji, Kyoto 611-0011 (Japan); CREST, Japan Science and Technology Agency (JST), Chiyoda, Tokyo 102-0075 (Japan); Wakamatsu, Yoshinobu; Nakagawa, Shunichiro [Department of Nuclear Engineering, Kyoto Univ., Uji, Kyoto 611-0011 (Japan); Aoki, Takaaki [Department of Electronic Science and Engineering, Kyoto Univ., Nishikyo, Kyoto 615-8510 (Japan); CREST, Japan Science and Technology Agency (JST), Chiyoda, Tokyo 102-0075 (Japan); Ishihara, Akihiko [Laboratory of Cell Biology and Life Science, Graduate School of Human and Environmental Studies, Kyoto Univ., Sakyo, Kyoto 606-8501 (Japan); Matsuo, Jiro [Quantum Science and Engineering Center, Kyoto Univ., Uji, Kyoto 611-0011 (Japan); CREST, Japan Science and Technology Agency (JST), Chiyoda, Tokyo 102-0075 (Japan)


    The spatial distribution of several chemical compounds in biological tissues and cells can be obtained with mass spectrometry imaging (MSI). In conventional secondary ion mass spectrometry (SIMS) with keV-energy ion beams, elastic collisions occur between projectiles and atoms of constituent molecules. The collisions produce fragments, making the acquisition of molecular information difficult. In contrast, ion beams with MeV-energy excite near-surface electrons and enhance the ionization of high-mass molecules; hence, SIMS spectra of fragment-suppressed ionized molecules can be obtained with MeV-SIMS. To compare between MeV and conventional SIMS, we used the two methods based on MeV and Bi{sub 3}-keV ions, respectively, to obtain molecular images of rat cerebellum. Conventional SIMS images of m/z 184 were clearly observed, but with the Bi{sub 3} ion, the distribution of the molecule with m/z 772.5 could be observed with much difficulty. This effect was attributed to the low secondary ion yields and we could not get many signal counts with keV-energy beam. On the other hand, intact molecular ion distributions of lipids were clearly observed with MeV-SIMS, although the mass of all lipid molecules was higher than 500 Da. The peaks of intact molecular ions in MeV-SIMS spectra allowed us to assign the mass. The high secondary ion sensitivity with MeV-energy heavy ions is very useful in biomaterial analysis.

  1. Gellan gum: a new biomaterial for cartilage tissue engineering applications. (United States)

    Oliveira, J T; Martins, L; Picciochi, R; Malafaya, P B; Sousa, R A; Neves, N M; Mano, J F; Reis, R L


    Gellan gum is a polysaccharide manufactured by microbial fermentation of the Sphingomonas paucimobilis microorganism, being commonly used in the food and pharmaceutical industry. It can be dissolved in water, and when heated and mixed with mono or divalent cations, forms a gel upon lowering the temperature under mild conditions. In this work, gellan gum hydrogels were analyzed as cells supports in the context of cartilage regeneration. Gellan gum hydrogel discs were characterized in terms of mechanical and structural properties. Transmissionelectron microscopy revealed a quite homogeneous chain arrangement within the hydrogels matrix, and dynamic mechanical analysis allowed to characterize the hydrogels discs viscoelastic properties upon compression solicitation, being the compressive storage and loss modulus of approximately 40 kPa and 3 kPa, respectively, at a frequency of 1 Hz. Rheological measurements determined the sol-gel transition started to occur at approximately 36 degrees C, exhibiting a gelation time of approximately 11 s. Evaluation of the gellan gum hydrogels biological performance was performed using a standard MTS cytotoxicity test, which showed that the leachables released are not deleterious to the cells and hence were noncytotoxic. Gellan gum hydrogels were afterwards used to encapsulate human nasal chondrocytes (1 x 10(6) cells/mL) and culture them for total periods of 2 weeks. Cells viability was confirmed using confocal calcein AM staining. Histological observations revealed normal chondrocytes morphology and the obtained data supports the claim that this new biomaterial has the potential to serve as a cell support in the field of cartilage regeneration.

  2. Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans (United States)

    Ngatu, Nlandu Roger; Ikeda, Mitsunori; Watanabe, Hiroyuki; Tanaka, Mamoru; Inoue, Masataka; Kanbara, Sakiko; Nojima, Sayumi


    The replenishment of adiponectin—an adipocyte-derived hormone with salutary health effects—has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans. PMID:28208744

  3. Measurements of optical polarization properties in dental tissues and biomaterials (United States)

    Fernández-Oliveras, Alicia; Pecho, Oscar E.; Rubiño, Manuel; Pérez, María M.


    Since biological tissues can have the intrinsic property of altering the polarization of incident light, optical polarization studies are important for a complete characterization. We have measured the polarized light scattered off of different dental tissues and biomaterials for a comparative study of their optical polarization property. The experimental setup was composed by a He-Ne laser, two linear polarizers and a detection system based on a photodiode. The laser beam was passed through one linear polarizer placed in front of the sample, beyond which the second linear polarizer (analyzer) and the photodiode detector were placed. First, the maximum laser-light intensity (reference condition) was attained without the sample in the laser path. Then, the sample was placed between the two polarizers and the polarization shift of the scattered laser light was determined by rotating the analyzer until the reference condition was reached. Two dental-resin composites (nanocomposite and hybrid) and two human dental tissues (enamel and dentine) were analyzed under repeatability conditions at three different locations on the sample: 20 measurements of the shift were taken and the average value and the uncertainty associated were calculated. For the human dentine the average value of the polarization shift found was 7 degrees, with an associated uncertainty of 2 degrees. For the human enamel and both dental-resin composites the average shift values were found to be similar to their corresponding uncertainties (2 degrees). The results suggest that although human dentine has notable polarization properties, dental-resin composites and human enamel do not show significant polarization shifts.

  4. Staphylococcus epidermidis adhesion on hydrophobic and hydrophilic textured biomaterial surfaces. (United States)

    Xu, Li-Chong; Siedlecki, Christopher A


    It is of great interest to use nano- or micro-structured surfaces to inhibit microbial adhesion and biofilm formation and thereby to prevent biomaterial-associated infection, without modification of the surface chemistry or bulk properties of the materials and without use of the drugs. Our previous study showed that a submicron textured polyurethane surface can inhibit staphylococcal bacterial adhesion and biofilm formation. To further understand the effect of the geometry of textures on bacterial adhesion as well as the underlying mechanism, in this study, submicron and micron textured polyurethane surfaces featuring ordered arrays of pillars were fabricated and modified to have different wettabilities. All the textured surfaces were originally hydrophobic and showed significant reductions in Staphylococcus epidermidis RP62A adhesion in phosphate buffered saline or 25% platelet poor plasma solutions under shear, as compared to smooth surfaces. After being subjected to an air glow discharge plasma treatment, all polyurethane surfaces were modified to hydrophilic, and reductions in bacterial adhesion on surfaces were subsequently found to be dependent on the size of the patterns. The submicron patterned surfaces reduced bacterial adhesion, while the micron patterned surfaces led to increased bacterial adhesion. The extracellular polymeric substances (EPS) from the S. epidermidis cell surfaces were extracted and purified, and were coated on a glass colloidal surface so that the adhesion force and separation energy in interactions of the EPS and the surface could be measured by colloidal probe atomic force microscopy. These results were consistent with the bacterial adhesion observations. Overall, the data suggest that the increased surface hydrophobicity and the decreased availability of the contact area contributes to a reduction in bacterial adhesion to the hydrophobic textured surfaces, while the availability of the contact area is the primary determinant factor

  5. MO-FG-BRA-05: Next Generation Radiotherapy Biomaterials Loaded With Gold Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Cifter, G; Ngwa, W [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (United States); Univ Massachusetts Lowell, Lowell, MA (United States); Sajo, E [Univ Massachusetts Lowell, Lowell, MA (United States); Korideck, H; Cormack, R; Makrigiorgos, G [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (United States); Kumar, R [Dana Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (United States); Northeastern University, Boston, MA (United States); Sridhar, S [Northeastern University, Boston, MA (United States)


    Purpose: It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. In this work, we developed prototypes of such RT biomaterials and investigated the sustained release of GNPs from the biomaterials as a function of design parameters. Methods: Prototype smart biomaterials were produced by incorporating the GNPs in poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. For comparison, commercially available spacers were also coated with a polymer film loaded with fluorescent GNP. Optical/spectroscopy methods were used to monitor in vitro release of GNPs over time as a function of different design parameters: polymer weighting, type, and initial (loading) GNP concentrations. Inductively coupled plasma mass spectrometry was employed to verify GNP release. Results: Results showed that gold nanoparticles could be successfully loaded in the new RT biomaterial prototypes. Burst release of GNPs could be achieved within 1 to 25 days depending on the preparation approach. Burst release was followed by sustained release profile over time. The amount of released GNP increased with increasing loading concentration as expected. The release profiles could also be customized as a function of polymer weighting, or preparation approaches. Conclusion: Considered together, our results highlight potential for the development of next generation RT biomaterials loaded with GNPs customizable to different RT schedules. Such biomaterials could be employed as needed instead of currently used inert spacers/fiducials at no additional inconvenience to patients, to enhance RT.

  6. Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends. (United States)

    Qazi, Taimoor H; Mooney, David J; Pumberger, Matthias; Geissler, Sven; Duda, Georg N


    Skeletal muscles have a robust capacity to regenerate, but under compromised conditions, such as severe trauma, the loss of muscle functionality is inevitable. Research carried out in the field of skeletal muscle tissue engineering has elucidated multiple intrinsic mechanisms of skeletal muscle repair, and has thus sought to identify various types of cells and bioactive factors which play an important role during regeneration. In order to maximize the potential therapeutic effects of cells and growth factors, several biomaterial based strategies have been developed and successfully implemented in animal muscle injury models. A suitable biomaterial can be utilized as a template to guide tissue reorganization, as a matrix that provides optimum micro-environmental conditions to cells, as a delivery vehicle to carry bioactive factors which can be released in a controlled manner, and as local niches to orchestrate in situ tissue regeneration. A myriad of biomaterials, varying in geometrical structure, physical form, chemical properties, and biofunctionality have been investigated for skeletal muscle tissue engineering applications. In the current review, we present a detailed summary of studies where the use of biomaterials favorably influenced muscle repair. Biomaterials in the form of porous three-dimensional scaffolds, hydrogels, fibrous meshes, and patterned substrates with defined topographies, have each displayed unique benefits, and are discussed herein. Additionally, several biomaterial based approaches aimed specifically at stimulating vascularization, innervation, and inducing contractility in regenerating muscle tissues are also discussed. Finally, we outline promising future trends in the field of muscle regeneration involving a deeper understanding of the endogenous healing cascades and utilization of this knowledge for the development of multifunctional, hybrid, biomaterials which support and enable muscle regeneration under compromised conditions.

  7. Minimally Invasive Surgery Combined with Regenerative Biomaterials in Treating Intra-Bony Defects: A Meta-Analysis


    Shan Liu; Bo Hu; Yuanyuan Zhang; Wenyang Li; Jinlin Song


    Background With the popularity of minimally invasive surgery (MIS) in periodontics, numerous publications have evaluated the benefits of MIS with or without various regenerative biomaterials in the treatment of periodontal intra-bony defects. However, it is unclear if it is necessary to use biomaterials in MIS. Thus, we conducted a meta-analysis of randomized clinical trials in patients with intra-bony defects to compare the clinical outcomes of MIS with regenerative biomaterials for MIS alon...

  8. Semaphorin signaling in vertebrate neural circuit assembly

    Directory of Open Access Journals (Sweden)

    Yutaka eYoshida


    Full Text Available Neural circuit formation requires the coordination of many complex developmental processes. First, neurons project axons over long distances to find their final targets and then establish appropriate connectivity essential for the formation of neuronal circuitry. Growth cones, the leading edges of axons, navigate by interacting with a variety of attractive and repulsive axon guidance cues along their trajectories and at final target regions. In addition to guidance of axons, neuronal polarization, neuronal migration and dendrite development must be precisely regulated during development to establish proper neural circuitry. Semaphorins consist of a large protein family, which includes secreted and cell surface proteins, and they play important roles in many steps of neural circuit formation. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors also mediate signaling by semaphorins. Upon semaphorin binding to their receptors, downstream signaling molecules transduce this event within cells to mediate further events, including alteration of microtubule and actin cytoskeletal dynamics. Here, I review recent studies on semaphorin signaling in vertebrate neural circuit assembly, with the goal of highlighting how this diverse family of cues and receptors imparts exquisite specificity to neural complex connectivity.

  9. Neural Tube Defects (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  10. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)


    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  11. Artificial Neural Networks


    Chung-Ming Kuan


    Artificial neural networks (ANNs) constitute a class of flexible nonlinear models designed to mimic biological neural systems. In this entry, we introduce ANN using familiar econometric terminology and provide an overview of ANN modeling approach and its implementation methods.

  12. Differentiation state determines neural effects on microvascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Muffley, Lara A., E-mail: [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Pan, Shin-Chen, E-mail: [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Smith, Andria N., E-mail: [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Ga, Maricar, E-mail: [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Hocking, Anne M., E-mail: [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States); Gibran, Nicole S., E-mail: [University of Washington, Campus Box 359796, 300 9th Avenue, Seattle, WA 98104 (United States)


    microvascular endothelial cell production of nitric oxide. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons have different secretory profiles for angiogenic mediators.

  13. Study of the biodegradation and in vivo biocompatibility of novel biomaterials. (United States)

    Fulzele, S V; Satturwar, P M; Dorle, A K


    The degradation of two rosin-based biomaterials, the glycerol ester of maleic rosin (GMR) and the pentaerythritol ester of maleic rosin (PMR), was examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a subcutaneous rat model. Free films of the two biomaterials with mean thickness 0.4+/-0.02 mm were used for the study. The initial biocompatibility was followed by microscopic examination of the inflammatory tissue response to the implanted films. Sample weight loss and molecular weight decline of the free films was used to monitor the degradation quantitatively, while surface morphological changes were analysed for qualitative estimation. Biocompatibility response was followed on post-operative days 7, 14, 21 and 28 and compared with those of poly(DL-lactic-co-glycolic acid) (PLGA) (50:50) films. Both biomaterials showed slow in vitro degradation when compared with the in vivo rate. The mechanism followed was, however, bulk degradation of the films. The penta-esterified form of maleic rosin was observed to degrade more rapidly than glycerol esterified maleic rosin. The acute and subacute inflammatory reactions were characterized by fibrosis at the end of 28 days. The biomaterials showed reasonable tissue tolerance to the extent evaluated. There was a total absence of tissue necrosis or abscess formation for all implanted films. The response, although not identical to that of PLGA, is reasonable, promising new drug delivery applications for rosin biomaterials.

  14. Adherence ability of Staphylococcus epidermidis on prosthetic biomaterials: an in vitro study

    Directory of Open Access Journals (Sweden)

    Shida T


    Full Text Available Takayuki Shida,1 Hironobu Koseki,1 Itaru Yoda,1 Hidehiko Horiuchi,1 Hideyuki Sakoda,2 Makoto Osaki11Department of Orthopedic Surgery, Graduate School of Medicine, Nagasaki University, Nagasaki, Japan; 2Division of Medical Devices, National Institute of Health Sciences, Tokyo, JapanAbstract: Bacterial adhesion to the surface of biomaterials is an essential step in the pathogenesis of implant-related infections. In this in vitro research, we evaluated the ability of Staphylococcus epidermidis to adhere to the surface of solid biomaterials, including oxidized zirconium-niobium alloy (Oxinium, cobalt-chromium-molybdenum alloy, titanium alloy, commercially pure titanium, and stainless steel, and performed a biomaterial-to-biomaterial comparison. The test specimens were physically analyzed to quantitatively determine the viable adherent density of the S. epidermidis strain RP62A (American Type Culture Collection [ATCC] 35984. Field emission scanning electron microscope and laser microscope examination revealed a featureless, smooth surface in all specimens (average roughness <10 nm. The amounts of S. epidermidis that adhered to the biomaterial were significantly lower for Oxinium and the cobalt-chromium-molybdenum alloy than for commercially pure titanium. These results suggest that Oxinium and cobalt-chromium-molybdenum alloy are less susceptible to bacterial adherence and are less inclined to infection than other materials of a similar degree of smoothness.Keyword: bacterial adhesion, implant, infection, surface character

  15. Smooth muscle cell phenotype alters cocultured endothelial cell response to biomaterial-pretreated leukocytes. (United States)

    Rose, Stacey L; Babensee, Julia E


    Model in vitro culturing systems were developed to analyze roles of biomaterial-induced leukocyte activation on endothelial cell (EC) and smooth muscle cell (SMC) phenotype, and their crosstalk. Isolated monocytes or neutrophils were pretreated with model biomaterial beads and applied directly to "more secretory" (cultured in media containing 5% fetal bovine serum) or forced contractile (serum and growth factor starved) human aortic SMCs (HASMCs), or to the human aortic EC (HAEC) surface of HAEC/HASMC cocultures (HASMC phenotype varied to be "more or less secretory") for 5 or 24 h of static culture. Surface expression of proinflammatory [ICAM-1, VCAM-1, E-selectin], procoagulant (tissue factor), and anticoagulant (thrombomodulin) markers, as well as HAEC proliferation, were assessed by flow cytometry. Incubation of HAEC with biomaterial-pretreated monocytes (and neutrophils to lesser degree) suppressed HAEC proliferation and induced a proinflammatory/procoagulant HAEC phenotype. This HAEC phenotype was amplified in coculture with "more secretory" HASMCs and subdued in coculture with "less secretory" HASMCs. Direct incubation of biomaterial-pretreated monocytes or neutrophils with "more secretory" HASMCs further increased HASMC ICAM-1 and tissue factor expression. Direct incubation of biomaterial-pretreated monocytes or neutrophils with forced contractile HASMCs upregulated ICAM-1, VCAM-1, and tissue factor expression above the presence of serum-containing media alone.

  16. Bone defect animal models for testing efficacy of bone substitute biomaterials

    Directory of Open Access Journals (Sweden)

    Ye Li


    Full Text Available Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

  17. Advanced biomaterials and their potential applications in the treatment of periodontal disease. (United States)

    Chen, Xi; Wu, Guofeng; Feng, Zhihong; Dong, Yan; Zhou, Wei; Li, Bei; Bai, Shizhu; Zhao, Yimin


    Periodontal disease is considered as a widespread infectious disease and the most common cause of tooth loss in adults. Attempts for developing periodontal disease treatment strategies, including drug delivery and regeneration approaches, provide a useful experimental model for the evaluation of future periodontal therapies. Recently, emerging advanced biomaterials including hydrogels, films, micro/nanofibers and particles, hold great potential to be utilized as cell/drug carriers for local drug delivery and biomimetic scaffolds for future regeneration therapies. In this review, first, we describe the pathogenesis of periodontal disease, including plaque formation, immune response and inflammatory reactions caused by bacteria. Second, periodontal therapy and an overview of current biomaterials in periodontal regenerative medicine have been discussed. Third, the roles of state-of-the-art biomaterials, including hydrogels, films, micro/nanofibers and micro/nanoparticles, developed for periodontal disease treatment and periodontal tissue regeneration, and their fabrication methods, have been presented. Finally, biological properties, including biocompatibility, biodegradability and immunogenicity of the biomaterials, together with their current applications strategies are given. Conclusive remarks and future perspectives for such advanced biomaterials are discussed.

  18. Intercultural Mediation


    Dragos Marian Radulescu; Denisa Mitrut


    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  19. Neural tissue-spheres

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten


    By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...


    NARCIS (Netherlands)



    Traditional approaches to neural coding characterize the encoding of known stimuli in average neural responses. Organisms face nearly the opposite task - extracting information about an unknown time-dependent stimulus from short segments of a spike train. Here the neural code was characterized from

  1. Generalized classifier neural network. (United States)

    Ozyildirim, Buse Melis; Avci, Mutlu


    In this work a new radial basis function based classification neural network named as generalized classifier neural network, is proposed. The proposed generalized classifier neural network has five layers, unlike other radial basis function based neural networks such as generalized regression neural network and probabilistic neural network. They are input, pattern, summation, normalization and output layers. In addition to topological difference, the proposed neural network has gradient descent based optimization of smoothing parameter approach and diverge effect term added calculation improvements. Diverge effect term is an improvement on summation layer calculation to supply additional separation ability and flexibility. Performance of generalized classifier neural network is compared with that of the probabilistic neural network, multilayer perceptron algorithm and radial basis function neural network on 9 different data sets and with that of generalized regression neural network on 3 different data sets include only two classes in MATLAB environment. Better classification performance up to %89 is observed. Improved classification performances proved the effectivity of the proposed neural network.

  2. Novel nanostructured biomaterials: implications for coronary stent thrombosis

    Directory of Open Access Journals (Sweden)

    Karagkiozaki V


    Full Text Available Varvara Karagkiozaki,1,2 Panagiotis G Karagiannidis,1 Nikolaos Kalfagiannis,1 Paraskevi Kavatzikidou,1 Panagiotis Patsalas,3 Despoina Georgiou,1 Stergios Logothetidis11Lab for Thin Films – Nanosystems and Nanometrology (LTFN, Physics Department, Aristotle University of Thessaloniki, Thessaloniki, 2AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, 3Department of Materials Science and Engineering, University of Ioannina, Ioannina, Epirus, GreeceBackground: Nanomedicine has the potential to revolutionize medicine and help clinicians to treat cardiovascular disease through the improvement of stents. Advanced nanomaterials and tools for monitoring cell–material interactions will aid in inhibiting stent thrombosis. Although titanium boron nitride (TiBN, titanium diboride, and carbon nanotube (CNT thin films are emerging materials in the biomaterial field, the effect of their surface properties on platelet adhesion is relatively unexplored.Objective and methods: In this study, novel nanomaterials made of amorphous carbon, CNTs, titanium diboride, and TiBN were grown by vacuum deposition techniques to assess their role as potential stent coatings. Platelet response towards the nanostructured surfaces of the samples was analyzed in line with their physicochemical properties. As the stent skeleton is formed mainly of stainless steel, this material was used as reference material. Platelet adhesion studies were carried out by atomic force microscopy and scanning electron microscopy observations. A cell viability study was performed to assess the cytocompatibility of all thin film groups for 24 hours with a standard immortalized cell line.Results: The nanotopographic features of material surface, stoichiometry, and wetting properties were found to be significant factors in dictating platelet behavior and cell viability. The TiBN films with higher nitrogen contents were less thrombogenic compared with the biased carbon films and control

  3. Polymer biomaterial constructs for regenerative medicine and functional biological systems (United States)

    Meng, Linghui

    The use of collagen as a biomaterial is currently undergoing a renaissance in the tissue engineering field. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenicity, make collagen a primary material resource in medical applications. Described herein is work towards the development of novel collagen-based matrices, with additional multi-functionality imparted through a novel in-situ crosslinking approach. The process of electrospinning has become a widely used technique for the creation of fibrous scaffolds for tissue engineering applications due to its ability to rapidly create structures composed of nano-scale polymer fibers closely resembling the architecture of the extracellular matrix (ECM). Collagen-PCL sheath-core bicomponent fibrous scaffolds were fabricated using a novel variation on traditional electrospinning, known as co-axial electrospinning. The results showed that the addition of a synthetic polymer core into collagen nanofibers remarkably increased the mechanical strength of collagen matrices spun from the benign solvent system. A novel single-step, in-situ collagen crosslink approach was developed in order to solve the problems dominating traditional collagen crosslinking methods, such as dimensional shrinking and loss of porous morphology, and to simplify the crosslinking procedure for electrospun collagen scaffolds. The excess amount of NHS present in the crosslinking mixture was found to delay the EDC/collagen coupling reaction in a controlled fashion. Fundamental investigations into the development and characterization of in-situ crosslinked collagen matrices such as fibrous scaffolds, gels and sponges, as well as their biomedical applications including cell culture substrates, wound dressings, drug delivery matrices and bone regeneration substitutes, were performed. The preliminary mice studies indicated that the in-situ crosslinked collagen matrices could be good candidates

  4. Influence of therapeutic radiation on polycaprolactone and polyurethane biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, Shelley L. [Department of Materials Science and Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Whittington, Abby R., E-mail: [Department of Materials Science and Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States); Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 (United States)


    irradiation. Results from both PCL and PU suggest changes in polymer backbones. This preliminary study suggests that therapeutic radiation doses cause both degradation and crosslinking in PCL and PU. - Highlights: • Investigation of therapeutic radiation on polycaprolactone and polyurethane • Chemical and physical changes were evaluated and characterized in vitro. • Polycaprolactone displayed few changes due to irradiation. • Polyurethane displayed significant changes after irradiation. • In vivo studies are underway with biomaterials exposed to therapeutic radiation.

  5. [Neural basis of maternal behavior]. (United States)

    Noriuchi, Madoka; Kikuchi, Yoshiaki


    Maternal love, which may be the core of maternal behavior, is essential for the mother-infant attachment relationship and is important for the infant's development and mental health. However, little has been known about these neural mechanisms in human mothers. We examined patterns of maternal brain activation in response to infant cues using video clips. We performed functional magnetic resonance imaging (fMRI) measurements while 13 mothers viewed video clips, with no sound, of their own infant and other infants of approximately 16 months of age who demonstrated two different attachment behaviors (smiling at the infant's mother and crying for her). We found that a limited number of the mother's brain areas were specifically involved in recognition of the mother's own infant, namely orbitofrontal cortex (OFC). and periaqueductal gray, anterior insula, and dorsal and ventrolateral parts of putamen. Additionally, we found the strong and specific mother's brain response for the mother's own infant's distress. The differential neural activation pattern was found in the dorsal region of OFC, caudate nucleus, right inferior frontal gyrus, dorsomedial prefrontal cortex (PFC), anterior cingulate, posterior cingulate, posterior superior temporal sulcus, and dorsolateral PFC. Our results showed the highly elaborate neural mechanism mediating maternal love and diverse and complex maternal behaviors for vigilant protectiveness.

  6. Preparation and characterization of Ti-15Mo alloy used as biomaterial

    Directory of Open Access Journals (Sweden)

    José Roberto Severino Martins Júnior


    Full Text Available With the increase in life expectancy, biomaterials have become an increasingly important focus of research because they are used to replace parts and functions of the human body, thus contributing to improved quality of life. In the development of new biomaterials, the Ti-15Mo alloy is particularly significant. In this study, the Ti-15Mo alloy was produced using an arc-melting furnace and then characterized by density, X-ray diffraction, optical microscopy, hardness and dynamic elasticity modulus measurements, and cytotoxicity tests. The microstructure was obtained with β predominance. Microhardness, elasticity modulus, and cytotoxicity testing results showed that this material has great potential for use as biomaterial, mainly in orthopedic applications.

  7. Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics. (United States)

    Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Cheng, Chao-Min


    Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed.

  8. The use of calcium phosphate-based biomaterials in implant dentistry. (United States)

    Xie, Cheng; Lu, Hong; Li, Wei; Chen, Fa-Ming; Zhao, Yi-Min


    Since calcium phosphates (CaPs) were first proposed, a wide variety of formulations have been developed and continuously optimized, some of which (e.g. calcium phosphate cements, CPCs) have been successfully commercialized for clinical applications. These CaP-based biomaterials have been shown to be very attractive bone substitutes and efficient drug delivery vehicles across diverse biomedical applications. In this article, CaP biomaterials, principally CPCs, are addressed as alternatives/complements to autogenous bone for grafting in implant dentistry and as coating materials for enhancing the osteoinductivity of titanium implants, highlighting their performance benefits simultaneously as carriers for growth factors and as scaffolds for cell proliferation, differentiation and penetration. Different strategies for employing CaP biomaterials in dental implantology aim to ultimately reach the same goal, namely to enhance the osseointegration process for dental implants in the context of immediate loading and to augment the formation of surrounding bone to guarantee long-term success.

  9. Assessment of bone healing in rabbit calvaria grafted with three different biomaterials. (United States)

    Takauti, Carlos Alberto Yoshihiro; Futema, Fabio; Brito Junior, Rui Barbosa de; Abrahão, Aline Corrêa; Costa, Claudio; Queiroz, Celso Silva


    This study evaluated the bone regeneration process in rabbit calvaria induced by three types of biomaterials: two xenogenous, consisting of deproteinized bovine bone, while the other was alloplastic, based on biphasic calcium phosphate. Five New Zealand white rabbits weighing between 2,900 and 3,500 g were submitted to four standard 8 mm-diameter perforations at the parietal bone. Three perforations were filled with three grafts and biomaterials, two of them received bovine Bio-Oss® and Endobon® Xenograft Granules, and the other consisted of fully alloplastic Straumann® Bone Ceramic. The fourth remaining cavity was used as control with coagulum. After eight weeks, the animals were sacrificed, and the samples were prepared for morphometric and qualitative analysis. The cavities filled with alloplastic biomaterials showed higher percentages of newly formed bone (pbiomaterials showed higher amount of residual graft (pbiomaterial for bone induction process.

  10. New method of synthesis and in vitro studies of a porous biomaterial

    Energy Technology Data Exchange (ETDEWEB)

    Wers, E., E-mail: [Equipe Chimie du Solide et Matériaux, UMR CNRS 6226, Sciences Chimiques de Rennes, Université de Rennes 1, Université Européenne de Bretagne, 263 avenue du Général Leclerc, 35042 Rennes Cedex (France); Lefeuvre, B. [Equipe Chimie du Solide et Matériaux, UMR CNRS 6226, Sciences Chimiques de Rennes, Université de Rennes 1, Université Européenne de Bretagne, 263 avenue du Général Leclerc, 35042 Rennes Cedex (France); Pellen-Mussi, P.; Novella, A. [Equipe Chimie du Solide et Matériaux, UMR CNRS 6226, Sciences Chimiques de Rennes, Université de Rennes 1, Université Européenne de Bretagne, 2 avenue du Professeur Léon Bernard, 35042 Rennes Cedex (France); Oudadesse, H. [Equipe Chimie du Solide et Matériaux, UMR CNRS 6226, Sciences Chimiques de Rennes, Université de Rennes 1, Université Européenne de Bretagne, 263 avenue du Général Leclerc, 35042 Rennes Cedex (France)


    Biomaterials for bone reconstruction represent a widely studied area. In this paper, a new method of synthesis of a porous glass–ceramic obtained by thermal treatment is presented. The prepared biomaterial was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and induced couple plasma-optical emission spectroscopy (ICP-OES), mercury porosimetry and by the Archimedes method. In vitro evaluations in a simulated body fluid (SBF) and in contact with SaOS{sub 2} human osteoblasts were also carried out. The porous glass–ceramic is composed of a total porous network of 60% suitable for body fluid and cell infiltration, with pore sizes varying from 60 nm to 143 μm. The presence of two crystalline phases decreases the kinetic of bioactivity compared to an amorphous biomaterial (bioactive glass). A hydroxyapatite layer appears from 15 days of immersion on the surface and inside the pores, showing a biodegradation and a bioactivity in four steps. Cytotoxicity assessments present an increase of the cellular viability after 72 h proving the non-cytotoxic effect of the glass–ceramic. Thus, the results of these different studies indicate that the porous biomaterial may have a potential application for the bone regeneration. This paper also presents the novelty of this method. It is a rapid synthesis which combines simplicity and low cost. This represents an advantage for an eventual industrialization. - Highlights: • The new method of synthesis of a porous glass–ceramic is reproducible. • The porous glass–ceramic possesses a total porosity of 60%. • The biomaterial shows a bioactivity in four steps with hydroxyapatite formation. • 82% of cellular viability is observed on the surface of the biomaterial.

  11. The quest for anti-inflammatory and anti-infective biomaterials in clinical translation

    Directory of Open Access Journals (Sweden)

    May Griffith


    Full Text Available Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multi-functional biomaterials with combined properties that can combat infections, modulate inflammation and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC, to silver nanoparticles that have anti-bacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is

  12. The Quest for Anti-inflammatory and Anti-infective Biomaterials in Clinical Translation (United States)

    Griffith, May; Islam, Mohammad M.; Edin, Joel; Papapavlou, Georgia; Buznyk, Oleksiy; Patra, Hirak K.


    Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation. Different strategies are needed to address the regeneration of organs that have been damaged by infection or inflammation for successful clinical translation. Therefore, the real quest is for multifunctional biomaterials with combined properties that can combat infections, modulate inflammation, and promote regeneration at the same time. These strategies will necessitate the inclusion of methodologies for management of the cellular and signaling components elicited within the local microenvironment. In the development of such biomaterials, strategies range from the inclusion of materials that have intrinsic anti-inflammatory properties, such as the synthetic lipid polymer, 2-methacryloyloxyethyl phosphorylcholine (MPC), to silver nanoparticles that have antibacterial properties, to inclusion of nano- and micro-particles in biomaterials composites that deliver active drugs. In this present review, we present examples of both kinds of materials in each group along with their pros and cons. Thus, as a promising next generation strategy to aid or replace tissue/organ transplantation, an integrated smart programmable platform is needed for regenerative medicine applications to create and/or restore normal function at the cell and tissue levels. Therefore, now it is of utmost

  13. Neural induction and factors that stabilize a neural fate


    Rogers, Crystal; Moody, Sally A.; Casey, Elena


    The neural ectoderm of vertebrates forms when the BMP signaling pathway is suppressed. Herein we review the molecules that directly antagonize extracellular BMP and the signaling pathways that further contribute to reduce BMP activity in the neural ectoderm. Downstream of neural induction, a large number of “neural fate stabilizing” (NFS) transcription factors are expressed in the presumptive neural ectoderm, developing neural tube, and ultimately in neural stem cells. Herein we review what i...

  14. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    In contemporary consciousness studies the phenomenon of neural plasticity has received little attention despite the fact that neural plasticity is of still increased interest in neuroscience. We will, however, argue that neural plasticity could be of great importance to consciousness studies....... If consciousness is related to neural processes it seems, at least prima facie, that the ability of the neural structures to change should be reflected in a theory of this relationship "Neural plasticity" refers to the fact that the brain can change due to its own activity. The brain is not static but rather...... the relation between consciousness and brain functions. If consciousness is connected to specific brain structures (as a function or in identity) what happens to consciousness when those specific underlying structures change? It is therefore possible that the understanding and theories of neural plasticity can...




    En este artículo se presenta el fenómeno de adsorción química como una opción viable en el tratamiento de aguas residuales que contiene disueltos iones metálicos, específicamente se aborda el estudio del Cromo Hexavalente, el cual se puso en contacto con el biomaterial de Ectodermis de Opuntia. Dicho biomaterial se puso en contacto con soluciones de dicho elemento solo y formando un complejo coloreado con la difenilcarbazida (DFC), esto con la finalidad de estudiar el comportamiento de la ads...

  16. Preparation and Properties of Collagen-Chitosan/ Glycosaminoglycans as Candidate Tissue Engineering Biomaterials

    Institute of Scientific and Technical Information of China (English)

    LIQin-Hua; HUANGYao-xiong; CHENGJian-su


    A novel biomaterial scaffold was created from collagen-chitosan/GAG. Its tensile strength was 8.6MPa(wet state)and degree of swelling water was 60%~75% with higer ultimate elongation 300%. Rabbit corneas of collagen-chitosan/GAG implantation samples in vivo for biodegradation showed that the inplantion samples was complets biodegrable and digested afere 120 day. There was enought time to maintain cell growth,immigrating and proliferation. This biomaterials scaffold can be used for cell culture and in various tissue engineering fields.

  17. Characterization of cell cultures in contact with different orthopedic implants biomaterials (United States)

    Ouenzerfi, G.; Hannoun, A.; Hassler, M.; Brizuela, L.; Youjil, S.; Bougault, C.; Trunfio-Sfarghiu, A.-M.


    The aim of this study is to identify the role of biological and mechanical constraints (at the cellular level) surrounding living tissues (cartilage and bone) in the presence of different joint implant biomaterials. In this fact, cells cultures in the presence of different types of biomaterials (pyrolytic carbon, cobalt-Chromium, titanium) has been performed. These cell cultures were subjected to biological characterization tests and mechanical characterization. The obtained results correlate with the in vivo observations (a promotion of the creation of a neocartilagical tissue in contact with the Pyrolytic Carbon implants).

  18. Biomaterial-engineering and neurobiological approaches for regenerating the injured cerebral cortex

    Directory of Open Access Journals (Sweden)

    Itsuki Ajioka


    Full Text Available The cerebral cortex is responsible for higher functions of the central nervous system (CNS, such as movement, sensation, and cognition. When the cerebral cortex is severely injured, these functions are irreversibly impaired. Although recent neurobiological studies reveal that the cortex has the potential for regeneration, therapies for functional recovery face some technological obstacles. Biomaterials have been used to evoke regenerative potential and promote regeneration in several tissues, including the CNS. This review presents a brief overview of new therapeutic strategies for cortical regeneration from the perspectives of neurobiology and biomaterial engineering, and discusses a promising technology for evoking the regenerative potential of the cerebral cortex.

  19. The risk of biomaterial-associated infection after revision surgery due to an experimental primary implant infection

    NARCIS (Netherlands)

    Engelsman, Anton F.; Saldarriaga-Fernandez, Isabel C.; Nejadnik, M. Reza; van Dam, Gooitzen M.; Francis, Kevin P.; Ploeg, Rutger J.; Busscher, Henk J.; van der Mei, Henny C.


    The fate of secondary biomaterial implants was determined by bio-optical imaging and plate counting, after antibiotic treatment of biomaterials-associated-infection (BAI) and surgical removal of an experimentally infected, primary implant. All primary implants and tissue samples from control mice sh

  20. The risk of biomaterial-associated infection after revision surgery due to an experimental primary implant infection.

    NARCIS (Netherlands)

    Engelsman, A.F.; Saldarriaga Fernandez, I.C.; Nejadnik, M.R.; Dam, G.M. van; Francis, K.P.; Ploeg, R.J.; Busscher, H.J.; Mei, H.C. van der


    The fate of secondary biomaterial implants was determined by bio-optical imaging and plate counting, after antibiotic treatment of biomaterials-associated-infection (BAI) and surgical removal of an experimentally infected, primary implant. All primary implants and tissue samples from control mice sh

  1. Mold-Based Application of Laser-Induced Periodic Surface Structures (LIPSS) on Biomaterials for Nanoscale Patterning

    NARCIS (Netherlands)

    Hendrikson, Wim; Masman-Bakker, Wendy; van Bochove, Bas; Skolski, Johann; Eichstadt, Justus; Koopman, Bart; van Blitterswijk, Clemens; Grijpma, Dirk; Romer, Gert-Willem; Moroni, Lorenzo; Rouwkema, Jeroen


    Laser-induced periodic surface structures (LIPSS) are highly regular, but at the same time contain a certain level of disorder. The application of LIPSS is a promising method to functionalize biomaterials. However, the absorption of laser energy of most polymer biomaterials is insufficient for the d

  2. Mold-based application of laser-induced periodic surface structures (LIPPS) on biomaterials for nanoscale patterning

    NARCIS (Netherlands)

    Hendrikson, W.J.; Masman-Bakker, W.; Bochove, van J.B.; Skolski, J.Z.P.; Eichstädt, J.; Koopman, H.F.J.M.; Blitterswijk, van C.A.; Grijpma, D.W.; Römer, G.R.B.E.; Moroni, L.; Rouwkema, J.


    Laser-induced periodic surface structures (LIPSS) are highly regular, but at the same time contain a certain level of disorder. The application of LIPSS is a promising method to functionalize biomaterials. However, the absorption of laser energy of most polymer biomaterials is insufficient for the d


    NARCIS (Netherlands)



    Although in the last few years in general the biocompatibility of biomaterials has significantly improved, unwanted tissue reactions are often observed resulting in early resorption of the biomaterial, loosening of the implant or in a chronic (immunologic) response. From immunologic studies it is kn

  4. Microbial biofilm growth versus tissue integration on biomaterials with different wettabilities and a polymer-brush coating

    NARCIS (Netherlands)

    Subbiahdoss, Guruprakash; Grijpma, Dirk W.; van der Mei, Henny C.; Busscher, Henk J.; Kuijer, Roel


    Biomaterials-associated infections (BAI) constitute a major clinical problem and often necessitate implant replacement. In this study, the race for the surface between Staphylococcus epidermidis ATCC 35983 and U2OS osteosarcoma cells is studied on biomaterials with different wettabilities and on a p

  5. Injectable biomaterials for the treatment of stress urinary incontinence: their potential and pitfalls as urethral bulking agents.

    LENUS (Irish Health Repository)

    Davis, Niall F


    Injectable urethral bulking agents composed of synthetic and biological biomaterials are minimally invasive treatment options for stress urinary incontinence (SUI). The development of an ideal urethral bulking agent remains challenging because of clinical concerns over biocompatibility and durability. Herein, the mechanical and biological features of injectable urethral biomaterials are investigated, with particular emphasis on their future potential as primary and secondary treatment options for SUI. A literature search for English language publications using the two online databases was performed. Keywords included "stress urinary incontinence", "urethral bulking agent" and "injectable biomaterial". A total of 98 articles were analysed, of which 45 were suitable for review based on clinical relevance and importance of content. Injectable biomaterials are associated with a lower cure rate and fewer postoperative complications than open surgery for SUI. They are frequently reserved as secondary treatment options for patients unwilling or medically unfit to undergo surgery. Glutaraldehyde cross-linked bovine collagen remains the most commonly injected biomaterial and has a cure rate of up to 53 %. Important clinical features of an injectable biomaterial are durability, biocompatibility and ease of administration, but achieving these requirements is challenging. In carefully selected patients, injectable biomaterials are feasible alternatives to open surgical procedures as primary and secondary treatment options for SUI. In future, higher cure rates may be feasible as researchers investigate alternative biomaterials and more targeted injection techniques for treating SUI.

  6. Chaotic diagonal recurrent neural network

    Institute of Scientific and Technical Information of China (English)

    Wang Xing-Yuan; Zhang Yi


    We propose a novel neural network based on a diagonal recurrent neural network and chaos,and its structure andlearning algorithm are designed.The multilayer feedforward neural network,diagonal recurrent neural network,and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map.The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks.

  7. Mold-Based Application of Laser-Induced Periodic Surface Structures (LIPSS) on Biomaterials for Nanoscale Patterning. (United States)

    Hendrikson, Wim; Masman-Bakker, Wendy; van Bochove, Bas; Skolski, Johann; Eichstädt, Justus; Koopman, Bart; van Blitterswijk, Clemens; Grijpma, Dirk; Römer, Gert-Willem; Moroni, Lorenzo; Rouwkema, Jeroen


    Laser-induced periodic surface structures (LIPSS) are highly regular, but at the same time contain a certain level of disorder. The application of LIPSS is a promising method to functionalize biomaterials. However, the absorption of laser energy of most polymer biomaterials is insufficient for the direct application of LIPSS. Here, we report the application of LIPSS to relevant biomaterials using a two-step approach. First, LIPSS are fabricated on a stainless steel surface. Then, the structures are replicated onto biomaterials using the steel as a mold. Results show that LIPSS can be transferred successfully using this approach, and that human mesenchymal stromal cells respond to the transferred structures. With this approach, the range of biomaterials that can be supplied with LIPSS increases dramatically.

  8. Engineering biomaterial surfaces using nanoparticle assemblies: A new paradigm for modulating cell function (United States)

    Lipski, Anna Marie

    Silica nanoparticles (NP) were investigated as a surface modification medium and their impact on cell function was studied. This work has demonstrated that NP assemblies are suitable for the surface modification of both metal and polymer substrates. Additionally, important surface parameters, such as nano-roughness, charge, and chemistry, can be imparted in a predictable manner. More importantly, by varying the NP size, nano-roughness of a surface can be varied independent of chemistry. Two terminally differentiated mammalian cell types, bovine aortic endothelial cells (BAEC) and murine calvarial osteoblast-like cells (MC3T3-E1), were used to probe the effects of nano-topography on cell proliferation, metabolic activity, spreading, cytoskeletal F-actin alignment, and focal adhesion recruitment. Furthermore, the influence of nano-topography on cell migration was studied using BAEC and human fetal osteoblasts (hFOB). The results suggested that surface nano-rugosity affects cell behavior at various levels and that these effects are cell type specific; however, some clear trends were discerned with respect to F-actin alignment and cell migration. In particular, presentation of nano-features resulted in enhancement of cytoskeletal F-actin alignment along the long axis of the cells in comparison to unmodified glass. With respect to cell migration, increased nano-roughness resulted in decreased migration rates for both BAEC and hFOB. Finally, the potential of nano-rugosity as a mediator of cell differentiation was investigated by following the lineage specific differentiation of human marrow-derived mesenchymal progenitor cells (MPC) on NP-modified 316L stainless steel and titanium substrates. It was observed that NP modification enhanced the differentiation of MPC into an osteogenic lineage and that rugosity appeared to be the dominant factor in directing this differentiation. Thus, coatings composed of silica NPs presented a new paradigm that may lend themselves to

  9. Antibacterial Efficiency of Hydroxyapatite Biomaterials with Biodegradable Polylactic Acid and Polycaprolactone Polymers Saturated with Antibiotics / Bionoārdāmu Polimēru Saturošu Un Ar Antibiotiskajām Vielām Piesūcinātu Biomateriālu Antibakteriālās Efektivitātes Noteikšana

    Directory of Open Access Journals (Sweden)

    Kroiča Juta


    Full Text Available Infections continue to spread in all fields of medicine, and especially in the field of implant biomaterial surgery, and not only during the surgery, but also after surgery. Reducing the adhesion of bacteria could decrease the possibility of biomaterial-associated infections. Bacterial adhesion could be reduced by local antibiotic release from the biomaterial. In this in vitro study, hydroxyapatite biomaterials with antibiotics and biodegradable polymers were tested for their ability to reduce bacteria adhesion and biofilm development. This study examined the antibacterial efficiency of hydroxyapatite biomaterials with antibiotics and biodegradable polymers against Staphylococcus epidermidis and Pseudomonas aeruginosa. The study found that hydroxyapatite biomaterials with antibiotics and biodegradable polymers show longer antibacterial properties than hydroxyapatite biomaterials with antibiotics against both bacterial cultures. Therefore, the results of this study demonstrated that biomaterials that are coated with biodegradable polymers release antibiotics from biomaterial samples for a longer period of time and may be useful for reducing bacterial adhesion on orthopedic implants.

  10. Evolvable Neural Software System (United States)

    Curtis, Steven A.


    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  11. Sonic hedgehog elevates N-myc gene expression in neural stem cells. (United States)

    Liu, Dongsheng; Wang, Shouyu; Cui, Yan; Shen, Lun; Du, Yanping; Li, Guilin; Zhang, Bo; Wang, Renzhi


    Proliferation of neural stem cells is regulated by the secreted signaling molecule sonic hedgehog. In this study, neural stem cells were infected with recombinant adeno-associated virus expressing sonic hedgehog-N-enhanced green fluorescent protein. The results showed that overexpression of sonic hedgehog in neural stem cells induced the increased expression of Gli1 and N-myc, a target gene of sonic hedgehog. These findings suggest that N-myc is a direct downstream target of the sonic hedgehog signal pathway in neural stem cells. Sonic hedgehog and N-myc are important mediators of sonic hedgehog-induced proliferation of neural stem cells.

  12. Surfactant functionalization induces robust, differential adhesion of tumor cells and blood cells to charged nanotube-coated biomaterials under flow. (United States)

    Mitchell, Michael J; Castellanos, Carlos A; King, Michael R


    The metastatic spread of cancer cells from the primary tumor to distant sites leads to a poor prognosis in cancers originating from multiple organs. Increasing evidence has linked selectin-based adhesion between circulating tumor cells (CTCs) and endothelial cells of the microvasculature to metastatic dissemination, in a manner similar to leukocyte adhesion during inflammation. Functionalized biomaterial surfaces hold promise as a diagnostic tool to separate CTCs and potentially treat metastasis, utilizing antibody and selectin-mediated interactions for cell capture under flow. However, capture at high purity levels is challenged by the fact that CTCs and leukocytes both possess selectin ligands. Here, a straightforward technique to functionalize and alter the charge of naturally occurring halloysite nanotubes using surfactants is reported to induce robust, differential adhesion of tumor cells and blood cells to nanotube-coated surfaces under flow. Negatively charged sodium dodecanoate-functionalized nanotubes simultaneously enhanced tumor cell capture while negating leukocyte adhesion, both in the presence and absence of adhesion proteins, and can be utilized to isolate circulating tumor cells regardless of biomarker expression. Conversely, diminishing nanotube charge via functionalization with decyltrimethylammonium bromide both abolished tumor cell capture while promoting leukocyte adhesion.

  13. Xenopus reduced folate carrier regulates neural crest development epigenetically.

    Directory of Open Access Journals (Sweden)

    Jiejing Li

    Full Text Available Folic acid deficiency during pregnancy causes birth neurocristopathic malformations resulting from aberrant development of neural crest cells. The Reduced folate carrier (RFC is a membrane-bound receptor for facilitating transfer of reduced folate into the cells. RFC knockout mice are embryonic lethal and develop multiple malformations, including neurocristopathies. Here we show that XRFC is specifically expressed in neural crest tissues in Xenopus embryos and knockdown of XRFC by specific morpholino results in severe neurocristopathies. Inhibition of RFC blocked the expression of a series of neural crest marker genes while overexpression of RFC or injection of 5-methyltetrahydrofolate expanded the neural crest territories. In animal cap assays, knockdown of RFC dramatically reduced the mono- and trimethyl-Histone3-K4 levels and co-injection of the lysine methyltransferase hMLL1 largely rescued the XRFC morpholino phenotype. Our data revealed that the RFC mediated folate metabolic pathway likely potentiates neural crest gene expression through epigenetic modifications.

  14. Know Your Place: Neural Processing of Social Hierarchy in Humans (United States)

    Zink, Caroline F.; Tong, Yunxia; Chen, Qiang; Bassett, Danielle S.; Stein, Jason L.; Meyer-Lindenberg, Andreas


    Summary Social hierarchies guide behavior in many species, including humans, where status also has an enormous impact on motivation and health. However, little is known about the underlying neural representation of social hierarchies in humans. In the present study, we identify dissociable neural responses to perceived social rank using functional magnetic resonance imaging (fMRI) in an interactive simulated social context. In both stable and unstable social hierarchies, viewing a superior individual differentially engaged perceptual-attentional, saliency, and cognitive systems, notably dorsolateral prefrontal cortex. In the unstable hierarchy setting, additional regions were recruited related to emotional processing (amygdala), social cognition (medial prefrontal cortex), and behavioral readiness. Furthermore, social hierarchical consequences of performance were neurally dissociable and of comparable salience to monetary reward, providing a neural basis for the high motivational value of status. Our results identify neural mechanisms that may mediate the enormous influence of social status on human behavior and health. PMID:18439411

  15. Materiomics for Oral Disease Diagnostics and Personal Health Monitoring: Designer Biomaterials for the Next Generation Biomarkers. (United States)

    Zhang, Wenjun; Wang, Ming L; Khalili, Sammy; Cranford, Steven W


    We live in exciting times for a new generation of biomarkers being enabled by advances in the design and use of biomaterials for medical and clinical applications, from nano- to macro-materials, and protein to tissue. Key challenges arise, however, due to both scientific complexity and compatibility of the interface of biology and engineered materials. The linking of mechanisms across scales by using a materials science approach to provide structure-process-property relations characterizes the emerging field of 'materiomics,' which offers enormous promise to provide the hitherto missing tools for biomaterial development for clinical diagnostics and the next generation biomarker applications towards personal health monitoring. Put in other words, the emerging field of materiomics represents an essentially systematic approach to the investigation of biological material systems, integrating natural functions and processes with traditional materials science perspectives. Here we outline how materiomics provides a game-changing technology platform for disruptive innovation in biomaterial science to enable the design of tailored and functional biomaterials--particularly, the design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. Rigorous and complementary computational modeling and experimental techniques will provide an efficient means to develop new clinical technologies in silico, greatly accelerating the translation of materiomics-driven oral health diagnostics from concept to practice in the clinic.

  16. Opportunities for biomaterials : economic, environmental and policy aspects along their life cycle

    NARCIS (Netherlands)

    Hermann, B.G.


    Little was known at the start of these studies regarding the environmental impacts of bulk chemicals production from biomass and whether they could be produced economically. We have therefore analysed the entire life cycle of biomaterials: the production of bio-based chemicals, the application of bi

  17. [Engineered spider silk: the intelligent biomaterial of the future. Part I]. (United States)

    Florczak, Anna; Piekoś, Konrad; Kaźmierska, Katarzyna; Mackiewicz, Andrzej; Dams-Kozłowska, Hanna


    The unique properties of spider silk such as strength, extensibility, toughness, biocompatibility and biodegradability are the reasons for the recent development in silk biomaterial technology. For a long time scientific progress was impeded by limited access to spider silk. However, the development of the molecular biology strategy was a breaking point in synthetic spider silk protein design. The sequences of engineered spider silk are based on the consensus motives of the corresponding natural equivalents. Moreover, the engineered silk proteins may be modified in order to gain a new function. The strategy of the hybrid proteins constructed on the DNA level combines the sequence of engineered silk, which is responsible for the biomaterial structure, with the sequence of polypeptide which allows functionalization of the silk biomaterial. The functional domains may comprise receptor binding sites, enzymes, metal or sugar binding sites and others. Currently, advanced research is being conducted, which on the one hand focuses on establishing the particular silk structure and understanding the process of silk thread formation in nature. On the other hand, there are attempts to improve methods of engineered spider silk protein production. Due to acquired knowledge and recent progress in synthetic protein technology, the engineered silk will turn into intelligent biomaterial of the future, while its industrial production scale will trigger a biotechnological revolution.

  18. Responsive Biomaterials: Advances in Materials Based on Shape-Memory Polymers. (United States)

    Hardy, John G; Palma, Matteo; Wind, Shalom J; Biggs, Manus J


    Shape-memory polymers (SMPs) are morphologically responsive materials with potential for a variety of biomedical applications, particularly as devices for minimally invasive surgery and the delivery of therapeutics and cells for tissue engineering. A brief introduction to SMPs is followed by a discussion of the current progress toward the development of SMP-based biomaterials for clinically relevant biomedical applications.

  19. Generation and Assessment of Functional Biomaterial Scaffolds for Applications in Cardiovascular Tissue Engineering and Regenerative Medicine (United States)

    Hinderer, Svenja; Brauchle, Eva


    Current clinically applicable tissue and organ replacement therapies are limited in the field of cardiovascular regenerative medicine. The available options do not regenerate damaged tissues and organs, and, in the majority of the cases, show insufficient restoration of tissue function. To date, anticoagulant drug‐free heart valve replacements or growing valves for pediatric patients, hemocompatible and thrombus‐free vascular substitutes that are smaller than 6 mm, and stem cell‐recruiting delivery systems that induce myocardial regeneration are still only visions of researchers and medical professionals worldwide and far from being the standard of clinical treatment. The design of functional off‐the‐shelf biomaterials as well as automatable and up‐scalable biomaterial processing methods are the focus of current research endeavors and of great interest for fields of tissue engineering and regenerative medicine. Here, various approaches that aim to overcome the current limitations are reviewed, focusing on biomaterials design and generation methods for myocardium, heart valves, and blood vessels. Furthermore, novel contact‐ and marker‐free biomaterial and extracellular matrix assessment methods are highlighted. PMID:25778713

  20. Development of a hybrid scaffold with synthetic biomaterials and hydrogel using solid freeform fabrication technology

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Jin-Hyung; Park, Min; Park, Jaesung; Cho, Dong-Woo [Department of Mechanical Engineering, POSTECH (Korea, Republic of); Kim, Jong Young, E-mail: [Department of Mechanical Engineering, Andong National University (Korea, Republic of)


    Natural biomaterials such as hyaluronic acid, gelatin and collagen provide excellent environments for tissue regeneration. Furthermore, gel-state natural biomaterials are advantageous for encapsulating cells and growth factors. In cell printing technology, hydrogel which contains cells was printed directly to form three-dimensional (3D) structures for tissue or organ regeneration using various types of printers. However, maintaining the 3D shape of the printed structure, which is made only of the hydrogel, is very difficult due to its weak mechanical properties. In this study, we developed a hybrid scaffold consisting of synthetic biomaterials and natural hydrogel using a multi-head deposition system, which is useful in solid freeform fabrication technology. The hydrogel was intentionally infused into the space between the lines of a synthetic biomaterial-based scaffold. The cellular efficacy of the hybrid scaffold was validated using rat primary hepatocytes and a mouse pre-osteoblast MC3T3-E1 cell line. In addition, the collagen hydrogel, which encapsulates cells, was dispensed and the viability of the cells observed. We demonstrated superior effects of the hybrid scaffold on cell adhesion and proliferation and showed the high viability of dispensed cells.

  1. In Vitro Evaluation of Spider Silk Meshes as a Potential Biomaterial for Bladder Reconstruction

    NARCIS (Netherlands)

    Steins, A.; Dik, P.; Müller, W.H.; Vervoort, S.J.; Reimers, K.; Kubhier, J.W.; Vogt, P.M.; Apeldoorn, van A.A.; Coffer, P.J.; Schepers, K.


    Reconstruction of the bladder by means of both natural and synthetic materials remains a challenge due to severe adverse effects such as mechanical failure. Here we investigate the application of spider major ampullate gland-derived dragline silk from the Nephila edulis spider, a natural biomaterial

  2. Trends in surface engineering of biomaterials: atmospheric pressure plasma deposition of coatings for biomedical applications (United States)

    da Ponte, G.; Sardella, E.; Fanelli, F.; D'Agostino, R.; Favia, P.


    Cold plasma processes for surface engineering of biomaterials and biomedical devices are traditionally performed at low pressure; more and more, though, surface modification plasma processes at atmospheric pressure are also gaining popularity. This short review is aimed to list briefly atmospheric pressure plasma processes reported, in the last decade, for adapting the surface of materials to the best interactions with cells, bacteria and biomolecules.

  3. Time-related contact angle measurements with human plasma on biomaterial surfaces

    NARCIS (Netherlands)

    Rakhorst, G; Van der Mei, HC; Van Oeveren, W; Spijker, HT; Busscher, HJ


    Axisymmetric drop shape analysis by profile (ADSA-P) was used to assess in time contact angle changes of human plasma drops placed on four different biomaterials. Results were related with conventional blood compatibility measurements: albumin adsorption, fibrinogen adsorption and platelet adhesion.

  4. Biomaterial porosity determined by fractal dimensions, succolarity and lacunarity on microcomputed tomographic images

    Energy Technology Data Exchange (ETDEWEB)

    N' Diaye, Mambaye [LUNAM Université, GEROM Groupe Etudes Remodelage Osseux et bioMatériaux-LHEA, IRIS-IBS Institut de Biologie en Santé, CHU d' Angers, 49933 ANGERS Cedex (France); Degeratu, Cristinel [LUNAM Université, GEROM Groupe Etudes Remodelage Osseux et bioMatériaux-LHEA, IRIS-IBS Institut de Biologie en Santé, CHU d' Angers, 49933 ANGERS Cedex (France); University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Department of Bioresources and Polymer Science, Calea Victoriei 149, 010072, Sector 1, Bucharest (Romania); Bouler, Jean-Michel [Inserm UMR 791, LIOAD, University of Nantes, 44000 Nantes (France); Chappard, Daniel, E-mail: [LUNAM Université, GEROM Groupe Etudes Remodelage Osseux et bioMatériaux-LHEA, IRIS-IBS Institut de Biologie en Santé, CHU d' Angers, 49933 ANGERS Cedex (France)


    Porous structures are becoming more and more important in biology and material science because they help in reducing the density of the grafted material. For biomaterials, porosity also increases the accessibility of cells and vessels inside the grafted area. However, descriptors of porosity are scanty. We have used a series of biomaterials with different types of porosity (created by various porogens: fibers, beads …). Blocks were studied by microcomputed tomography for the measurement of 3D porosity. 2D sections were re-sliced to analyze the microarchitecture of the pores and were transferred to image analysis programs: star volumes, interconnectivity index, Minkowski–Bouligand and Kolmogorov fractal dimensions were determined. Lacunarity and succolarity, two recently described fractal dimensions, were also computed. These parameters provided a precise description of porosity and pores' characteristics. Non-linear relationships were found between several descriptors e.g. succolarity and star volume of the material. A linear correlation was found between lacunarity and succolarity. These techniques appear suitable in the study of biomaterials usable as bone substitutes. Highlights: ► Interconnected porosity is important in the development of bone substitutes. ► Porosity was evaluated by 2D and 3D morphometry on microCT images. ► Euclidean and fractal descriptors measure interconnectivity on 2D microCT images. ► Lacunarity and succolarity were evaluated on a series of porous biomaterials.

  5. Inhibition of the tissue reaction to a biodegradable biomaterial by monoclonal antibodies to IFN-gamma

    NARCIS (Netherlands)

    Khouw, IMSL; van Wachem, PB; de Leij, LFMH; van Luyn, MJA


    Biomaterials are increasingly used for clinical applications. However, loss of function may occur owing to tissue reactions, which are mainly caused by a variety of inflammatory reactions. Recently, we demonstrated that macrophages (MO) and T cells play key roles in these reactions. Since immunologi

  6. Antimicrobial biomaterials based on carbon nanotubes dispersed in poly(lactic-co-glycolic acid) (United States)

    Aslan, Seyma; Loebick, Codruta Zoican; Kang, Seoktae; Elimelech, Menachem; Pfefferle, Lisa D.; van Tassel, Paul R.


    Biomaterials that inactivate microbes are needed to eliminate medical device infections. We investigate here the antimicrobial nature of single-walled carbon nanotubes (SWNTs) incorporated within the biomedical polymer poly(lactic-co-glycolic acid) (PLGA). We find Escherichia coli and Staphylococcus epidermidis viability and metabolic activity to be significantly diminished in the presence of SWNT-PLGA, and to correlate with SWNT length and concentration (bacteria die within one hour on SWNT-PLGA versus 15-20% on pure PLGA. Shorter SWNTs are more toxic, possibly due to increased density of open tube ends. This study demonstrates the potential usefulness of SWNT-PLGA as an antimicrobial biomaterial.Biomaterials that inactivate microbes are needed to eliminate medical device infections. We investigate here the antimicrobial nature of single-walled carbon nanotubes (SWNTs) incorporated within the biomedical polymer poly(lactic-co-glycolic acid) (PLGA). We find Escherichia coli and Staphylococcus epidermidis viability and metabolic activity to be significantly diminished in the presence of SWNT-PLGA, and to correlate with SWNT length and concentration (bacteria die within one hour on SWNT-PLGA versus 15-20% on pure PLGA. Shorter SWNTs are more toxic, possibly due to increased density of open tube ends. This study demonstrates the potential usefulness of SWNT-PLGA as an antimicrobial biomaterial. Electronic supplementary information (ESI) available: Raman spectra before and after SWNT cutting via cyclodextrins, and sample images from viability and metabolic activity assays are included. See DOI: 10.1039/c0nr00329h

  7. Biomaterial-stem cell interactions and their impact on stem cell response

    NARCIS (Netherlands)

    Oziemlak-Schaap, Aneta M.; Kuhn, Philipp T.; van Kooten, Theo G.; van Rijn, Patrick


    In this review, current research in the field of biomaterial properties for directing stem cells are discussed and placed in a critical perspective. Regenerative medicine, in which stem cells play a crucial role, has become an interdisciplinary field between cell biology and materials science. New i

  8. Integrating dental anatomy and biomaterials: an innovative use of composite resin. (United States)

    Allen, Kenneth L; McAndrew, Maureen


    As part of the new integrated curriculum at the New York University College of Dentistry, a pilot program uses composite resins to teach dental anatomy. The Department of Biomaterials and Biomimetics, in conjunction with the Department of Cariology and Operative Dentistry, has created a teaching module to replicate the morphology of a central incisor through the manipulation and placement of a composite resin.


    NARCIS (Netherlands)



    The cytotoxicity of biomaterials can be tested in vitro using various culture systems. Liquid culture systems may detect cytotoxicity of a material either by culture of cells with extracts or with the material itself. In the latter instance, renewing the medium will remove possible released cytotoxi

  10. Biomaterials use in Mulago National Referral Hospital in Kampala, Uganda: Access and affordability. (United States)

    Bakwatanisa, Bosco; Enywaku, Alfred; Kiwanuka, Martin; Lamunu, Claire; Mbowa, Nicholas; Mukiibi, Denis; Namayega, Catherine; Ngabirano, Beryl; Ntambi, Henry; Reichert, William


    Students in Biomaterials BBE3102 at Makerere University in Kampala, Uganda were assigned semester long group projects in the first semester of the 2014-15 academic year to determine the biomaterials type and usage in Mulago National Referral Hospital, which is emblematic of large public hospitals across East Africa. Information gathering was conducted through student interviews with Mulago physicians because there were no archival records. The students divided themselves into seven project groups covering biomaterials use in the areas of wound closure, dental and oral surgery, cardiology, burn care, bone repair, ophthalmology and total joint replacement. As in the developed world, the majority of biomaterials used in Mulago are basic wound closure materials, dental materials, and bone fixation materials, all of which are comparatively inexpensive, easy to store, and readily available from either the government or local suppliers; however, there were significant issues with the implant supply chain, affordability, and patient compliance and follow-up in cases where specialty expertise and expensive implants were employed.

  11. Determination of optical properties in dental restorative biomaterials using the inverse-adding-doubling method (United States)

    Fernández-Oliveras, Alicia; Rubiño, Manuel; Pérez, María. M.


    Light propagation in biological media is characterized by the absorption coefficient, the scattering coefficient, the scattering phase function, the refractive index, and the surface conditions (roughness). By means of the inverse-adding-doubling (IAD) method, transmittance and reflectance measurements lead to the determination of the absorption coefficient and the reduced scattering coefficient. The additional measurement of the phase function performed by goniometry allows the separation of the reduced scattering coefficient into the scattering coefficient and the scattering anisotropy factor. The majority of techniques, such as the one utilized in this work, involve the use of integrating spheres to measure total transmission and reflection. We have employed an integrating sphere setup to measure the total transmittance and reflectance of dental biomaterials used in restorative dentistry. Dental biomaterials are meant to replace dental tissues, such as enamel and dentine, in irreversibly diseased teeth. In previous works we performed goniometric measurements in order to evaluate the scattering anisotropy factor for these kinds of materials. In the present work we have used the IAD method to combine the measurements performed using the integrating sphere setup with the results of the previous goniometric measurements. The aim was to optically characterize the dental biomaterials analyzed, since whole studies to assess the appropriate material properties are required in medical applications. In this context, complete optical characterizations play an important role in achieving the fulfillment of optimal quality and the final success of dental biomaterials used in restorative dentistry.

  12. In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials

    Directory of Open Access Journals (Sweden)

    Dai ZY


    Full Text Available Zhenyu Dai,1,2,* Yue Li,3,* Weizhong Lu,2,* Dianming Jiang,4 Hong Li,1 Yonggang Yan,1 Guoyu Lv,1 Aiping Yang1 1College of Physical Science and Technology, Sichuan University, Chengdu, 2Department of Orthopedics, Chongqing Hospital of Traditional Chinese Medicine, 3Department of Clinical Laboratory, the Second Affiliated Hospital, 4Department of Orthopedics, the First Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Objective: To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA complex biomaterials with muscle and bone tissue in an in vivo model.Methods: Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining.Results: HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that

  13. Folate receptors and neural tube closure. (United States)

    Saitsu, Hirotomo


    Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5-8/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1-kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1-kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.

  14. Transform method for laser speckle strain-rate measurements in biological tissues and biomaterials (United States)

    Kirkpatrick, Sean J.


    Laser speckle strain measurements in biological tissues and some synthetic biomaterials, such as translucent dental composites and ceramics, are often complicated by the physical properties of the materials. For example, speckles generated by illuminating soft biological tissue with laser light are subject to rapid decorrelation due to the Brownian movement of water and scattering particles in the tissues and to cellular motions. In addition, the penetration of the laser beam into the tissue or translucent biomaterial results in multiple scattering and a complete depolarization of the speckle field. This may complicate the evaluation of the strain field when a force is applied to the material because the speckle pattern shift is providing information from the surface of the material as well as from the bulk sample, where the strains may or may not be the same as on the surface. This paper presents a variation of a speckle processing scheme originally called the `Transform Method' for evaluating both surface and bulk strain rates and total strains in biological tissues and translucent biomaterials. The method is not a correlation-based technique, but instead relies upon 2D frequency transforms of time series of 1D speckle pattern records stacked into 2D arrays. The method is insensitive to speckle field depolarization and, compared to correlation-based techniques, is relatively insensitive to speckle decorrelation. Strain rates and total in-plane strains were measured in both hard (cortical bone) and soft (artery segments) biological tissues and in translucent biomaterials (dental ceramics). Potential applications to medical diagnostics and biomaterials science are also discussed.

  15. Strategies to balance covalent and non-covalent biomolecule attachment within collagen-GAG biomaterials. (United States)

    Pence, Jacquelyn C; Gonnerman, Emily A; Bailey, Ryan C; Harley, Brendan A C


    Strategies to integrate instructive biomolecular signals into a biomaterial are becoming increasingly complex and bioinspired. While a large majority of reports still use repeated treatments with soluble factors, this approach can be prohibitively costly and difficult to translate in vivo for applications where spatial control over signal presentation is necessary. Recent efforts have explored the use of covalent immobilization of biomolecules to the biomaterial, via both bulk (ubiquitous) as well as spatially-selective light-based crosslinking, as a means to both enhance stability and bioactivity. However, little is known about how processing conditions during immobilization impact the degree of unintended non-covalent interactions, or fouling, that takes place between the biomaterial and the biomolecule of interest. Here we demonstrate the impact of processing conditions for bulk carbodiimide (EDC) and photolithography-based benzophenone (BP) crosslinking on specific attachment vs. fouling of a model protein (Concanavalin A, ConA) within collagen-glycosaminoglycan (CG) scaffolds. Collagen source significantly impacts the selectivity of biomolecule immobilization. EDC crosslinking intensity and ligand concentration significantly impacted selective immobilization. For benzophenone photoimmobilization we observed that increased UV exposure time leads to increased ConA immobilization. Immobilization efficiency for both EDC and BP strategies was maximal at physiological pH. Increasing ligand concentration during immobilization process led to enhanced immobilization for EDC chemistry, no impact on BP immobilization, but significant increases in non-specific fouling. Given recent efforts to covalently immobilize biomolecules to a biomaterial surface to enhance bioactivity, improved understanding of the impact of crosslinking conditions on selective attachment versus non-specific fouling will inform the design of instructive biomaterials for applications across tissue

  16. Effects of bone morphogenetic protein-7 stimulation on osteoblasts cultured on different biomaterials. (United States)

    Açil, Yahya; Springer, Ingo N G; Broek, Vanessa; Terheyden, Hendrik; Jepsen, Søren


    The objective of the present study was to investigate the effects of an in vitro stimulation of human osteoblasts by recombinant human bone morphogenetic protein-7 (rhBMP-7) on the collagen types and the quantity of the collagen cross-links synthesized in a three-dimensional culture on various biomaterials for bone replacement. Trabecular bone chips were harvested from human iliac crests, and cell cultures were established at standard conditions. One hundred and fifty nanograms per milliliter of rhBMP-7 was added. For the second passage a cell scraper was used to bring the cells into suspension, and 100 microl osteoblasts (at a density of 3.3 x 10(5)) were transferred onto nine blocks of either Bio-Oss, Tutoplast, or PepGen p-15. Blocks incubated with cells that were not treated with rhBMP-7 served as controls. Cell colonization of the biomaterials was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) after a period of 2, 4, and 6 weeks. Throughout the experiment medium, supernatants were collected and collagen was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Finally, the collagen cross-link residues hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) were quantified by HPLC. Within 4 weeks the cells became confluent on all of the studied biomaterials. All samples synthesized bone specific LP and collagen type I. However, in rhBMP-7-stimulated samples, the amount of HP and LP found was increased by 45% compared to non-stimulated samples. Cell proliferation and collagen synthesis was similar on the different biomaterials, but was consistently reduced in specimen not stimulated with rhBMP-7. In vitro stimulation of osteoblasts on Bio-Oss, Tutoplast, or PepGen p-15 with rhBMP-7 and subsequent transplantation of the constructs might lead to an enhanced osseointegration of the biomaterials in vivo.

  17. A neural flow estimator

    DEFF Research Database (Denmark)

    Jørgensen, Ivan Harald Holger; Bogason, Gudmundur; Bruun, Erik


    This paper proposes a new way to estimate the flow in a micromechanical flow channel. A neural network is used to estimate the delay of random temperature fluctuations induced in a fluid. The design and implementation of a hardware efficient neural flow estimator is described. The system...... is implemented using switched-current technique and is capable of estimating flow in the μl/s range. The neural estimator is built around a multiplierless neural network, containing 96 synaptic weights which are updated using the LMS1-algorithm. An experimental chip has been designed that operates at 5 V...

  18. Neural Systems Laboratory (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  19. Scaffolds for 3D in vitro culture of neural lineage cells. (United States)

    Murphy, Ashley R; Laslett, Andrew; O'Brien, Carmel M; Cameron, Neil R


    Understanding how neurodegenerative disorders develop is not only a key challenge for researchers but also for the wider society, given the rapidly aging populations in developed countries. Advances in this field require new tools with which to recreate neural tissue in vitro and produce realistic disease models. This in turn requires robust and reliable systems for performing 3D in vitro culture of neural lineage cells. This review provides a state of the art update on three-dimensional culture systems for in vitro development of neural tissue, employing a wide range of scaffold types including hydrogels, solid porous polymers, fibrous materials and decellularised tissues as well as microfluidic devices and lab-on-a-chip systems. To provide some context with in vivo development of the central nervous system (CNS), we also provide a brief overview of the neural stem cell niche, neural development and neural differentiation in vitro. We conclude with a discussion of future directions for this exciting and important field of biomaterials research.

  20. Neural Networks: Implementations and Applications

    NARCIS (Netherlands)

    Vonk, E.; Veelenturf, L.P.J.; Jain, L.C.


    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  1. What Are Neural Tube Defects? (United States)

    ... NICHD Research Information Clinical Trials Resources and Publications Neural Tube Defects (NTDs): Condition Information Skip sharing on social media links Share this: Page Content What are neural tube defects? Neural (pronounced NOOR-uhl ) tube defects are ...

  2. Critical Branching Neural Networks (United States)

    Kello, Christopher T.


    It is now well-established that intrinsic variations in human neural and behavioral activity tend to exhibit scaling laws in their fluctuations and distributions. The meaning of these scaling laws is an ongoing matter of debate between isolable causes versus pervasive causes. A spiking neural network model is presented that self-tunes to critical…

  3. Kunstige neurale net

    DEFF Research Database (Denmark)

    Hørning, Annette


    Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse.......Artiklen beskæftiger sig med muligheden for at anvende kunstige neurale net i forbindelse med datamatisk procession af naturligt sprog, specielt automatisk talegenkendelse....

  4. Is neural Darwinism Darwinism? (United States)

    van Belle, T


    Neural Darwinism is a theory of cognition developed by Gerald Edelman along with George Reeke and Olaf Sporns at Rockefeller University. As its name suggests, neural Darwinism is modeled after biological Darwinism, and its authors assert that the two processes are strongly analogous. both operate on variation in a population, amplifying the more adaptive individuals. However, from a computational perspective, neural Darwinism is quite different from other models of natural selection, such as genetic algorithms. The individuals of neural Darwinism do not replicate, thus robbing the process of the capacity to explore new solutions over time and ultimately reducing it to a random search. Because neural Darwinism does not have the computational power of a truly Darwinian process, it is misleading to label it as such. to illustrate this disparity in adaptive power, one of Edelman's early computer experiments, Darwin I, is revisited, and it is shown that adding replication greatly improves the adaptive power of the system.

  5. The Promotion of Human Neural Stem Cells Adhesion Using Bioinspired Poly(norepinephrine Nanoscale Coating

    Directory of Open Access Journals (Sweden)

    Minah Park


    Full Text Available The establishment of versatile biomaterial interfaces that can facilitate cellular adhesion is crucial for elucidating the cellular processes that occur on biomaterial surfaces. Furthermore, biomaterial interfaces can provide physical or chemical cues that are capable of stimulating cellular behaviors by regulating intracellular signaling cascades. Herein, a method of creating a biomimetic functional biointerface was introduced to enhance human neural stem cell (hNSC adhesion. The hNSC-compatible biointerface was prepared by the oxidative polymerization of the neurotransmitter norepinephrine, which generates a nanoscale organic thin layer, termed poly(norepinephrine (pNE. Due to its adhesive property, pNE resulted in an adherent layer on various substrates, and pNE-coated biointerfaces provided a highly favorable microenvironment for hNSCs, with no observed cytotoxicity. Only a 2-hour incubation of hNSCs was required to firmly attach the stem cells, regardless of the type of substrate. Importantly, the adhesive properties of pNE interfaces led to micropatterns of cellular attachment, thereby demonstrating the ability of the interface to organize the stem cells. This highly facile surface-modification method using a biomimetic pNE thin layer can be applied to a number of suitable materials that were previously not compatible with hNSC technology.

  6. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial

    DEFF Research Database (Denmark)

    Raina, D B; Gupta, A; Petersen, M M;


    OBJECTIVES: We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth...... factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. MATERIALS AND METHODS: We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra...... microscopy. RESULTS: C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (sd) 0.8) and BMP-7 (50.6 ng/mg, sd 2.2). In vitro...

  7. Biocompatibility of helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials in a rabbit corneal model. (United States)

    Wang, Liqiang; Ma, Ruijue; Du, Gaiping; Guo, Huiling; Huang, Yifei


    Silk proteins represent a unique choice in the selection of biomaterials that can be used for corneal tissue engineering and regenerative medical applications. We implanted helicoidal multilamellar arginine-glycine-aspartic acid-functionalized silk biomaterials into the corneal stroma of rabbits, and evaluated its biocompatibility. The corneal tissue was examined after routine hematoxylin-eosin staining, immunofluorescence for collagen I and III, and fibronectin, and scanning electron microscopy. The silk films maintained their integrity and transparency over the 180-day experimental period without causing immunogenic and neovascular responses or degradation of the rabbit corneal stroma. Collagen I increased, whereas Collagen III and fibronectin initially increased and then gradually decreased. The extracellular matrix deposited on the surface of the silk films, tightly adhered to the biomaterial. We have shown this kind of silk film graft has suitable biocompatibility with the corneal stroma and is an initial step for clinical trials to evaluate this material as a transplant biomaterial for keratoplasty tissue constructs.

  8. Supracolloidal Assemblies as Sacrificial Templates for Porous Silk-Based Biomaterials

    Directory of Open Access Journals (Sweden)

    John G. Hardy


    Full Text Available Tissues in the body are hierarchically structured composite materials with tissue-specific properties. Urea self-assembles via hydrogen bonding interactions into crystalline supracolloidal assemblies that can be used to impart macroscopic pores to polymer-based tissue scaffolds. In this communication, we explain the solvent interactions governing the solubility of urea and thereby the scope of compatible polymers. We also highlight the role of solvent interactions on the morphology of the resulting supracolloidal crystals. We elucidate the role of polymer-urea interactions on the morphology of the pores in the resulting biomaterials. Finally, we demonstrate that it is possible to use our urea templating methodology to prepare Bombyx mori silk protein-based biomaterials with pores that human dermal fibroblasts respond to by aligning with the long axis of the pores. This methodology has potential for application in a variety of different tissue engineering niches in which cell alignment is observed, including skin, bone, muscle and nerve.

  9. Spider silk as a load bearing biomaterial: tailoring mechanical properties via structural modifications (United States)

    Brown, Cameron P.; Rosei, Federico; Traversa, Enrico; Licoccia, Silvia


    Spider silk shows great potential as a biomaterial: in addition to biocompatibility and biodegradability, its strength and toughness are greater than native biological fibres (e.g. collagen), with toughness exceeding that of synthetic fibres (e.g. nylon). Although the ultimate tensile strength and toughness at failure are unlikely to be limiting factors, its yield strain of 2% is insufficient, particularly for biomedical application because of the inability to mimic the complex ultrastructure of natural tissues with current tissue engineering approaches. To harness the full potential of spider silk as a biomaterial, it is therefore necessary to increase its yield strain. In this paper, we discuss the means by which the mechanical properties of spider silk, particularly the yield strain, can be optimized through structural modifications.

  10. Biological Evaluation of ChuangYuLing Dressing-A Multifunctional Medicine Carrying Biomaterial

    Institute of Scientific and Technical Information of China (English)

    PENG Rui; ZHENG Qixin; HAO Jie; ZOU Yang; CHENG Jie


    The safety of Chuangyuling (CYL) dressing-a multifunctional medicine carrying biomaterial was evaluated in order to provide foundation for the application of CYL as material used in the wound healing. The traditional Chinese medicine (TCM) extract solution was compounded with scaffolds (gelatin and Bletilla hyacinthine gum), and then frozen and dried to form spongy and porous material CYL. According to the standard of biological evaluation of medical devices that was instituted by the ministry of health of China[1] , the biological evaluation of CYL dressing was conducted. The results showed that all the contents of biological evaluation test consisting of acute toxicity, skin irritation, sensitization and cytotoxicity met the requirement of standards. It was concluded that the biomaterial carrying TCM (CYL dressing) is safe for application of wound healing.

  11. Injectable biomaterials: a perspective on the next wave of injectable therapeutics. (United States)

    Spector, Myron; Lim, Teck Chuan


    We are experiencing a new wave of injectable therapeutics (namely/injectable biomaterials) to complement injectable drugs and injectable biologics, and to serve as the basis for injectable combinatorial therapeutics. Injectable biomaterials contribute to the treatment of the fluid-filled defects which often result from disease and injury, by providing the missing physical framework (i.e. the stroma). However, while injectable matrices may be necessary for the successful treatment of certain lesions, they will not likely be sufficient. Chemoattractants for select endogenous cells, or cells themselves, may need to be incorporated into the matrix prior to its injection to ensure the necessary cellular repopulation of the cavitary defect. These agents and others (drugs and biologics) delivered by the matrix represent the new category of injectable combinatorial therapeutics.

  12. The potential contribution to climate change mitigation from temporary carbon storage in biomaterials

    DEFF Research Database (Denmark)

    Jørgensen, Susanne Vedel; Hauschild, Michael Zwicky; Nielsen, Per H.


    contributes with negative CTP values, which means mitigation. The longer the duration of the storage, the larger the mitigation potential.Temporary carbon storage in biomaterials has a potential for contributing to avoid or postpone the crossing of a climatic target level of 450 ppm CO2e, depending on GHG...... concentration development scenario. The potential mitigation value depends on the timing of sequestration and re-emission of CO2. The suggested CTP approach enables inclusion of the potential benefit from temporary carbon storage in the environmental profile of biomaterials. This should be seen as supplement...... value of temporary carbon storage in terms of climate change mitigation has been widely discussed, this has not yet been directly coupled to avoiding climatic target levels representing predicted climatic tipping points. This paper provides recommendations on how to model temporary carbon storage...

  13. Differences in the removal mechanisms of Undaria pinnatifida and Phragmites australis as biomaterials for lead removal. (United States)

    Soto-Rios, Paula Cecilia; Nakano, Kazunori; Leon-Romero, Marco; Aikawa, Yoshio; Arai, Shigeyuki; Nishimura, Osamu


    This study offers the opportunity to utilize Undaria pinnatifida and Phragmites australis to remove lead from water in permeable reactive barrier (PRB) technology. Its efficacy was tested using batch experiments and PRB column systems. From the batch experiment results, a higher adsorption capacity was observed for Undaria pinnatifida. Nevertheless, Phragmites australis in the column system efficiently removed lead and the breakthrough occurred at the same time for both biomaterials. To dissipate this difference, a sequential extraction for metal speciation analysis was used for both columns. The results have shown that each biomaterial has a dominant mechanism. Phragmites australis removed lead by physical adsorption, whereas Undaria pinnatifida showed a higher tendency to bind lead due to organic matter, primary and secondary minerals.

  14. Biomaterials-based electronics: polymers and interfaces for biology and medicine. (United States)

    Muskovich, Meredith; Bettinger, Christopher J


    Advanced polymeric biomaterials continue to serve as a cornerstone for new medical technologies and therapies. The vast majority of these materials, both natural and synthetic, interact with biological matter in the absence of direct electronic communication. However, biological systems have evolved to synthesize and utilize naturally-derived materials for the generation and modulation of electrical potentials, voltage gradients, and ion flows. Bioelectric phenomena can be translated into potent signaling cues for intra- and inter-cellular communication. These cues can serve as a gateway to link synthetic devices with biological systems. This progress report will provide an update on advances in the application of electronically active biomaterials for use in organic electronics and bio-interfaces. Specific focus will be granted to covering technologies where natural and synthetic biological materials serve as integral components such as thin film electronics, in vitro cell culture models, and implantable medical devices. Future perspectives and emerging challenges will also be highlighted.

  15. Long thermal interactions of PAW with normal tooth structure and different dental biomaterials (United States)

    Bostǎnaru, Andra-Cristina; Hnatiuc, Eugen; Roşca, Irina; Vasiliu, Ana Lavinia; Doroftei, Mirela; Ursu, Laura; Ailincǎi, Luminiţa Iuliana; Nǎstasǎ, Valentin; Mareş, Mihai


    Plasma activated water (PAW) has been widely considered to be an effective method for decontamination. Recently, numerous studies report that plasma-activated water (PAW) also has antibacterial ability to prevent or treat dental caries and periodontal related diseases. In this context, this study presents the first report to evaluate the plasma activated water effect on vital teeth enamel and different dental biomaterials. In this context, this study presents the first report to evaluate long thermal interactions of plasma activated water effect on vital teeth enamel and different dental biomaterials without organic substrate. The results suggest that the long-thermal of treatment with PAW of enamel without organic substrate can dissolve the apatite crystallites which are highly organized hierarchical structures.

  16. Biological issues in materials science and engineering: Interdisciplinarity and the bio-materials paradigm (United States)

    Murr, L. E.


    Biological systems and processes have had, and continue to have, important implications and applications in materials extraction, processing, and performance. This paper illustrates some interdisciplinary, biological issues in materials science and engineering. These include metal extraction involving bacterial catalysis, galvanic couples, bacterial-assisted corrosion and degradation of materials, biosorption and bioremediation of toxic and other heavy metals, metal and material implants and prostheses and related dental and medical biomaterials developments and applications, nanomaterials health benefits and toxicity issue, and biomimetics and biologically inspired materials developments. These and other examples provide compelling evidence and arguments for emphasizing biological sicences in materials science and engineering curricula and the implementation of a bio-materials paradigm to facilitate the emergence of innovative interdisciplinarity involving the biological sciences and materials sciences and engineering.

  17. Obtaining and characterization of chitosan biocomposites / HAP for application as biomaterial; Obtencao e caracterizacao de biocomposito quitosana/hidroxiapatita para aplicacao como biomaterial

    Energy Technology Data Exchange (ETDEWEB)

    Leal, R.C.A.; Nascimento, I.V.S.R.; Fook, M.V.L.; Furtado, G.T.F.S., E-mail: [Universidade Federal de Campina Grande (UFCG), PB (Brazil). Departamento de Engenharia de Materiais


    The hydroxyapatite is one of the most biocompatible materials known by encouraging bone growth. However, the main drawback it is the poor mechanical strength. A method to overcome this problem is the addition of the biopolymer chitosan, suitable for applications as biomaterials. In this study was obtained a hydroxyapatite - chitosan biocomposites for application as a biomaterial. In the FTIR analysis it was identified characteristic bands of hydroxyapatite and a possible overlap of the amino group of chitosan by carbonate. XRD analysis showed that there was no change in the profile of HA after chitosan incorporation. In SEM analysis of the biocomposites HA / chitosan, it is observed that there wasn't a complete dispersion of HA particles in the chitosan. In the image of calcined biocomposite, it was found that after heat treatment at 900 ° C chitosan was eliminated, resulting in a porous material. The analysis has shown that the presence of chitosan did not cause significant changes in the phase of hydroxyapatite. (author)

  18. Dynamics of neural cryptography. (United States)

    Ruttor, Andreas; Kinzel, Wolfgang; Kanter, Ido


    Synchronization of neural networks has been used for public channel protocols in cryptography. In the case of tree parity machines the dynamics of both bidirectional synchronization and unidirectional learning is driven by attractive and repulsive stochastic forces. Thus it can be described well by a random walk model for the overlap between participating neural networks. For that purpose transition probabilities and scaling laws for the step sizes are derived analytically. Both these calculations as well as numerical simulations show that bidirectional interaction leads to full synchronization on average. In contrast, successful learning is only possible by means of fluctuations. Consequently, synchronization is much faster than learning, which is essential for the security of the neural key-exchange protocol. However, this qualitative difference between bidirectional and unidirectional interaction vanishes if tree parity machines with more than three hidden units are used, so that those neural networks are not suitable for neural cryptography. In addition, the effective number of keys which can be generated by the neural key-exchange protocol is calculated using the entropy of the weight distribution. As this quantity increases exponentially with the system size, brute-force attacks on neural cryptography can easily be made unfeasible.

  19. Neural correlates underlying true and false associative memories. (United States)

    Dennis, Nancy A; Johnson, Christina E; Peterson, Kristina M


    Despite the fact that associative memory studies produce a large number of false memories, neuroimaging analyses utilizing this paradigm typically focus only on neural activity mediating successful retrieval. The current study sought to expand on this prior research by examining the neural basis of both true and false associative memories. Though associative false memories are substantially different than those found in semantic or perceptual false memory paradigms, results suggest that associative false memories are mediated by similar neural mechanisms. Specifically, we found increased frontal activity that likely represents enhanced monitoring and evaluation compared to that needed for true memories and correct rejections. Results also indicated that true, and not false associative memories, are mediated by neural activity in the MTL, specifically the hippocampus. Finally, while activity in early visual cortex distinguished true from false memories, a lack of neural differences between hits and correct rejections failed to support previous findings suggesting that activity in early visual cortex represents sensory reactivation of encoding-related processing.

  20. Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load-Bearing and Electroactive Tissues

    DEFF Research Database (Denmark)

    Mehrali, Mehdi; Thakur, Ashish; Pennisi, Christian Pablo


    , mechanical, and electrical properties. Here, recent advances in the fabrication and application of nanocomposite hydrogels in tissue engineering applications are described, with specific attention toward skeletal and electroactive tissues, such as cardiac, nerve, bone, cartilage, and skeletal muscle......Given their highly porous nature and excellent water retention, hydrogel-based biomaterials can mimic critical properties of the native cellular environment. However, their potential to emulate the electromechanical milieu of native tissues or conform well with the curved topology of human organs...