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PEGylation fibrinogen

Laurent Leclercq, Michel Vert
A previous investigation suggested that a surface bearing a rinsing-resistant depot (nanocoating) of albumin is more protein-repulsive than the same surface physically pegylated by a poly(D,L-lactic acid)-poly(ethylene oxide) diblock copolymer. To complement the study, Optical Waveguide Lightmode Spectroscopy was used to compare the mass and the thickness of protein depots from different systems, namely albumin alone at different concentrations, a mixture of albumin + fibrinogen + γ-globulin at their physiological concentrations, and sheep serum...
February 2017: Journal of Biomaterials Science. Polymer Edition
Laurence Rozen, Denis Noubouossie, Laurence Dedeken, Sophie Huybrechts, Phu Quoc Lê, Alina Ferster, Anne Demulder
BACKGROUND: Asparaginase (Asp) and corticosteroid (CS) treatment in patients with acute lymphoblastic leukaemia (ALL) is associated with an increased risk of thrombotic events. OBJECTIVE: Characterization of global haemostatic phenotypes of patients with ALL during Asp therapy. PROCEDURE: Thrombin generation (TG) was monitored in platelet-poor plasma of 56 children treated for a B lineage ALL (36 with native, 20 with PEG Asp) using 1 pM tissue factor and 4 μM phospholipids, with and without thrombomodulin...
February 2017: Pediatric Blood & Cancer
Shunsuke Tomita, Osamu Niwa, Ryoji Kurita
A novel strategy for construction of cross-reactive enzyme-based sensors have been developed based on chemical modification of lysine ε-NH3(+) groups in β-galactosidase (β-Gal) from Aspergillus oryzae with various acid anhydrides. Modification of lysine side chains markedly altered the kinetic parameters of β-Gal (KM and kcat), whereas catalytic activity remained and the tertiary structure was maintained for all modified β-Gals. The addition of cationic PEGylated polymers to reactive solutions caused the formation of polyion complexes (PICs) with marked inhibition of the modified β-Gal activity...
September 20, 2016: Analytical Chemistry
Michael Desborough, Lise J Estcourt, Carolyn Doree, Marialena Trivella, Sally Hopewell, Simon J Stanworth, Michael F Murphy
BACKGROUND: Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. OBJECTIVES: To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding...
August 22, 2016: Cochrane Database of Systematic Reviews
Irina I Vlasova, Elena V Mikhalchik, Nikolay A Barinov, Valeria A Kostevich, Natalia V Smolina, Dmitry V Klinov, Alexey V Sokolov
Proteins adsorbed on a surface may affect the interaction of this surface with cells. Here, we studied the binding of human serum albumin (HSA), fibrinogen (FBG) and immunoglobulin G (IgG) to PEGylated single-walled carbon nanotubes (PEG-SWCNTs) and evaluated the impact of PEG-SWCNT treated by these proteins on neutrophils in whole blood samples. Measurements of adsorption parameters revealed tight binding of proteins to PEG-SWCNTs. AFM was employed to directly observe protein binding to sidewalls of PEG-SWCNTs...
August 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Débora da-Silva-Freitas, Johara Boldrini-França, Eliane Candiani Arantes
PEGylation is considered a successful technique to enhance the therapeutic and biotechnological potentials of peptides, proteins, toxins and drugs. The conjugation of polyethylene glycol (PEG) increases the size and molecular weight of conjugated molecule and improves its pharmacokinetics and pharmacodinamics by increasing water solubility, protecting from enzymatic degradation, reducing renal clearance and limiting immunogenic and antigenic reactions. These features are very useful for therapeutic proteins, since PEGylated proteins exhibit high stability and very low immunogenicity, ensuring a sustained clinical response with minimal dose and less frequent administration...
2015: Protein and Peptide Letters
Beatriz Pelaz, Pablo del Pino, Pauline Maffre, Raimo Hartmann, Marta Gallego, Sara Rivera-Fernández, Jesus M de la Fuente, G Ulrich Nienhaus, Wolfgang J Parak
Here we have investigated the effect of enshrouding polymer-coated nanoparticles (NPs) with polyethylene glycol (PEG) on the adsorption of proteins and uptake by cultured cells. PEG was covalently linked to the polymer surface to the maximal grafting density achievable under our experimental conditions. Changes in the effective hydrodynamic radius of the NPs upon adsorption of human serum albumin (HSA) and fibrinogen (FIB) were measured in situ using fluorescence correlation spectroscopy. For NPs without a PEG shell, a thickness increase of around 3 nm, corresponding to HSA monolayer adsorption, was measured at high HSA concentration...
July 28, 2015: ACS Nano
Kazuaki Taguchi, Mai Hashimoto, Shigeru Ogaki, Hiroshi Watanabe, Shinji Takeoka, Yasuo Ikeda, Makoto Handa, Masaki Otagiri, Toru Maruyama
Adenosine diphosphate (ADP)-encapsulated liposomes coated with a fibrinogen γ-chain dodecapeptide [H12 (dodecapeptide ((400) HHLGGAKQAGDV(411) ))-(ADP)-liposome] is a synthetic platelet substitute, in which the surface is covered with polyethylene glycol (PEG). It has been reported that repeated injections of PEGylated liposomes induce an accelerated blood clearance (ABC) phenomenon, which involves a loss in the long-circulation half-life of the material when administered repeatedly to the same animals. The objective of this study was to determine whether the ABC phenomenon was induced by repeated injections of H12-(ADP)-liposome in healthy and anticancer drug-induced thrombocytopenia model rats...
September 2015: Journal of Pharmaceutical Sciences
Bae Hoon Lee, Myung Hee Kim, Jae Ho Lee, Dror Seliktar, Nam-Joon Cho, Lay Poh Tan
Physical cues, such as cell microenvironment stiffness, are known to be important factors in modulating cellular behaviors such as differentiation, viability, and proliferation. Apart from being able to trigger these effects, mechanical stiffness tuning is a very convenient approach that could be implemented readily into smart scaffold designs. In this study, fibrinogen-modified poly(ethylene glycol)-diacrylate (PEG-DA) based hydrogels with tunable mechanical properties were synthesized and applied to control the spheroid formation and liver-like function of encapsulated Huh7...
2015: PloS One
Laura R Geuss, Alicia C B Allen, Divya Ramamoorthy, Laura J Suggs
Successful cellular cardiomyoplasty is dependent on biocompatible materials that can retain the cells in the myocardium in order to promote host tissue repair following myocardial infarction. A variety of methods have been explored for incorporating a cell-seeded matrix into the heart, the most popular options being direct application of an injectable system or surgical implantation of a patch. Fibrin-based gels are suitable for either of these approaches, as they are biocompatible and have mechanical properties that can be tailored by adjusting the initial fibrinogen concentration...
July 2015: Biotechnology and Bioengineering
Eunna Chung, Julie A Rytlewski, Arjun G Merchant, Kabir S Dhada, Evan W Lewis, Laura J Suggs
Engineered three-dimensional biomaterials are known to affect the regenerative capacity of stem cells. The extent to which these materials can modify cellular activities is still poorly understood, particularly for adipose-derived stem cells (ASCs). This study evaluates PEGylated fibrin (P-fibrin) gels as an ASC-carrying scaffold for encouraging local angiogenesis by comparing with two commonly used hydrogels (i.e., collagen and fibrin) in the tissue-engineering field. Human ASCs in P-fibrin were compared to cultures in collagen and fibrin under basic growth media without any additional soluble factors...
April 2015: Acta Biomaterialia
Mariana B Oliveira, Olga Kossover, João F Mano, Dror Seliktar
A new methodology is reported for the continuous, solvent- and oil-free production of photopolymerizable microparticles containing encapsulated human dermal fibroblasts. A precursor solution of cells in photoreactive poly(ethylene glycol) (PEG)-fibrinogen (PF) polymer was transported through a transparent injector exposed to light irradiation before being atomized in a jet-in-air nozzle. Shear rheometry data revealed the crosslinking kinetics of the PF/cell solution, which was then used to determine the amount of irradiation required to partially polymerize the mixture just prior to atomization...
February 2015: Acta Biomaterialia
Iris Mironi-Harpaz, Alexandra Berdichevski, Dror Seliktar
Hydrogels are one of the most versatile biomaterials in use for tissue engineering and regenerative medicine. They are assembled from either natural or synthetic polymers, and their high water content gives these materials practical advantages in numerous biomedical applications. Semisynthetic hydrogels, such as those that combine synthetic and biological building blocks, have the added advantage of controlled bioactivity and material properties. In myocardial regeneration, injectable hydrogels premised on a semisynthetic design are advantageous both as bioactive bulking agents and as a delivery vehicle for controlled release of bioactive factors and/or cardiomyocytes...
2014: Methods in Molecular Biology
Yan-Wen Chen, Yung Chang, Rong-Ho Lee, Wen-Tyng Li, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Ging-Ho Hsiue
A PEGylated 96-well polystyrene (PS) microplate was first introduced for applications in high-throughput screening for selective blood typing to minimize the risks in blood transfusions. Herein, we present a hemocompatible PS 96-well microplate with adjustable PEGylated hyperbranch brush coverage prepared by ozone pretreated activation and thermally induced surface PEGylation. The grafting properties, hydration capacity, and blood compatibility of the PEGylated hyperbrush immobilized PS surfaces in human blood were illustrated by the combined chemical and physical properties of the surface, and the dependence of the specific absorption of human plasma fibrinogen onto the PEGylated surfaces on the grafting density was analyzed by monoclonal antibodies...
August 5, 2014: Langmuir: the ACS Journal of Surfaces and Colloids
Tarek Saadi, Omri Nayshool, Julie Carmel, Arie Ariche, Zakhar Bramnik, Iris Mironi-Harpaz, Dror Seliktar, Yaacov Baruch
INTRODUCTION: The liver is the natural microenvironment for hepatocytes transplantation but unfortunately engraftment efficiency is low. Cell-laden microhydrogels made of fibrinogen attached to poly(ethylene glycol) (PEG)-diacrylate side chains, were used as a cell carrier, for intravascular transplantation. This approach may reduce shear stress and immediate immunological pressure after intravascular transplantation and provide biomatrix for environmental support. AIMS: In vitro assessment of HuH-7 viability and function after polymerization within PEGylated fibrinogen-hydrogel...
November 2014: Tissue Engineering. Part A
Abdul Jalil Rufaihah, Srirangam Ramanujam Vaibavi, Marian Plotkin, Jiayi Shen, Venkateswaran Nithya, Jing Wang, Dror Seliktar, Theodoros Kofidis
Most tissue engineering therapies require biomaterials that are able to induce an angiogenic response to support tissue regeneration. In addition angiogenic growth factor signaling plays an essential role in controlling the process of angiogenesis and matrices have the potential of regulating the concentration of growth factors within the cellular microenvironment. Here we demonstrated myocardial protection and improved post-infarct vascularization of the infarcted hearts using a biosynthetic injectable hydrogel consisting of polyethylene glycol and fibrinogen (PEG-fibrinogen) loaded with vascular endothelial growth factor-A (VEGF-A)...
November 2013: Biomaterials
Laurent Leclercq, Enrico Modena, Michel Vert
In literature, contacts between pegylated compounds and blood proteins are generally discussed in terms of excluded volume-related repulsions although adsorption and compatibility have been reported for some of these proteins occasionally. The major problem to investigate the behavior of blood in contact with pegylated surfaces is the complexity of the medium and especially the presence of albumin in large excess. In a model approach, optical waveguide lightmode spectroscopy (OWLS) was used to monitor the fate of albumin, fibrinogen, and γ-globulins at physiological concentrations in pH = 7...
2013: Journal of Biomaterials Science. Polymer Edition
Aida Saray, Rusmir Mesihović, Zora Vukobrat-Bijedić, Srđan Gornjaković, Nenad Vanis, Amila Mehmedović, Vedad Papović, Sanjin Glavaš
Previous studies have reported reduced synthesis of various hemostatic factors in patients with chronic liver disease. Whether changes in plasma levels of these proteins reflect recovered liver synthetic function following virological eradication therapy has not been approved yet. The aim of the study was to determine the impact of sustained viral suppression achieved with pegylated interferon alpha and ribavirin on hemostatic parameters including natural anticoagulants in patients with chronic hepatitis C...
May 2013: Bosnian Journal of Basic Medical Sciences
Shahriar Absar, Kamrun Nahar, Young Min Kwon, Fakhrul Ahsan
PURPOSE: To test the hypothesis that thrombus-specific tissue plasminogen activator (tPA)-loaded nanocarriers enhance thrombolytic efficacy and attenuate hemorrhagic complications. METHODS: A series of pegylated and non-pegylated tPA-loaded liposomes were prepared and their surfaces were decorated with the peptide sequence (CQQHHLGGAKQAGDV) of fibrinogen gamma-chain that binds with GPIIb/IIIa expressed on activated platelets. All formulations were characterized for physical properties, stability and in vitro release profile...
June 2013: Pharmaceutical Research
Dror Ben-David, Samer Srouji, Keren Shapira-Schweitzer, Olga Kossover, Eran Ivanir, Gisela Kuhn, Ralph Müller, Dror Seliktar, Erella Livne
Bone repair strategies utilizing resorbable biomaterial implants aim to stimulate endogenous cells in order to gradually replace the implant with functional repair tissue. These biomaterials should therefore be biodegradable, osteoconductive, osteoinductive, and maintain their integrity until the newly formed host tissue can contribute proper function. In recent years there has been impressive clinical outcomes for this strategy when using osteoconductive hydrogel biomaterials in combination with osteoinductive growth factors such as human recombinant bone morphogenic protein (hrBMP-2)...
April 2013: Biomaterials
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