NVR (Neuronal and Vascular Reconstruction) Research Ltd
Specialties: Chemist and Biologist, specialties in synthesis and characterization of nanoparticles for medical applications, development of tissue engineered implants for the CNS and PNS, and immunology
Primary Affiliation: NVR (Neuronal and Vascular Reconstruction) Research Ltd - Israel
PubMed Central Citations
47PubMed Central Citations
Biomed Mater 2015 Oct 20;10(5):051001. Epub 2015 Oct 20.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4701-057 Braga, Portugal. ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal. R C Assunção-Silva and C C Oliveira contributed equally to this work.
Neural Regen Res 2015 Feb;10(2):189-91
N.V.R Research Ltd., 11 Heharash St, Ness-Ziona 74031, Israel.
BioMed Research International, vol. 2014, Article ID 267808, 10 pages, 2014. doi:10.1155/2014/267808
BioMed Research International
Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF), glial cell-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (FGF-2). Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37 °C. The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG) cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF a desirable scaffold for the reconstruction of severed peripheral nerve.
New functional crosslinked poly(ethylene glycol) (PEG) micrometer-sized particles of narrow size distribution were prepared by dispersion co-polymerization in an aqueous continuous phase of the monomers methacrylate polyethylene glycol carboxylic acid (MA-PEG-COOH) or methacrylate polyethylene glycol amine (MA-PEG-NH2) with polyethylene glycol methacrylate ether (MA-PEG-OCH3) and the crosslinker monomer polyethylene glycol dimethacrylate (PEDMA). The effect of various polymerization parameters, e.g., total monomer concentration, crosslinker monomer concentration, initiator concentration and stabilizer concentration and Mw on the size, size distribution and polymerization yield of the produced particles has been studied. As a model for enzyme immobilization, trypsin was covalently bound to the functional PEG particles. A substantial loss in the activity and an increase in the stability of the conjugated enzyme, as compared to the free one, were demonstrated.
Journal of Photochemistry and Photobiology A: Chemistry. 2012;228(1):1-68
Journal of Photochemistry and Photobiology A: Chemistry
Fluorescent nanoparticles continue to be of wide interest, as they have many advantages over single fluorescent molecules for biological imaging and sensing applications, such as increased fluorescence intensity and reduced photobleaching. In the following work, styrene was copolymerised with a newly synthesised, fluorescein-based, vinylic crosslinking monomer, by emulsion polymerisation, to create a series of different sized fluorescent nanoparticles (35–100 nm), each of narrow size-distribution. The particles were found to be highly fluorescent and with lower photobleaching compared to fluorescein isothiocyanate (FITC), offering an attractive alternative. The fluorescence excitation and emission spectra were recorded, being similar to fluorescein, but with interesting variation in the excitation spectra. The particles also have a wide range of potential uses, such as examining particle uptake activity of a macrophage cell line, also demonstrated. The nanoparticles were coated with albumin to provide functionality for potential conjugation to biological targeting agents
Advanced Engineering Materials, in Advanced Biomaterials, 2009, 11(12): B251-B260
Advanced Engineering Materials, in Advanced Biomaterials
Thrombin is the final protease produced in the clotting pathways. Thrombin has been used in the clinic more than six decades for topical hemostasis and wound management. In human plasma the half-life of thrombin is shorter than 15 seconds due to close control by inhibitors. In order to stabilize thrombin, this enzyme was conjugated covalently and physically to g-Fe2O3 magnetic nanoparticles. The physical conjugation was accomplished through adsorption of thrombin to BSA coating on the nanoparticles. The coagulant activity of the covalently bound thrombin was significantly lower than that of the physically adsorbed thrombin. Leakage of the physically bound thrombin into PBS containing 4% HSA was negligible. The physical conjugation of thrombin onto the nanoparticles stabilized the thrombin against its major inhibitor antithrombin III and improved its storage stability. At optimal CaCl2 concentration, the clotting time by the bound thrombin is shorter than that of the free enzyme. This novel conjugated thrombin may be an efficient candidate for topical hemostasis and wound healing.
Biomaterials 31 (2010) 741–747
Thrombin has been clinically used for topical hemostasis and wound management for more than six decades. The half-life of thrombin in human plasma is shorter than 15 s due to close control by inhibitors. In order to stabilize the thrombin, it was bound to maghemite (gama-Fe2O3) nanoparticles, as demonstrated in previous work. The aim of the present study was to examine the efficiency of the bound thrombin for wound healing applications compared to the free thrombin. For this purpose incisional wounds on rat skin were treated with a mixture of fibrinogen, CaCl2 solution and free or bound thrombin. The wounds’ edges were then approximated by skin staples. The control incisional wounds were closed with staples only. In the course of 28 days of healing the highest values of skin tensile strength were observed following treatment with the bound thrombin. Significantly lower values of tensile strength were observed following treatment with the free thrombin, and the lowest values were obtained following treatment with staples only. The histological findings correlate with the mechanical strength measurements, which demonstrate the most advanced stages of healing following treatment with the bound thrombin.
J Biomed Mater Res A. 2008 Jun 15;85(4):1011-21
Journal of Biomedical Materials Research Part A
Uniform magnetic nanoparticles (MNP) were prepared by nucleation followed by controlled growth of maghemite thin films onto porcine gelatin nuclei. The formed gelatin containing MNP (Gel-MNP) were then coated with dextran (Gel-MNP-Dex) followed by human serum albumin (Gel-MNP-Dex-HSA). Since these MNP are designated for clinical applications, studies concerning the immunogenicity of their antigenic components (porcine gelatin, dextran, and HSA) have been performed in BALB-C mice. These studies demonstrated that plasma of nonimmunized mice already contains basal levels of natural antibodies against all of these antigenic components. This work also demonstrated that the conjugated gelatin is a weak immunogen: Intraperitoneal injection of the various MNP (Gel-MNP, Gel-MNP-Dex dispersed in PBS emulsified with Incomplete Freund’s Adjuvant (IFA) mineral oil and Gel-MNP-Dex-HSA dispersed in PBS) did not increase significantly the acquired anti-gelatin antibody titers. Exceptional behavior was observed following immunization with Gel-MNP-Dex-HSA dispersed in PBS emulsified with IFA, which exhibited an adjuvant effect and turned gelatin into a stronger immunogen. In contrast to gelatin, the conjugated HSA and dextran were found to be strong immunogens. The possibility that the various MNP will not induce an autoimmune response as a result of their clinical use is discussed in the contest of the protective role of the natural antibodies.