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      Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke

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          Abstract

          Inflammation is a major pathological event following ischemic stroke that contributes to secondary brain tissue damage leading to poor functional recovery. Following the initial ischemic insult, post-stroke inflammatory damage is driven by initiation of a central and peripheral innate immune response and disruption of the blood-brain barrier (BBB), both of which are triggered by the release of pro-inflammatory cytokines and infiltration of circulating immune cells. Stroke therapies are limited to early cerebral blood flow reperfusion, and whilst current strategies aim at targeting neurodegeneration and/or neuroinflammation, innovative research in the field of regenerative medicine aims at developing effective treatments that target both the acute and chronic phase of inflammation. Anti-inflammatory regenerative strategies include the use of nanoparticles and hydrogels, proposed as therapeutic agents and as a delivery vehicle for encapsulated therapeutic biological factors, anti-inflammatory drugs, stem cells, and gene therapies. Biomaterial strategies—through nanoparticles and hydrogels—enable the administration of treatments that can more effectively cross the BBB when injected systemically, can be injected directly into the brain, and can be 3D-bioprinted to create bespoke implants within the site of ischemic injury. In this review, these emerging regenerative and anti-inflammatory approaches will be discussed in relation to ischemic stroke, with a perspective on the future of stroke therapies.

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          Most cited references151

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          Three-dimensional flexible and conductive interconnected graphene networks grown by chemical vapour deposition.

          Integration of individual two-dimensional graphene sheets into macroscopic structures is essential for the application of graphene. A series of graphene-based composites and macroscopic structures have been recently fabricated using chemically derived graphene sheets. However, these composites and structures suffer from poor electrical conductivity because of the low quality and/or high inter-sheet junction contact resistance of the chemically derived graphene sheets. Here we report the direct synthesis of three-dimensional foam-like graphene macrostructures, which we call graphene foams (GFs), by template-directed chemical vapour deposition. A GF consists of an interconnected flexible network of graphene as the fast transport channel of charge carriers for high electrical conductivity. Even with a GF loading as low as ∼0.5 wt%, GF/poly(dimethyl siloxane) composites show a very high electrical conductivity of ∼10 S cm(-1), which is ∼6 orders of magnitude higher than chemically derived graphene-based composites. Using this unique network structure and the outstanding electrical and mechanical properties of GFs, as an example, we demonstrate the great potential of GF/poly(dimethyl siloxane) composites for flexible, foldable and stretchable conductors. © 2011 Macmillan Publishers Limited. All rights reserved
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            Microglia and macrophages in brain homeostasis and disease

            Microglia and non-parenchymal macrophages in the brain are mononuclear phagocytes that are increasingly recognized to be essential players in the development, homeostasis and diseases of the central nervous system. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made towards our understanding of the embryonic origins, developmental programmes and functions of these cells. These exciting discoveries, some of which are still controversial, also raise many new questions, which makes brain macrophage biology a fast-growing field at the intersection of neuroscience and immunology. Here, we review the current knowledge of how and where brain macrophages are generated, with a focus on parenchymal microglia. We also discuss their normal functions during development and homeostasis, the disturbance of which may lead to various neurodegenerative and neuropsychiatric diseases.
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              Biomedical applications of graphene and graphene oxide.

              Graphene has unique mechanical, electronic, and optical properties, which researchers have used to develop novel electronic materials including transparent conductors and ultrafast transistors. Recently, the understanding of various chemical properties of graphene has facilitated its application in high-performance devices that generate and store energy. Graphene is now expanding its territory beyond electronic and chemical applications toward biomedical areas such as precise biosensing through graphene-quenched fluorescence, graphene-enhanced cell differentiation and growth, and graphene-assisted laser desorption/ionization for mass spectrometry. In this Account, we review recent efforts to apply graphene and graphene oxides (GO) to biomedical research and a few different approaches to prepare graphene materials designed for biomedical applications. Because of its excellent aqueous processability, amphiphilicity, surface functionalizability, surface enhanced Raman scattering (SERS), and fluorescence quenching ability, GO chemically exfoliated from oxidized graphite is considered a promising material for biological applications. In addition, the hydrophobicity and flexibility of large-area graphene synthesized by chemical vapor deposition (CVD) allow this material to play an important role in cell growth and differentiation. The lack of acceptable classification standards of graphene derivatives based on chemical and physical properties has hindered the biological application of graphene derivatives. The development of an efficient graphene-based biosensor requires stable biofunctionalization of graphene derivatives under physiological conditions with minimal loss of their unique properties. For the development graphene-based therapeutics, researchers will need to build on the standardization of graphene derivatives and study the biofunctionalization of graphene to clearly understand how cells respond to exposure to graphene derivatives. Although several challenging issues remain, initial promising results in these areas point toward significant potential for graphene derivatives in biomedical research.
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                Author and article information

                Contributors
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                03 September 2018
                2018
                : 9
                : 734
                Affiliations
                Faculty of Biology, Medicine and Health, The University of Manchester , Manchester, United Kingdom
                Author notes

                Edited by: Rick Dijkhuizen, University Medical Center Utrecht, Netherlands

                Reviewed by: Maxime Gauberti, INSERM U1237 Physiopathologie et Imagerie des Troubles Neurologiques (PhIND), France; Adam Denes, Institute of Experimental Medicine (MTA), Hungary

                *Correspondence: Emmanuel Pinteaux emmanuel.pinteaux@ 123456manchester.ac.uk

                This article was submitted to Stroke, a section of the journal Frontiers in Neurology

                †Joint first authors

                Article
                10.3389/fneur.2018.00734
                6129611
                30233484
                38879ca2-527f-407f-a2e1-7de23fc93986
                Copyright © 2018 Rajkovic, Potjewyd and Pinteaux.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 June 2018
                : 13 August 2018
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 179, Pages: 15, Words: 12964
                Funding
                Funded by: Medical Research Council 10.13039/501100000265
                Funded by: Engineering and Physical Sciences Research Council 10.13039/501100000266
                Categories
                Neurology
                Review

                Neurology
                stroke,neuroinflammation,stem cells,hydrogels,nanoparticles
                Neurology
                stroke, neuroinflammation, stem cells, hydrogels, nanoparticles

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