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      Potential of Chitosan and Its Derivatives for Biomedical Applications in the Central Nervous System

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          Abstract

          It is well known that the central nervous system (CNS) has a limited regenerative capacity and that many therapeutic molecules cannot cross the blood brain barrier (BBB). The use of biomaterials has emerged as an alternative to overcome these limitations. For many years, biomedical applications of chitosan have been studied due to its remarkable biological properties, biocompatibility, and high versatility. Moreover, the interest in this biomaterial for CNS biomedical implementation has increased because of its ability to cross the BBB, mucoadhesiveness, and hydrogel formation capacity. Several chitosan-based biomaterials have been applied with promising results as drug, cell and gene delivery vehicles. Moreover, their capacity to form porous scaffolds and to bear cells and biomolecules has offered a way to achieve neural regeneration. Therefore, this review aims to bring together recent works that highlight the potential of chitosan and its derivatives as adequate biomaterials for applications directed toward the CNS. First, an overview of chitosan and its derivatives is provided with an emphasis on the properties that favor different applications. Second, a compilation of works that employ chitosan-based biomaterials for drug delivery, gene therapy, tissue engineering, and regenerative medicine in the CNS is presented. Finally, the most interesting trends and future perspectives of chitosan and its derivatives applications in the CNS are shown.

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          The contribution of astrocytes and microglia to traumatic brain injury.

          Traumatic brain injury (TBI) represents a major cause of death and disability in developed countries. Brain injuries are highly heterogeneous and can also trigger other neurological complications, including epilepsy, depression and dementia. The initial injury often leads to the development of secondary sequelae; cellular hyperexcitability, vasogenic and cytotoxic oedema, hypoxia-ischaemia, oxidative stress and inflammation, all of which influence expansion of the primary lesion. It is widely known that inflammatory events in the brain following TBI contribute to the widespread cell death and chronic tissue degeneration. Neuroinflammation is a multifaceted response involving a number of cell types, both within the CNS and in the peripheral circulation. Astrocytes and microglia, cells of the CNS, are considered key players in initiating an inflammatory response after injury. These cells are capable of secreting various cytokines, chemokines and growth factors, and following injury to the CNS, undergo changes in morphology. Ultimately, these changes can influence the local microenvironment and thus determine the extent of damage and subsequent repair. This review will focus on the roles of microglia and astrocytes following TBI, highlighting some of the key processes, pathways and mediators involved in this response. Additionally, both the beneficial and the detrimental aspects of these cellular responses will be examined using evidence from animal models and human post-mortem TBI studies.
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            Challenges and opportunities in exosome research—Perspectives from biology, engineering, and cancer therapy

            Exosomes are small (∼30–140 nm) lipid bilayer-enclosed particles of endosomal origin. They are a subset of extracellular vesicles (EVs) that are secreted by most cell types. There has been growing interest in exosome research in the last decade due to their emerging role as intercellular messengers and their potential in disease diagnosis. Indeed, exosomes contain proteins, lipids, and RNAs that are specific to their cell origin and could deliver cargo to both nearby and distant cells. As a result, investigation of exosome cargo contents could offer opportunities for disease detection and treatment. Moreover, exosomes have been explored as natural drug delivery vehicles since they can travel safely in extracellular fluids and deliver cargo to destined cells with high specificity and efficiency. Despite significant efforts made in this relatively new field of research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization, and lack of specific biomarkers. In this review, we summarize the current knowledge in exosome biogenesis, their roles in disease progression, and therapeutic applications and opportunities in bioengineering. Furthermore, we highlight the established and emerging technological developments in exosome isolation and characterization. We aim to consider critical challenges in exosome research and provide directions for future studies.
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              A Review on Chitin and Chitosan Polymers: Structure, Chemistry, Solubility, Derivatives, and Applications

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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                05 May 2020
                2020
                : 8
                : 389
                Affiliations
                [1] 1Biotecnología Industrial, CONACYT Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ) , Zapopan, Mexico
                [2] 2Unidad de Evaluación Preclínica, Biotecnología Médica y Farmacéutica, CONACYT Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ) , Guadalajara, Mexico
                [3] 3Servicio de Neurología, Instituto de Neurociencias, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos , Madrid, Spain
                Author notes

                Edited by: John Forsythe, Monash University, Australia

                Reviewed by: Giovanna Rassu, University of Sassari, Italy; Paolo Giunchedi, University of Sassari, Italy; Ryan James Gilbert, Rensselaer Polytechnic Institute, United States

                *Correspondence: Juan C. Mateos-Díaz, jcmateos@ 123456ciatej.mx

                This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2020.00389
                7214799
                32432095
                86891fe1-1536-44ac-8f7a-4ff7e6359d30
                Copyright © 2020 Ojeda-Hernández, Canales-Aguirre, Matias-Guiu, Gomez-Pinedo and Mateos-Díaz.

                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
                : 02 December 2019
                : 07 April 2020
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 177, Pages: 15, Words: 0
                Funding
                Funded by: Consejo Nacional de Ciencia y Tecnología 10.13039/501100003141
                Categories
                Bioengineering and Biotechnology
                Review

                chitosan,chitosan derivatives,central nervous system,drug delivery,tissue engineering,regenerative medicine

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