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      Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

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          Abstract

          Hydrogel-based nonviral gene delivery constitutes a powerful strategy in various regenerative medicine scenarios, as those concerning the treatment of musculoskeletal, cardiovascular, or neural tissues disorders as well as wound healing. By a minimally invasive administration, these systems can provide a spatially and temporarily defined supply of specific gene sequences into the target tissue cells that are overexpressing or silencing the original gene, which can promote natural repairing mechanisms to achieve the desired effect. In the present work, we provide an overview of the most avant-garde approaches using various hydrogels systems for controlled delivery of therapeutic nucleic acid molecules in different regenerative medicine approaches.

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          Most cited references115

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          The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

          Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds.
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            Gene therapy clinical trials worldwide to 2017: An update

            To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and the genes that have been transferred. Details of the analyses presented, and our searchable database are available via The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in gene therapy clinical trials around the world, and discuss key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies, which have the potential to transform the field moving forward.
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              The chemistry and engineering of polymeric hydrogel adhesives for wound closure: a tutorial.

              The closure and repair of wounds after traumatic or surgical injury is of significant clinical and research importance. While sutures remain the common wound closure technique, they have many disadvantages. Consequently, polymeric hydrogel adhesives have emerged as essential materials for wound management and repair because of their tunable chemical and physical properties, which enable them to adhere or stick to tissues, possess sufficient mechanical strength to stay intact and be subsequently removed, provide complete wound occlusion, and act as a barrier to bacterial infection. Moreover, these materials absorb wound exudates and keep the wound moist for faster healing. This tutorial review summarizes the key chemical features that enabled the development and use of polymeric hydrogels as wound adhesives, sealants, and hemostats, their design requirements, synthetic routes, determination of properties, and the tests needed to evaluate their performances. This tutorial review is a reference and a starting point for scientists and clinicians working or interested in the field of wound management and, importantly, for the general audience who is interested in polymers for medical applications.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                10 August 2020
                August 2020
                : 12
                : 8
                : 752
                Affiliations
                [1 ]Cell Therapy and Regenerative Medicine Unit, Centro de Investigacións Científicas Avanzadas (CICA), Universidade da Coruña, 15071 A Coruña, Spain; natalia.carballo@ 123456udc.es (N.C.-P.); i.fuentes@ 123456udc.es (I.F.-B.); s.diaz1@ 123456udc.es (S.D.-P.)
                [2 ]Departamento de Fisioterapia, Medicina y Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidade da Coruña (UDC), Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), 15071 A Coruña, Galicia, Spain
                Author notes
                [* ]Correspondence: ana.rey.rico@ 123456udc.es ; Tel.: +34-881-015-543
                Author information
                https://orcid.org/0000-0001-7161-5027
                https://orcid.org/0000-0001-9776-2180
                https://orcid.org/0000-0003-1682-498X
                Article
                pharmaceutics-12-00752
                10.3390/pharmaceutics12080752
                7464633
                32785171
                843bd9f2-3967-46e9-ad51-46ad8b980ab5
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 June 2020
                : 07 August 2020
                Categories
                Review

                musculoskeletal tissue,cardiovascular tissue,wound healing,nervous tissue,gene therapy,controlled delivery,hydrogels,nonviral vectors

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