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      Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction

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          Abstract

          Despite the success of current therapies for acute myocardial infarction (MI), many patients still develop adverse cardiac remodeling and heart failure. With the growing prevalence of heart failure, a new therapy is needed that can prevent remodeling and support tissue repair. Herein, we report on injectable recombinant human collagen type I (rHCI) and type III (rHCIII) matrices for treating MI. Injecting rHCI or rHCIII matrices in mice during the late proliferative phase post-MI restores the myocardium’s mechanical properties and reduces scar size, but only the rHCI matrix maintains remote wall thickness and prevents heart enlargement. rHCI treatment increases cardiomyocyte and capillary numbers in the border zone and the presence of pro-wound healing macrophages in the ischemic area, while reducing the overall recruitment of bone marrow monocytes. Our findings show functional recovery post-MI using rHCI by promoting a healing environment, cardiomyocyte survival, and less pathological remodeling of the myocardium.

          Abstract

          Many patients, following therapy for acute myocardial infarction, develop adverse cardiac remodelling. Here the authors present injectable recombinant human collagen 10 of 10 type I and III matrices that are able to limit adverse remodelling and improve function of the myocardium.

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          Review collagen-based biomaterials for wound healing.

          With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, nontoxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular interactions of collagen in vivo; the recent use of natural collagen in sponges, injectables, films and membranes, dressings, and skin grafts; and the on-going development of synthetic collagen mimetic peptides as pylons to anchor cytoactive agents in wound beds.
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            The extracellular matrix in myocardial injury, repair, and remodeling.

            The cardiac extracellular matrix (ECM) not only provides mechanical support, but also transduces essential molecular signals in health and disease. Following myocardial infarction, dynamic ECM changes drive inflammation and repair. Early generation of bioactive matrix fragments activates proinflammatory signaling. The formation of a highly plastic provisional matrix facilitates leukocyte infiltration and activates infarct myofibroblasts. Deposition of matricellular proteins modulates growth factor signaling and contributes to the spatial and temporal regulation of the reparative response. Mechanical stress due to pressure and volume overload and metabolic dysfunction also induce profound changes in ECM composition that contribute to the pathogenesis of heart failure. This manuscript reviews the role of the ECM in cardiac repair and remodeling and discusses matrix-based therapies that may attenuate remodeling while promoting repair and regeneration.
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              Bone Marrow-Derived Macrophages (BMM): Isolation and Applications

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                Author and article information

                Contributors
                esuuronen@ottawaheart.ca
                ealarcon@ottawaheart.ca
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                25 October 2019
                25 October 2019
                2019
                : 10
                : 4866
                Affiliations
                [1 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, BioEngineering and Therapeutic Solutions (BEaTS), Division of Cardiac Surgery, , University of Ottawa Heart Institute, ; 40 Ruskin street, Ottawa, ON K1Y4W7 Canada
                [2 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Department of Cellular & Molecular Medicine, , University of Ottawa, ; 451 Smyth Road, Ottawa, ON K1H8M5 Canada
                [3 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Department of Radiology, Faculty of Medicine, , University of Ottawa, ; 501 Smyth Road, Ottawa, ON K1H8L6 Canada
                [4 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Cardiac Function Laboratory, , University of Ottawa Heart Institute, ; 40 Ruskin street, Ottawa, ON K1Y4W7 Canada
                [5 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Cardiac Electrophysiology Lab, , University of Ottawa Heart Institute, ; 40 Ruskin street, Ottawa, ON K1Y4W7 Canada
                [6 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Cardiometabolic microRNA Laboratory, , University of Ottawa Heart Institute, ; 40 Ruskin street, Ottawa, ON K1Y4W7 Canada
                [7 ]ISNI 0000 0001 2182 2255, GRID grid.28046.38, Department of Biochemistry, Microbiology, and Immunology, , University of Ottawa, ; 451 Smyth Road, Ottawa, ON K1H8M5 Canada
                Author information
                http://orcid.org/0000-0003-2291-4164
                http://orcid.org/0000-0001-8084-9298
                http://orcid.org/0000-0001-5100-6179
                Article
                12748
                10.1038/s41467-019-12748-8
                6814728
                31653830
                aac789dd-2931-4f23-94dd-10871b5ff373
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 September 2018
                : 26 September 2019
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                cardiac device therapy,translational research
                Uncategorized
                cardiac device therapy, translational research

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