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      Myocardial Matrix Hydrogels Mitigate Negative Remodeling and Improve Function in Right Heart Failure Model

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          Highlights

          • •

            LV- and RV-derived MM hydrogels improve RV contractility over time, preserve RV volumes, and reduce RV-free wall thickness.

          • •

            LV-derived MM hydrogels improve RVEF.

          • •

            LV- and RV-derived MM hydrogels reduce hypertrophy and interstitial fibrosis, decrease myofibroblast density, and enhance neovascularization.

          • •

            Although both MM hydrogels enhance gene expression related to neovascularization, contractility, and cardiac development, the RV-derived MM hydrogel enhances inflammatory and fibrotic gene expression, suggesting greater therapeutic benefit of the LV-derived MM hydrogel.

          Summary

          This study evaluates the effectiveness of myocardial matrix (MM) hydrogels in mitigating negative right ventricular (RV) remodeling in a rat model of RV heart failure. The goal was to assess whether a hydrogel derived from either the right or left ventricle could promote cardiac repair. Injured rat right ventricles were injected with either RV-or left ventricular–derived MM hydrogels. Both hydrogels improved RV function and morphology and reduced negative remodeling. This study supports the potential of injectable biomaterial therapies for treating RV heart failure.

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          Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells.

          Kaitlyn Sadtler, Kenneth Estrellas, Brian Allen … (2016)
          Immune-mediated tissue regeneration driven by a biomaterial scaffold is emerging as an innovative regenerative strategy to repair damaged tissues. We investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration. The scaffolds induced a pro-regenerative response, characterized by an mTOR/Rictor-dependent T helper 2 pathway that guides interleukin-4-dependent macrophage polarization, which is critical for functional muscle recovery. Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair.
          Article 0 comments Cited 218 times – based on 0 reviews     Review now
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            Extracellular matrix hydrogels from decellularized tissues: Structure and function

            Lindsey Saldin, Madeline Cramer, Sachin S Velankar … (2017)
            Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed.
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              Macrophage phenotype as a determinant of biologic scaffold remodeling.

              Norma J. Stewart, Stephen Badylak, G McCabe … (2008)
              Macrophage phenotype can be characterized as proinflammatory (M1) or immunomodulatory and tissue remodeling (M2). The present study used a rat model to determine the macrophage phenotype at the site of implantation of two biologic scaffolds that were derived from porcine small intestinal submucosa (SIS) and that differed mainly according to their method of processing: the Restore device (SIS) and the CuffPatch device (carbodiimide crosslinked form of porcine-derived SIS (CDI-SIS)). An autologous tissue graft was used as a control implant. Immunohistologic methods were used to identify macrophage surface markers CD68 (pan macrophages), CD80 and CCR7 (M1 profile), and CD163 (M2 profile) during the remodeling process. All graft sites were characterized by the dense population of CD68+ mononuclear cells present during the first 4 weeks. The SIS device elicited a predominantly CD163+ response (M2 profile, p < 0.001) and showed constructive remodeling at 16 weeks. The CDI-SIS device showed a predominately CD80+ and CCR7+ response (M1 profile, p < 0.03), and at 16 weeks was characterized by chronic inflammation. The autologous tissue graft showed a predominately CD163+ response (M2) at 1 week, with a dual M1/M2 population (CD80+, CCR7+, and CD163+) by 2 and 4 weeks and moderately well organized connective tissue by 16 weeks. The processing methods used during the manufacturing of a biologic scaffold can have a profound influence upon the macrophage phenotype profile and downstream remodeling events. Routine histologic examination alone is inadequate to determine the phenotype of mononuclear cells that participate in the host response to the scaffold.
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                Author and article information

                Contributors
                Karen L. Christman: @ChristmanLab
                Journal
                Journal ID (nlm-ta): JACC Basic Transl Sci
                Journal ID (iso-abbrev): JACC Basic Transl Sci
                Title: JACC: Basic to Translational Science
                Publisher: Elsevier
                ISSN (Electronic): 2452-302X
                Publication date PMC-release: 06 March 2024
                Publication date Collection: March 2024
                Publication date (Electronic): 06 March 2024
                Volume: 9
                Issue: 3
                Pages: 322-338
                Affiliations
                [a ]Shu Chien-Gene Lay Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California-San Diego, San Diego, California, USA
                [b ]Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA
                Author notes
                [∗ ] Address for correspondence: Dr Karen L. Christman, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA. kchristman@ 123456ucsd.edu @ChristmanLab
                Article
                Publisher Item ID: S2452-302X(24)00010-X
                DOI: 10.1016/j.jacbts.2024.01.006
                PMC ID: 10978413
                PubMed ID: 38559631
                SO-VID: 51e32ac1-8c07-467d-a9d8-d4e32b046498
                Copyright © © 2024 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 25 October 2023
                Date revision received : 4 January 2024
                Date accepted : 8 January 2024
                Categories
                Subject: Original Research - Preclinical

                Keywords: biomaterial,extracellular matrix,hydrogel,negative right ventricular remodeling,right ventricle
                Data availability:
                Keywords: biomaterial, extracellular matrix, hydrogel, negative right ventricular remodeling, right ventricle

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