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      Cardiac Stem Cell-Loaded Delivery Systems: A New Challenge for Myocardial Tissue Regeneration

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          Abstract

          Cardiovascular disease (CVD) remains the leading cause of death in Western countries. Post-myocardial infarction heart failure can be considered a degenerative disease where myocyte loss outweighs any regenerative potential. In this scenario, regenerative biology and tissue engineering can provide effective solutions to repair the infarcted failing heart. The main strategies involve the use of stem and progenitor cells to regenerate/repair lost and dysfunctional tissue, administrated as a suspension or encapsulated in specific delivery systems. Several studies demonstrated that effectiveness of direct injection of cardiac stem cells (CSCs) is limited in humans by the hostile cardiac microenvironment and poor cell engraftment; therefore, the use of injectable hydrogel or pre-formed patches have been strongly advocated to obtain a better integration between delivered stem cells and host myocardial tissue. Several approaches were used to refine these types of constructs, trying to obtain an optimized functional scaffold. Despite the promising features of these stem cells’ delivery systems, few have reached the clinical practice. In this review, we summarize the advantages, and the novelty but also the current limitations of engineered patches and injectable hydrogels for tissue regenerative purposes, offering a perspective of how we believe tissue engineering should evolve to obtain the optimal delivery system applicable to the everyday clinical scenario.

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          Most cited references134

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          Designing hydrogels for controlled drug delivery

          Hydrogel delivery systems can leverage therapeutically beneficial outcomes of drug delivery and have found clinical use. Hydrogels can provide spatial and temporal control over the release of various therapeutic agents, including small-molecule drugs, macromolecular drugs and cells. Owing to their tunable physical properties, controllable degradability and capability to protect labile drugs from degradation, hydrogels serve as a platform in which various physiochemical interactions with the encapsulated drugs control their release. In this Review, we cover multiscale mechanisms underlying the design of hydrogel drug delivery systems, focusing on physical and chemical properties of the hydrogel network and the hydrogel-drug interactions across the network, mesh, and molecular (or atomistic) scales. We discuss how different mechanisms interact and can be integrated to exert fine control in time and space over the drug presentation. We also collect experimental release data from the literature, review clinical translation to date of these systems, and present quantitative comparisons between different systems to provide guidelines for the rational design of hydrogel delivery systems.
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            Hydrogels in pharmaceutical formulations.

            N. Peppas (2000)
            The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.
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              Hydrogels in regenerative medicine.

              Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 October 2020
                October 2020
                : 21
                : 20
                : 7701
                Affiliations
                [1 ]Department of Health Sciences, Magna Græcia University of Catanzaro, Loc. Germaneto, 88100 Catanzaro, Italy; antonia.mancuso@ 123456unicz.it (A.M.); fresta@ 123456unicz.it (M.F.)
                [2 ]Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Loc. Germaneto, 88100 Catanzaro, Italy; barone@ 123456unicz.it (A.B.); mchiara.cristiano@ 123456unicz.it (M.C.C.)
                [3 ]Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Loc. Germaneto, 88100 Catanzaro, Italy; cianflone@ 123456unicz.it
                Author notes
                [* ]Correspondence: paolino@ 123456unicz.it ; Tel.: +39-0961-369-4211
                Author information
                https://orcid.org/0000-0002-0915-8643
                https://orcid.org/0000-0001-8062-817X
                https://orcid.org/0000-0002-5223-9879
                Article
                ijms-21-07701
                10.3390/ijms21207701
                7589970
                33080988
                0380d8e6-7b99-435d-88f2-141a51a38a20
                © 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
                : 01 October 2020
                : 16 October 2020
                Categories
                Review

                Molecular biology
                patches,injectable hydrogel,myocardial regeneration,nanomedicine,cardiac stem cell,tissue engineering

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