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      Inflammation in Cardiovascular Tissue Engineering: The Challenge to a Promise: A Minireview

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          Abstract

          Tissue engineering employs scaffolds, cells, and stimuli brought together in such a way as to mimic the functional architecture of the target tissue or organ. Exhilarating advances in tissue engineering and regenerative medicine allow us to envision in vitro creation or in vivo regeneration of cardiovascular tissues. Such accomplishments have the potential to revolutionize medicine and greatly improve our standard of life. However, enthusiasm has been hampered in recent years because of abnormal reactions at the implant-host interface, including cell proliferation, fibrosis, calcification and degeneration, as compared to the highly desired healing and remodeling. Animal and clinical studies have highlighted uncontrolled chronic inflammation as the main cause of these processes. In this minireview, we present three case studies highlighting the importance of inflammation in tissue engineering heart valves, vascular grafts, and myocardium and propose to focus on the endothelial barrier, the “final frontier” endowed with the natural potential and ability to regulate inflammatory signals.

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          Most cited references134

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          Inflammation in atherosclerosis: from pathophysiology to practice.

          Until recently, most envisaged atherosclerosis as a bland arterial collection of cholesterol, complicated by smooth muscle cell accumulation. According to that concept, endothelial denuding injury led to platelet aggregation and release of platelet factors which would trigger the proliferation of smooth muscle cells in the arterial intima. These cells would then elaborate an extracellular matrix that would entrap lipoproteins, forming the nidus of the atherosclerotic plaque. Beyond the vascular smooth muscle cells long recognized in atherosclerotic lesions, subsequent investigations identified immune cells and mediators at work in atheromata, implicating inflammation in this disease. Multiple independent pathways of evidence now pinpoint inflammation as a key regulatory process that links multiple risk factors for atherosclerosis and its complications with altered arterial biology. Knowledge has burgeoned regarding the operation of both innate and adaptive arms of immunity in atherogenesis, their interplay, and the balance of stimulatory and inhibitory pathways that regulate their participation in atheroma formation and complication. This revolution in our thinking about the pathophysiology of atherosclerosis has now begun to provide clinical insight and practical tools that may aid patient management. This review provides an update of the role of inflammation in atherogenesis and highlights how translation of these advances in basic science promises to change clinical practice.
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            On the mechanisms of biocompatibility.

            The manner in which a mutually acceptable co-existence of biomaterials and tissues is developed and sustained has been the focus of attention in biomaterials science for many years, and forms the foundation of the subject of biocompatibility. There are many ways in which materials and tissues can be brought into contact such that this co-existence may be compromised, and the search for biomaterials that are able to provide for the best performance in devices has been based upon the understanding of all the interactions within biocompatibility phenomena. Our understanding of the mechanisms of biocompatibility has been restricted whilst the focus of attention has been long-term implantable devices. In this paper, over 50 years of experience with such devices is analysed and it is shown that, in the vast majority of circumstances, the sole requirement for biocompatibility in a medical device intended for long-term contact with the tissues of the human body is that the material shall do no harm to those tissues, achieved through chemical and biological inertness. Rarely has an attempt to introduce biological activity into a biomaterial been clinically successful in these applications. This essay then turns its attention to the use of biomaterials in tissue engineering, sophisticated cell, drug and gene delivery systems and applications in biotechnology, and shows that here the need for specific and direct interactions between biomaterials and tissue components has become necessary, and with this a new paradigm for biocompatibility has emerged. It is believed that once the need for this change is recognised, so our understanding of the mechanisms of biocompatibility will markedly improve.
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              Interactions between extracellular matrix and growth factors in wound healing.

              Dynamic interactions between growth factors and extracellular matrix (ECM) are integral to wound healing. These interactions take several forms that may be categorized as direct or indirect. The ECM can directly bind to and release certain growth factors (e.g., heparan sulfate binding to fibroblast growth factor-2), which may serve to sequester and protect growth factors from degradation, and/or enhance their activity. Indirect interactions include binding of cells to ECM via integrins, which enables cells to respond to growth factors (e.g., integrin binding is necessary for vascular endothelial growth factor-induced angiogenesis) and can induce growth factor expression (adherence of monocytes to ECM stimulates synthesis of platelet-derived growth factor). Additionally, matrikines, or subcomponents of ECM molecules, can bind to cell surface receptors in the cytokine, chemokine, or growth factor families and stimulate cellular activities (e.g., tenascin-C and laminin bind to epidermal growth factor receptors, which enhances fibroblast migration). Growth factors such as transforming growth factor-beta also regulate the ECM by increasing the production of ECM components or enhancing synthesis of matrix degrading enzymes. Thus, the interactions between growth factors and ECM are bidirectional. This review explores these interactions, discusses how they are altered in difficult to heal or chronic wounds, and briefly considers treatment implications.
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                Author and article information

                Journal
                Int J Inflam
                IJI
                International Journal of Inflammation
                SAGE-Hindawi Access to Research
                2042-0099
                2011
                9 July 2011
                : 2011
                : 958247
                Affiliations
                Biocompatibility and Tissue Regeneration Laboratory, Department of Bioengineering, Clemson University, 304 Rhodes Center, Clemson, SC 29634, USA
                Author notes
                *Dan T. Simionescu: dsimion@ 123456clemson.edu

                Academic Editor: Adrian Chester

                Article
                10.4061/2011/958247
                3132660
                21755031
                2765fe75-849a-4a50-9f70-4313086369ba
                Copyright © 2011 Agneta Simionescu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 March 2011
                : 10 May 2011
                Categories
                Review Article

                Immunology
                Immunology

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