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      Designing biomaterials with immunomodulatory properties for tissue engineering and regenerative medicine

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          Abstract

          Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune‐stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties—size, shape, chemical functionality—impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine. We begin by discussing what has been learned from studies conducted in the contexts of vaccines and immunotherapies. Next, research is highlighted that elucidates the properties of materials that polarize innate immune cells, including macrophages and dendritic cells, toward either inflammatory or wound healing phenotypes. We also discuss recent studies demonstrating that scaffolds used in tissue engineering applications can influence cells of the adaptive immune system—B and T cell lymphocytes—to promote regenerative tissue microenvironments. Through greater study of the intrinsic immunogenic features of implantable materials and scaffolds, new translational opportunities will arise to better control tissue engineering and regenerative medicine applications.

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          Most cited references147

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          Exploring the full spectrum of macrophage activation.

          Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
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            Macrophage plasticity and polarization: in vivo veritas.

            Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to IFNs, Toll-like receptor engagement, or IL-4/IL-13 signaling, macrophages undergo M1 (classical) or M2 (alternative) activation, which represent extremes of a continuum in a universe of activation states. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1-M2 or M2-like polarized activation. Functional skewing of mononuclear phagocytes occurs in vivo under physiological conditions (e.g., ontogenesis and pregnancy) and in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer). However, in selected preclinical and clinical conditions, coexistence of cells in different activation states and unique or mixed phenotypes have been observed, a reflection of dynamic changes and complex tissue-derived signals. The identification of mechanisms and molecules associated with macrophage plasticity and polarized activation provides a basis for macrophage-centered diagnostic and therapeutic strategies.
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              3D bioprinting of tissues and organs.

              Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

                Author and article information

                Contributors
                cmjewell@umd.edu
                Journal
                Bioeng Transl Med
                Bioeng Transl Med
                10.1002/(ISSN)2380-6761
                BTM2
                Bioengineering & Translational Medicine
                John Wiley and Sons Inc. (Hoboken )
                2380-6761
                16 May 2017
                June 2017
                : 2
                : 2 ( doiID: 10.1002/btm2.v2.2 )
                : 139-155
                Affiliations
                [ 1 ] Fischell Department of Bioengineering University of Maryland College Park MD 20742
                [ 2 ] Department of Microbiology and Immunology University of Maryland Medical School Baltimore MD 21201
                [ 3 ] Marlene and Stewart Greenebaum Cancer Center Baltimore MD 21201
                [ 4 ] United States Department of Veterans Affairs Baltimore MD 21201
                Author notes
                [*] [* ] Correspondence Christopher M. Jewell, Fischell Department of Bioengineering, 2212 Jeong H. Kim Engineering Building, College Park, MD 20742. Email: cmjewell@ 123456umd.edu .
                Article
                BTM210063
                10.1002/btm2.10063
                5579731
                28932817
                94d6ff48-96bd-42a0-a1c2-70c63aca1fb5
                © 2017 The Authors. Bioengineering & Translational Medicine is published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers

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

                History
                : 31 January 2017
                : 14 April 2017
                : 24 April 2017
                Page count
                Figures: 8, Tables: 0, Pages: 18, Words: 13463
                Funding
                Funded by: Alliance for Cancer Gene Therapy
                Award ID: 15051543
                Funded by: National Science Foundation
                Award ID: CAREER 1351688
                Funded by: American Association of Pharmaceutical Scientists
                Award ID: Pharmaceutics Doctoral Fellowship
                Funded by: National Multiple Sclerosis Society
                Award ID: RG‐1501‐02968
                Funded by: Melanoma Research Alliance
                Award ID: 348963
                Funded by: Damon Runyon Cancer Research Foundation
                Award ID: DRR3415
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                btm210063
                June 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.5 mode:remove_FC converted:16.11.2017

                biomaterial,immunology,intrinsic immunogenicity,nanoparticle and microparticle,regenerative medicine,tissue engineering,vaccine and immunotherapy

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