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      Engineering Immune Tolerance with Biomaterials

      1 , 1 , 2 , 3 , 4 , 5
      Advanced Healthcare Materials
      Wiley

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          Abstract

          Autoimmune diseases, rejection of transplanted organs and grafts, chronic inflammatory diseases, and immune-mediated rejection of biologic drugs impact a large number of people across the globe. New understanding of immune function is revealing exciting opportunities to help tackle these challenges by harnessing – or correcting - the specificity of immune function. However, realizing this potential requires precision control over the interaction between regulatory immune cues, antigens attacked during inflammation, and the tissues where these processes occur. Engineered materials – such as polymeric and lipid particles, scaffolds, and inorganic materials – offer powerful features that could help selectively regulate immune function during disease without compromising healthy immune functions. In this review, we highlight some of the exciting developments to leverage biomaterials as carriers, depots, scaffolds – and even as agents with intrinsic immunomodulatory features – to promote immunological tolerance. Autoimmune disease, inflammatory conditions, and rejection of organs and tissue grafts are all underpinned by undesirable immune reactions at cell, tissue, and systemic levels. Biomaterials offer powerful opportunities to control interactions across these scales to promote immunological tolerance that selectively controls inflammation. This review summarizes emerging opportunities in this area that exploit biomaterials as carriers, as as scaffolds, and as intrinsic modulatory materials.

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          Most cited references109

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          Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome.

          Many currently used and candidate vaccine adjuvants are particulate in nature, but their mechanism of action is not well understood. Here, we show that particulate adjuvants, including biodegradable poly(lactide-co-glycolide) (PLG) and polystyrene microparticles, dramatically enhance secretion of interleukin-1beta (IL-1beta) by dendritic cells (DCs). The ability of particulates to promote IL-1beta secretion and caspase 1 activation required particle uptake by DCs and NALP3. Uptake of microparticles induced lysosomal damage, whereas particle-mediated enhancement of IL-1beta secretion required phagosomal acidification and the lysosomal cysteine protease cathepsin B, suggesting a role for lysosomal damage in inflammasome activation. Although the presence of a Toll-like receptor (TLR) agonist was required to induce IL-1beta production in vitro, injection of the adjuvants in the absence of TLR agonists induced IL-1beta production at the injection site, indicating that endogenous factors can synergize with particulates to promote inflammasome activation. The enhancement of antigen-specific antibody production by PLG microparticles was independent of NALP3. However, the ability of PLG microparticles to promote antigen-specific IL-6 production by T cells and the recruitment and activation of a population of CD11b(+)Gr1(-) cells required NALP3. Our data demonstrate that uptake of microparticulate adjuvants by DCs activates the NALP3 inflammasome, and this contributes to their enhancing effects on innate and antigen-specific cellular immunity.
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            Therapeutic inflammatory monocyte modulation using immune-modifying microparticles.

            Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. However, no treatment option exists that is capable of modulating these cells specifically. We show that infused negatively charged, immune-modifying microparticles (IMPs), derived from polystyrene, microdiamonds, or biodegradable poly(lactic-co-glycolic) acid, were taken up by inflammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer trafficked to sites of inflammation; rather, IMP infusion caused their sequestration in the spleen through apoptotic cell clearance mechanisms and, ultimately, caspase-3-mediated apoptosis. Administration of IMPs in mouse models of myocardial infarction, experimental autoimmune encephalomyelitis, dextran sodium sulfate-induced colitis, thioglycollate-induced peritonitis, and lethal flavivirus encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Together, these data highlight the intricate interplay between scavenger receptors, the spleen, and inflammatory monocyte function and support the translation of IMPs for therapeutic use in diseases caused or potentiated by inflammatory monocytes.
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              Nanoparticle hydrophobicity dictates immune response.

              Understanding the interactions of nanomaterials with the immune system is essential for the engineering of new macromolecular systems for in vivo applications. Systematic study of immune activation is challenging due to the complex structure of most macromolecular probes. We present here the use of engineered gold nanoparticles to determine the sole effect of hydrophobicity on the immune response of splenocytes. The gene expression profile of a range of cytokines (immunological reporters) was analyzed against the calculated log P of the nanoparticle headgroups, with an essentially linear increase in immune activity with the increase in hydrophobicity observed in vitro. Consistent behavior was observed with in vivo mouse models, demonstrating the importance of hydrophobicity in immune system activation. © 2012 American Chemical Society
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                Author and article information

                Journal
                Advanced Healthcare Materials
                Adv. Healthcare Mater.
                Wiley
                21922640
                January 03 2019
                : 1801419
                Affiliations
                [1 ]Fischell Department of Bioengineering; University of Maryland; 8278 Paint Branch Drive RM 5110 College Park MD 20742 USA
                [2 ]Robert E. Fischell Institute for Biomedical Devices; 8278 Paint Branch Drive College Park MD 20742 USA
                [3 ]United States Department of Veterans Affairs; Baltimore VA Medical center; 10. N Green Street Baltimore MD 21201 USA
                [4 ]Department of Microbiology and Immunology; University of Maryland Medical School; 685 West Baltimore Street, HSF-I Suite 380 Baltimore MD 21201 USA
                [5 ]Marlene and Stewart Greenebaum Cancer Center; 22 South Greene Street Baltimore MD 21201 USA
                Article
                10.1002/adhm.201801419
                6384133
                30605264
                4e26b584-939b-4be4-bfea-847186dba57c
                © 2019

                http://doi.wiley.com/10.1002/tdm_license_1.1

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