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• W2320199442 abstract "Event Abstract Back to Event Nanoparticles composed of extracellular matrix for immune modulation Matthew Wolf1, 2, John Krill1, 2, Tony Wang1, Kaitlyn Sadtler1 and Jennifer H. Elisseeff1, 2 1 Johns Hopkins University School of Medicine, Translational Tissue Engineering Center, United States 2 Johns Hopkins University, Biomedical Engineering, United States Introduction: The extracellular matrix (ECM) is a critical component of the tissue microenvironment in homeostasis, wound healing, and disease. Scaffolds composed of decellularized tissues capture the complexity of the native ECM, and promote pro-regenerative effects via infiltrating immune cells. ECM scaffolds polarize macrophages along the M1 (pro-inflammatory) and M2 (anti-inflammatory) axis to influence the regenerative outcome. Nanoparticles, which have been used in drug delivery, have a wide biodistribution following injection. The goal of the present study was to prepare a nanoparticle formulation of ECM, and to characterize its immunomodulatory properties. Materials and Methods: Porcine bladder, small intestine, and cardiac tissues were decellularized by detergent and enzymatic treatment. Each ECM scaffold was homogenized to prepare ECM nanoparticles (ECM-NPs). Dynamic light scattering and transmission electron microscopy was used to determine the size distribution and zeta potential of ECM-NPs. Mouse bone marrow macrophages were isolated and exposed to ECM-NPs at multiple concentration, and their effect on macrophage activation was determined by immunofluorescence for NF-κB signaling and gene expression via qRT-PCR. ECM-NPs were compared to M1 (LPS+IFNγ) and M2 (IL-4) cytokine conditions. Further, cytokine secretion was evaluated via ELISA. Cardiac ECM-NPs were then fluorescently labeled and injected into the footpad, tail, or intraperitoneal space for live animal near-infrared imaging over a 5 day time course. Results and Discussion: Bladder, small intestine, and cardiac tissues were decellularized, removing the majority of cell components and nuclei creating a fibrous biologic ECM scaffold (Fig 1A). ECM scaffolds were successfully fragmented into ECM-NPs with monodisperse sizes ranging between 455-800 nm (Fig 1B), negative zeta potentials (-17.2 to -27.3 mV), and with no significant differences by tissue type. TEM revealed an irregular, globular morphology (Fig 1C). ECM-NPs polarized macrophages towards a mixed M1/M2 phenotype that was not dependent on ECM tissue source. ECM-NPs increased TNF-⍺, IL-1b, iNOS, and IL-10 expression in a dose dependent fashion (Fig 1D). TNF-⍺ and IL-10 production was verified at the protein level by ELISA, and confirmed dual pro-inflammatory and regulatory macrophage signaling. ECM-NPs rapidly activated NF- κB mediated pathways in macrophages with translocation of the p65 subunit (Fig 1D). Such activation is characteristic of pattern recognition receptor binding, suggesting direct innate immune system engagement. Cardiac ECM-NPs initiated immune activation in vivo following injection into the footpad, tail, or intraperiteal space wherein ECM-NPs trafficked to and accumulated in lymph nodes (Fig 1E). Free dye alone did not show accumulation indicating ECM-NP activation is necessary for the lymphatic response. Conclusions: ECM-NPs with sub-micron size distributions can be prepared from multiple tissue sources, and each tissue showed similar effects on macrophage gene expression and cytokine production in vitro. ECM-NPs induced a complex macrophage phenotype that had aspects of both M1 and M2 polarization, including TNF-⍺ production and IL-10 expression that exceeds cytokine stimulation alone. ECM-NPs are trafficked to lymph nodes in vivo and show promise as immune stimulating agents. Matthew Wolf was supported by the Hartwell Foundation Postdoctoral Fellowship Keywords: Extracellular Matrix, Drug delivery, nanoparticle, cell phenotype Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: New Frontier Oral Topic: Biomaterials in immune response Citation: Wolf M, Krill J, Wang T, Sadtler K and Elisseeff JH (2016). Nanoparticles composed of extracellular matrix for immune modulation. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02915 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Matthew Wolf John Krill Tony Wang Kaitlyn Sadtler Jennifer H Elisseeff Google Matthew Wolf John Krill Tony Wang Kaitlyn Sadtler Jennifer H Elisseeff Google Scholar Matthew Wolf John Krill Tony Wang Kaitlyn Sadtler Jennifer H Elisseeff PubMed Matthew Wolf John Krill Tony Wang Kaitlyn Sadtler Jennifer H Elisseeff Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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• W2320199442 title "Nanoparticles composed of extracellular matrix for immune modulation" @default.
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