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Macrophage Immunomodulation Through New Polymers that Recapitulate Functional Effects of Itaconate as a Power House of Innate Immunity |
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| Authors: | Locke Davenport Huyer Serena Mandla Yufeng Wang Scott B Campbell Bess Yee Christian Euler Benjamin F Lai A Dawn Bannerman Dawn S Y Lin Miles Montgomery Kayla Nemr Timothy Bender Slava Epelman Radhakrishnan Mahadevan Milica Radisic |
| Institution: | 1. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5 Canada;2. Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9 Canada
Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4 Canada;3. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5 Canada Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4 Canada;4. Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9 Canada;5. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5 Canada Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9 Canada Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4 Canada;6. Toronto General Research Institute, University Health Network, Toronto, Ontario, M5G 2C4 Canada;7. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, M5S 3E5 Canada Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, M5S 3G9 Canada |
| Abstract: | Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation release from polyester backbones, ITA polymers result in the mechanism specific immunoregulatory properties on macrophage polarization in vitro. In a functional assay, the polymer-released ITA inhibits bacterial growth on acetate. Translation to an in vivo model of biomaterial associated inflammation, intraperitoneal injection of ITA polymers demonstrate a rapid resolution of inflammation in comparison to a control polymer silicone, demonstrating the value of sustained biomimetic presentation of ITA. |
| Keywords: | immunomodulation innate immunity itaconic acid macrophage polyester |