@article{781d9bd67434461f8e0025bfa1577cea,
title = "Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates",
abstract = "The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.",
author = "Vegas, {Arturo J.} and Omid Veiseh and Doloff, {Joshua C.} and Minglin Ma and Tam, {Hok Hei} and Kaitlin Bratlie and Jie Li and Bader, {Andrew R.} and Erin Langan and Karsten Olejnik and Patrick Fenton and Kang, {Jeon Woong} and Jennifer Hollister-Locke and Bochenek, {Matthew A.} and Alan Chiu and Sean Siebert and Katherine Tang and Siddharth Jhunjhunwala and Stephanie Aresta-Dasilva and Nimit Dholakia and Raj Thakrar and Thema Vietti and Michael Chen and Josh Cohen and Karolina Siniakowicz and Meirigeng Qi and James McGarrigle and Stephen Lyle and Harlan, {David M.} and Greiner, {Dale L.} and Jose Oberholzer and Weir, {Gordon C.} and Robert Langer and Anderson, {Daniel G.}",
note = "Funding Information: This work was supported jointly by the JDRF and Leona M. and the Harry B. Helmsley Charitable Trust (grant 3-SRA-2014-285-M-R), National Institutes of Health (NIH grants EB000244, EB000351, DE013023 and CA151884), NIH NIBIB (P41EB015871-27), MIT SkolTech initiative (J.W.K.), JDRF and the Department of Defense/Congressionally Directed Medical Research Programs (DOD/CDMRP postdoctoral fellowships 3-2013-178 and W81XWH-13-1-0215 for O.V.) and through a generous gift from the Tayebati Family Foundation. G.C.W. is supported by National Institutes of Health (NIH grants R01DK093909 and P30DK036836, the Joslin Diabetes Research Center and its Advanced Microscopy Core), as well as the Diabetes Research and Wellness Foundation. J.O. is supported by the National Institutes of Health (NIH/NIDDK) R01DK091526 and the Chicago Diabetes Project. This work was also supported in part by the Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute. We also thank the Koch Institute Swanson Biotechnology Center for technical support, specifically Tang Histology Facility, Microscopy, Flow Cytometry, Nanotechnology Materials, and Applied Therapeutics and Whole Animal Imaging. The authors would like to acknowledge the use of resources at W.M. Keck Biological Imaging Facility (Whitehead Institute). Publisher Copyright: {\textcopyright} 2016 Nature America, Inc. All rights reserved.",
year = "2016",
month = mar,
day = "1",
doi = "10.1038/nbt.3462",
language = "English (US)",
volume = "34",
pages = "345--352",
journal = "Nature biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "3",
}