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Recently it has become appreciated that the ECM contains bioactive motifs that can directly modulate immune responses. This review describes strategies for engineering immunomodulatory biomaterials that utilize natural ECM\u2010derived molecules and have the potential to harness the immune system for applications ranging from tissue regeneration to drug delivery. A top\u2010down approach utilizes full\u2010length ECM proteins, including collagen, fibrin, or hyaluronic acid\u2010based materials, as well as matrices derived from decellularized tissue. These materials have the benefit of maintaining natural conformation and structure but are often heterogeneous and encumber precise control. By contrast, a bottom\u2010up approach leverages immunomodulatory domains, such as Arg\u2013Gly\u2013Asp (RGD), matrix metalloproteinase (MMP)\u2010sensitive peptides, or leukocyte\u2010associated immunoglobulin\u2010like receptor\u20101(LAIR\u20101) ligands, by incorporating them into synthetic materials. These materials have tunable control over immune cell functions and allow for combinatorial approaches. However, the synthetic approach lacks the full natural context of the original ECM protein. These two approaches provide a broad range of engineering techniques for immunomodulation through material interactions and hold the potential for the development of future therapeutic applications.<\/jats:p>","DOI":"10.1002\/adhm.201801578","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T03:30:51Z","timestamp":1549251051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":187,"title":["Extracellular Matrix\u2010Based Strategies for Immunomodulatory Biomaterials Engineering"],"prefix":"10.1002","volume":"8","author":[{"given":"Andrew T.","family":"Rowley","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of California  Irvine CA 92697 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raji R.","family":"Nagalla","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of California  Irvine CA 92697 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu\u2010Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of California  Irvine CA 92697 USA"},{"name":"Department of Biomedical Engineering University of California  Irvine CA 92697 USA"},{"name":"Department of Materials Science and Engineering University of California  Irvine CA 92697 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8904-7643","authenticated-orcid":false,"given":"Wendy F.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering University of California  Irvine CA 92697 USA"},{"name":"Department of Biomedical Engineering University of California  Irvine CA 92697 USA"},{"name":"The Edwards Lifesciences Center for Advanced Cardiovascular Technology University of California  Irvine CA 92697 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.2.149"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201402105"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2016.0538"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.12.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201800490"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2448"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1996.0186"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-013-9381-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2016.03.009"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-199209000-00033"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.22486"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphy.2017.00012"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2010.511353"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052554"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2009.03.005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(99)00052-9"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.35156"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.12423"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/09205063.2016.1155881"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2018.00116"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201700289"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.06.002"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.157"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/bm500735d"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.36343"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.02.074"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03522.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03523.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048266w"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1182\/blood.V89.1.166","volume":"89","author":"Kuijper P. 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