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The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross\u2010linking, which increases ECM mechanical stiffness compared to native arteries. Herein, the importance of maintaining ECM mechanocompatibility is demonstrated, and a mechanocompatible strategy to immobilize heparin onto the ECM via a biodegradable elastomer is described. Specifically, poly(1,8\u2010octamethylene citrate)\u2010<jats:italic>co<\/jats:italic>\u2010cysteine is hybridized to the ECM, forming a polymer\u2010ECM composite that allows for heparin immobilization via maleimide\u2013thiol \u201cclick\u201d chemistry. Heparinized composites reduce platelet adhesion by &gt;60% in vitro, without altering the elastic modulus of the ECM. In a rat abdominal aortic interposition model, intimal hyperplasia in heparinized mechanocompatible grafts is 65% lower when compared to ECM\u2010only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2\u2010fold) and increased macrophage infiltration (3.5\u2010fold) compared to ECM\u2010only control grafts. All grafts show similar, partial endothelial cell coverage and little to no ECM remodeling. Overall, a mechanocompatible strategy to improve ECM thromboresistance is described and the importance of ECM mechanical properties for proper in vivo graft performance is highlighted.<\/jats:p>","DOI":"10.1002\/adhm.201501003","type":"journal-article","created":{"date-parts":[[2016,4,25]],"date-time":"2016-04-25T00:45:33Z","timestamp":1461545133000},"page":"1594-1605","source":"Crossref","is-referenced-by-count":23,"title":["Mechanocompatible Polymer\u2010Extracellular\u2010Matrix Composites for Vascular Tissue Engineering"],"prefix":"10.1002","volume":"5","author":[{"given":"Bin","family":"Jiang","sequence":"first","affiliation":[{"name":"Biomedical Engineering Department Northwestern University  Evanston IL 60208 USA"},{"name":"Comprehensive Transplant Center Feinberg School of Medicine Northwestern University  Chicago IL 60611 USA"},{"name":"Department of Surgery Northwestern University Feinberg School of Medicine  Chicago IL 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Suen","sequence":"additional","affiliation":[{"name":"Weinberg College of Arts and Sciences Northwestern University  Evanston IL 60208 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao\u2010Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Feinberg School of Medicine Northwestern University  Chicago IL 60611 USA"},{"name":"Department of Surgery Northwestern University Feinberg School of Medicine  Chicago IL 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng J.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Comprehensive Transplant Center Feinberg School of Medicine Northwestern University  Chicago IL 60611 USA"},{"name":"Department of Surgery Northwestern University Feinberg School of Medicine  Chicago IL 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason A.","family":"Wertheim","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department Northwestern University  Evanston IL 60208 USA"},{"name":"Comprehensive Transplant Center Feinberg School of Medicine Northwestern University  Chicago IL 60611 USA"},{"name":"Department of Surgery Northwestern University Feinberg School of Medicine  Chicago IL 60611 USA"},{"name":"Department of Surgery Jesse Brown VA Medical Center  Chicago IL 60612 USA"},{"name":"Chemistry of Life Processes Institute Northwestern University  Evanston IL 60208 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo A.","family":"Ameer","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department Northwestern University  Evanston IL 60208 USA"},{"name":"Department of Surgery Northwestern University Feinberg School of Medicine  Chicago IL 60611 USA"},{"name":"Chemistry of Life Processes Institute Northwestern University  Evanston IL 60208 USA"},{"name":"Simpson Querrey Institute Northwestern University  Chicago IL 60611 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,24]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(02)75332-9"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2011.07.098"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.31074"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.3727\/000000003108747136"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001426"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2015.02.015"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802608783378891"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-4533(02)00010-3"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2008.09.013"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200600230"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.06.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.07.064"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.09.046"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10104375"},{"key":"e_1_2_6_14_1","first-page":"27","volume":"2014","author":"Catto V.","year":"2014","journal-title":"ISRN Vasc. 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