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Mechanocompatible Polymer‐Extracellular‐Matrix Composites for Vascular Tissue Engineering
Author(s) -
Jiang Bin,
Suen Rachel,
Wang JiaoJing,
Zhang Zheng J.,
Wertheim Jason A.,
Ameer Guillermo A.
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201501003
Subject(s) - extracellular matrix , intimal hyperplasia , tissue engineering , carbodiimide , fibronectin , biomedical engineering , in vivo , fibrin , materials science , self healing hydrogels , neointimal hyperplasia , chemistry , surgery , polymer chemistry , immunology , biochemistry , medicine , microbiology and biotechnology , smooth muscle , biology , restenosis , stent
Small‐diameter vascular grafts developed from vascular extracellular matrix (ECM) can potentially be used for bypass surgeries and other vascular reconstruction and repair procedures. The addition of heparin to the ECM improves graft hemocompatibility but often involves chemical cross‐linking, 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‐octamethylene citrate)‐ co ‐cysteine is hybridized to the ECM, forming a polymer‐ECM composite that allows for heparin immobilization via maleimide–thiol “click” chemistry. Heparinized composites reduce platelet adhesion by >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‐only control grafts at four weeks. In contrast, grafts that are heparinized with carbodiimide chemistry exhibit increased intimal hyperplasia (4.2‐fold) and increased macrophage infiltration (3.5‐fold) compared to ECM‐only 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.