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Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity

Authors
 Yunki Lee  ;  Phuong Le Thi  ;  Gyeung Mi Seon  ;  Seung Bae Ryu  ;  Colleen M. Brophy  ;  YongTae Kim  ;  Jong-Chul Park  ;  Ki Dong Park  ;  Joyce Cheung-Flynn  ;  Hak-Joon Sung 
Citation
 Journal of Controlled Release, Vol.266 : 321-330, 2017 
Journal Title
 Journal of Controlled Release 
ISSN
 0168-3659 
Issue Date
2017
Keywords
Anti-thrombosis ; Heparin ; Intimal hyperplasia ; MK2 inhibitory peptide ; Synthetic vascular grafts ; Tyrosinase-triggered surface functionalization
Abstract
The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92-272μg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti-neointimal activity of synthetic vascular grafts.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/161403
DOI
10.1016/j.jconrel.2017.10.002
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
박종철(Park, Jong Chul) ; 성학준(Sung, Hak-Joon)
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Full Text
https://www.sciencedirect.com/science/article/pii/S0168365917308891
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