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

Lee Y, Le Thi P, Seon GM, Ryu SB, Brophy CM, Kim Y, Park JC, Park KD, Cheung-Flynn J, Sung HJ
J Control Release. 2017 266: 321-330

PMID: 28987880 · PMCID: PMC5723561 · DOI:10.1016/j.jconrel.2017.10.002

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.

Copyright © 2017 Elsevier B.V. All rights reserved.

MeSH Terms (14)

Animals Anticoagulants Cell Movement Cell Proliferation Heparin Humans Myocytes, Smooth Muscle Neointima Peptides Platelet Adhesiveness Polyesters Rats, Sprague-Dawley Saphenous Vein Thrombosis

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