期刊
LANGMUIR
卷 32, 期 20, 页码 5038-5047出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.6b00524
关键词
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资金
- National Institutes of Health [NIH R01 HL107913]
- National Science Foundation Graduate Research Fellowship [NSF DGE-1433187]
Although drug-eluting stent technologies have significantly improved clinical outcomes over the past decade, substantial issues with postimplantation vessel reocclusion still remain. To combat these issues, bioactive amphiphilic macromolecules (AMs), comprised of a functional end group, a branched hydrophobic domain, and a hydrophilic poly(ethylene glycol) tail, were investigated as a therapeutic coating to reduce smooth muscle cell (SMC) proliferation and platelet adhesion. In this study, grafting-from and grafting-to approaches for AM surface functionalization were compared to determine the effects of fabrication method on bioactive delivery characteristics, including the AM loading, release, and biological activity. Grafted-from coatings were formed by stepwise synthesis of phosphonate AMs, 1pM, on the substrate, first by alkyl phosphonate coordination to stainless steel and subsequent carbodiimide coupling to conjugate the hydrophobic and hydrophilic domains. In contrast, grafted-to monolayers were assembled utilizing presynthesized 1pM in a tethering by aggregation and growth technique. Coatings formed using the grafting-from approach yielded high AM grafting density and a highly ordered layer, which corresponded to a slower release rate and sustained bioactivity over 28 days. In contrast, the grafted to coatings yielded less dense, heterogeneous layers, which released faster and were therefore less efficacious in suppressing prolonged SMC proliferation. Both coatings significantly reduced platelet adhesion compared to an uncoated control, but similar platelet adhesion results between grafted-from and grafted-to coatings suggest that both surfaces maintained a molecular density favorable for antiplatelet activity. Overall, the grafting-from method produced uniform coatings with improved loading, release, and bioactive properties compared to the grafting-to approach, highlighting the potential of AM controlled release coatings for therapeutic delivery.
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