1. Biomimetic engineering endothelium-like coating on cardiovascular stent through heparin and nitric oxide-generating compound synergistic modification strategy
- Author
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Yu Xiao, Nan Huang, Hua Qiu, Jingxia Liu, Ying Yang, Manfred F. Maitz, Pengkai Qi, Zhilu Yang, and Xing Tan
- Subjects
Endothelium ,Cell ,Cystamine ,Biophysics ,Bioengineering ,02 engineering and technology ,engineering.material ,Nitric Oxide ,Cell Line ,Nitric oxide ,Allylamine ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,Coated Materials, Biocompatible ,Coating ,Biomimetics ,In vivo ,Organoselenium Compounds ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,Heparin ,Chemistry ,Drug-Eluting Stents ,021001 nanoscience & nanotechnology ,Actins ,Endothelial stem cell ,medicine.anatomical_structure ,Mechanics of Materials ,Ceramics and Composites ,engineering ,Rabbits ,0210 nano-technology ,medicine.drug - Abstract
Co-immobilization of two or more molecules with different and complementary functions to prevent thrombosis, suppress smooth muscle cell (SMC) proliferation, and support endothelial cell (EC) growth is generally considered to be promising for the re-endothelialization on cardiovascular stents. However, integration of molecules with distinct therapeutic effects does not necessarily result in synergistic physiological functions due to the lack of interactions among them, limiting their practical efficacy. Herein, we apply heparin and nitric oxide (NO), two key molecules of the physiological functions of endothelium, to develop an endothelium-mimetic coating. Such coating is achieved by sequential conjugation of heparin and the NO-generating compound selenocystamine (SeCA) on an amine-bearing film of plasma polymerized allylamine. The resulting surface combines the anti-coagulant (anti-FXa) function provided by the heparin and the anti-platelet activity of the catalytically produced NO. It also endows the stents with the ability to simultaneously up-regulate α-smooth muscle actin (α-SMA) expression and to increase cyclic guanylate monophosphate (cGMP) synthesis of SMC, thereby significantly promoting their contractile phenotype and suppressing their proliferation. Importantly, this endothelium-biomimetic coating creates a favorable microenvironment for EC over SMC. These features impressively improve the antithrombogenicity, re-endothelialization and anti-restenosis of vascular stents in vivo.
- Published
- 2019