RESUMEN
Regarding the high requirement of cardiac and vascular implants in tissue engineering, a novel concept of surface chemistry strategy featuring multiple functions is proposed in this study, which provides glutathione peroxidase (GPx)-like catalytic activity and allows secondary reactions for grafting functional biomolecules. The suggested strategy is the fabrication of a metal-catechol-(amine) network (MCAN) containing copper ions with GPx-like activity, amine-bearing hexamethylenediamine (HD) and wet adhesive catechol dopamine (DA). With a simple one-step molecular/ion co-assembly, the developed copper-DA-HD (CuII-DA/HD) network can be used to catalyze the generation of therapeutic nitric oxide (NO) gas in a durable and dose-controllable manner. The primary amine groups in the CuII-DA/HD network facilitate the secondary immobilization of bivalirudin (BVLD) to further provide an antithrombotic activity as supplement to the functions of NO. The CuII-DA/HD + BVLD coating functionalized on cardiovascular stents successfully improved thromboresistance, anti-restenosis, and promotes re-endothelialization in vivo. With regard to the ease of operation and low cost, the synergetic modification using MCAN strategy is of great potential for developing multifunctional blood-contacting materials/devices.
Asunto(s)
Catecolaminas , Materiales Biocompatibles Revestidos , Catálisis , Células Endoteliales de la Vena Umbilical Humana , MetalesRESUMEN
Specific selectivity of vascular cells and antithrombogenicity are crucial factors for the long-term success of vascular implants. In this work, a novel concept of mussel-inspired "built-up" surface chemistry realized by sequential stacking of a copper-dopamine network basement, followed by a polydopamine layer is introduced to facilitate the combination of nitric oxide (NO) catalysis and vascular cell selectivity. The resultant "built-up" film allowed easy manipulation of the content of copper ions and the density of catechol/quinone groups, facilitating the multifunctional surface engineering of vascular devices. For example, the chelated copper ions in the copper-dopamine network endow a functionalized vascular stent with a durable release of NO via catalytic decomposition of endogenous S-nitrosothiol. Meanwhile, the catechol/quinone groups on the film surface allow the facile, secondary grafting of the REDV peptide to develop a selectivity for vascular cells, as a supplement to the functions of NO. As a result, the functionalized vascular stent perfectly combines the functions of NO and REDV, showing excellent antithrombotic properties and competitive selectivity toward the endothelial cells over the smooth muscle cells, hence impressively promotes re-endothelialization and improves anti-restenosis in vivo. Therefore, the first mussel-inspired "built-up" surface chemistry can be a promising candidate for the engineering of multifunctional surfaces.
Asunto(s)
Materiales Biocompatibles Revestidos , Óxido Nítrico , Catálisis , Células Endoteliales de la Vena Umbilical Humana , Miocitos del Músculo Liso , Propiedades de SuperficieRESUMEN
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.