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Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly- l -lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair. Many functional factors that promote the biological behavior of ECs have been widely used in stent surface modification. To explore the synergistic effect of biological factors and metal ions on the function of microenvironment. This article will introduce important biological function factors (SDF-1α, VEGF) and important metal ions (Zn2+) into the surface. Studies have shown that the combination of the different factors can not only effectively regulate cellular inflammatory response, but also selectively regulate cell biological behavior. Meanwhile, NPV-Zn had excellent biological functions in vitro and in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary artery disease is a great threat to human health and is the leading killer worldwide. Percutaneous coronary intervention is the most effective therapy; however, thrombus, and restenosis caused by endothelium injury continue to be problematic after treatment. It is widely accepted that surface biofunctional modification to improve blood compatibility and accelerate endothelialization may be an effective approach to prevent the occurrence of adverse cardiac events. In this study, novel VEGF-loaded heparin/poly- l-lysine (Hep/PLL) particles were developed and immobilized on a dopamine coated titanium surface. The size, distribution, zeta potential, and morphology of the prepared particles were subsequently characterized. The influence of changes in the surface physicochemical properties after particle immobilization was assessed for blood compatibility and cytocompatibility. Surface-modified VEGF-loaded particles significantly inhibited platelet adhesion and activation and were effective in promoting the proliferation and survival of endothelial progenitor cells and endothelial cells. Moreover, Hep/PLL particles were also beneficial for controlling the long-term release of VEGF, which may facilitate endothelium regeneration. In conclusion, VEGF-loaded Hep/PLL particles were successfully immobilized on the Ti surface, and the biocompatibility was significantly improved. This study demonstrates a potential application for the multifunctional modification of stent surfaces for clinical use. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2024-2034, 2015. [ABSTRACT FROM AUTHOR]

The endothelialization of the metal surface of vascular stents came into focus as a new method for improving the biocompatibility of intravascular stents. This article has its focus on building a biofunctional layer on the activated titanium surface with anti-CD34 antibody, vascular endothelial growth factor (VEGF), and heparin by a layer-by-layer (LBL) self-assembly technique, to promote the endothelialization of the surface. When compared with titanium surface, the number of adhered endothelial progenitor cells (EPCs) on LBLs increased 47.1% after 5 days culture, meanwhile the proliferation rate of EPCs on LBLs during 5 days culture also exhibit significantly improvement. The results of blood compatibility evaluation clearly show that the LBLs reduce the number of adhered and activated blood platelets (adhered: Ti 83% vs. LBL <20% and activated: Ti 57% vs. LBL 19%), and the activated partial thromboplastin time of the LBL surface prolonged about 20 s in compared with platelet-poor plasma. The assembled LBL thus improves the thromboresistance of the titanium surface. The presented biofunctional multilayer of anti-CD34, VEGF, and heparin on titanium can significantly improve the blood compatibility and the endothelialization of a medical device. The biofunctional layer supports generation of a new endothelium onto titanium surface by capturing EPCs and oriented differentiation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013. [ABSTRACT FROM AUTHOR]

Late thrombus and restenosis caused by delayed endothelialization and insufficient biocompatibility of polymer coating continue to be the greatest limitations of drug-eluting stents. In this study, based on the specific structure of vascular basement membrane, a novel biomimetic nano-coating was constructed by incorporating laminin into electrostatic-assembled heparin/poly- l -lysine nanoparticles. Alteration of heparin and poly- l -lysine concentration ratio in a certain range has no significantly influence nanoparticle size, uniformity and stability, but may affect the chemical property and subsequently the binding efficiency to dopamine-coated titanium surface. By use of this feature, four different nanoparticles were synthesized and immobilized on titanium surface for creating gradient nanoparticle binding density. According to in vitro biocompatibility evaluation, the nanoparticle modified surfaces were found to effectively block coagulation pathway and reduce thrombosis formation. Moreover, NP10L and NP15L modified surface with relatively low heparin exposing density (4.9 to 7.1 μg/cm2) showed beneficial effect in selective promoting EPCs and ECs proliferation, as well as stimulating cell migration and NO synthesis. [ABSTRACT FROM AUTHOR]

The biocompatibility of currently used coronary artery stent is still far from perfect, which closely related to insufficient endothelialization and thrombus formation. In this study, heparin, fibronectin and VEGF were immobilized on Ti surface to construct a multifunctional microenvironment with favorable properties to inhibit thrombosis formation and promote endothelialization simultaneously. The microenvironment on Ti surface was characterized in detail and demonstrated that the Hep/Fn/VEGF biofunctional coating was constructed successfully on Ti surface. The influence of surface properties such as chemical composition, roughness, hydrophilicity, and binding density of biomolecules on the performances of hemocompatibility and cytocompatibility was evaluated and discussed. Modified surface significantly enhanced the AT III binding density and prolonged the clotting time. In vitro platelet adhesion and activation assays further proved that the modified surface presented favorable anti-coagulant property. In addition, the proliferation of endothelial progenitor cells (EPCs) and endothelial cells (ECs) on the Hep/Fn/VEGF biofunctional coating was significantly promoted. In conclusion, the Hep/Fn/VEGF biofunctional coating was successfully constructed with desirable anticoagulant and endothelialization supporting properties. This work may provide a promising approach for biofunctional surface modification of coronary artery stent to acquire a desired multifunctional microenvironment. [ABSTRACT FROM AUTHOR]