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首页> 外文会议>World biomaterials congress >Tailoring of dopamine-coated stainless steel with Cu(Ⅱ)-loaded multifunctional nanoparticles for improving the biocompatibility
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Tailoring of dopamine-coated stainless steel with Cu(Ⅱ)-loaded multifunctional nanoparticles for improving the biocompatibility

机译：负载铜（Ⅱ）的多功能纳米粒子对多巴胺涂层不锈钢的定制，以提高生物相容性

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Introduction: Complications such as thrombus and restenosis continue to be the major limitations for clinical application of cardiovascular devices. Surface modification to provide specific bioactivities and enable the biomaterials to long-term directing intravascular response plays important role in improving the performance and function of cardiovascular devices. Cu(Ⅱ) as the key enzymes co-factor was found recently to stimulate endothelium regeneration effectively. Moreover,Cu(Ⅱ) plays key role in scavenging free radical in blood and enhancing hemangiectasis by catalytic reduction of NO. Take the advantage of specific intermolecular reaction, in this study, a novel Cu(Ⅱ)-loaded heparin/poly-Ⅰ-lysine nanoparticle was prepared and immobilized to cardiovascular material surface to improve the biocompatibility. Materials and Methods: As shown in Fig. 1, poly-dopamine coating was firstly deposited to 316L SS surface; after that, copper chloride solution was mixed with poly-Ⅰ-lysine (PLL) to form Cu(Ⅱ)/PLL complex; then the complex was mixed with heparin solution and Cu(Ⅱ)-loaded nanoparticles were prepared via intermolecular electrostatic interaction. Finally, the nanoparticles were immobilized to dopamine-coated surface. The physicochemical properties of modified surface were characterized, the anticoagulation property and cellular compatibility were evaluated. Fig. 1.(A) Preparation of Cu(Ⅱ)-loaded nanoparticles, (B) dopamine coating deposition and (C) nanoparticles immobilized to material surface. Results and Discussion: According to Fig.2, Cu(Ⅱ)-loaded nanoparticles were immobilized to dopamine-coated surface successfully (Fig.2A). The Cu(Ⅱ) incorporated into the nanoparticle mainly by interacting with the amino group and carbonyl group derived from PLL (Fig.2B). In this study, with the increasing of Cu(Ⅱ) concentration, the absolute value of nanoparticle zeta potential was gradually decreased, which indicated the stability was decreased and particle agglomeration may occur. Besides, the increasing of Cu(Ⅱ) concentration may reduce the amino group exposing density and thereby bring down the particle binding amount (Fig.2C). The nanoparticles modified surface displayed favorable Cu(Ⅱ) sustained release property, as well as NO catalytic ability (Fig.2D and E). Biocompatibility evaluation result indicated that the nanoparticle modified surface displayed favorable anti-coagulation and anti-restenosis effect (Fig.2F and H). However, when the Cu(Ⅱ) concentration was less than 0.5 mM, the modified surface may inhibit endothelial cells (ECs) growthing due to the high nanoparticle binding density. When the Cu(Ⅱ) concentration was greater than 2.5 mM, the particle binding density was too little to direct ECs behavior. The nanoparticle modified surface displayed favorable ECs compatibility when Cu(Ⅱ) concentration in the range of 0.5-2.5 mM (Fig.2G). Fig. 2.(A) AFM images of nanoparticles modified surface, (B) FTIR spectra of nanoparticles modified surface, (C) quantitative characterization of heparin and amine exposing density, (D) Cu(Ⅱ) release assay, (E) NO catalytic property, (F) platelet adhesion result, (G) ECs and (H) SMCs growthing profile on different sample surfaces. Conclusions: This study provide a novel construction method of Cu(Ⅱ)-loaded nano-coating. The size, stability, and binding density of nanoparticles was closely related to Cu(Ⅱ) concentration. In a certain Cu(Ⅱ) concentration range, the nano-coating displayed adequate stability and was found to selectively prevent thrombus and restenosis, while promote ECs growthing. This work may provide a promising approach for cardiovascular materials surface modification.
机译：简介：诸如血栓和再狭窄等并发症仍然是心血管器械临床应用的主要局限性。表面修饰可提供特定的生物活性，并使生物材料能够长期指导血管内反应，在改善心血管装置的性能和功能方面起着重要作用。最近发现Cu（Ⅱ）作为关键的酶辅助因子可以有效地刺激内皮细胞的再生。此外，Cu（Ⅱ）通过催化还原NO清除血液中的自由基并增强血管扩张作用，起着关键作用。利用特异性分子间反应的优势，本研究制备了一种新型的负载铜（Ⅱ）的肝素/聚Ⅰ-赖氨酸纳米粒子并将其固定在心血管材料表面，以提高其生物相容性。材料和方法：如图1所示，首先在316L SS表面沉积聚多巴胺涂层;然后在316L不锈钢表面沉积聚多巴胺涂层。然后，将氯化铜溶液与聚Ⅰ-赖氨酸（PLL）混合形成Cu（Ⅱ）/ PLL配合物。然后将复合物与肝素溶液混合，并通过分子间静电相互作用制备负载铜（Ⅱ）的纳米粒子。最后，将纳米颗粒固定在多巴胺涂层的表面上。表征了改性表面的理化性质，评价了其抗凝性能和细胞相容性。图1.（A）负载Cu（Ⅱ）的纳米颗粒的制备，（B）多巴胺涂层沉积和（C）固定在材料表面的纳米颗粒。结果与讨论：根据图2，将负载有Cu（Ⅱ）的纳米颗粒成功地固定在多巴胺涂层表面上（图2A）。 Cu（Ⅱ）主要通过与PLL衍生的氨基和羰基相互作用而掺入纳米颗粒中（图2B）。本研究中，随着Cu（Ⅱ）浓度的增加，纳米粒子ζ电势的绝对值逐渐降低，表明其稳定性下降，可能发生粒子团聚。此外，Cu（Ⅱ）浓度的增加可能会降低氨基的暴露密度，从而降低颗粒的结合量（图2C）。纳米粒子修饰的表面表现出良好的Cu（Ⅱ）缓释性能，以及NO的催化能力（图2D和E）。生物相容性评价结果表明，纳米颗粒改性的表面表现出良好的抗凝和抗再狭窄作用（图2F和H）。然而，当Cu（Ⅱ）的浓度小于0.5 mM时，由于高的纳米粒子结合密度，修饰的表面可能会抑制内皮细胞（ECs）的生长。当Cu（Ⅱ）的浓度大于2.5 mM时，颗粒的结合密度太小，无法指导EC的行为。当Cu（Ⅱ）的浓度在0.5-2.5 mM范围内时，纳米粒子改性的表面表现出良好的ECs相容性（图2G）。图2.（A）纳米粒子修饰表面的AFM图像，（B）纳米粒子修饰表面的FTIR光谱，（C）肝素和胺暴露密度的定量表征，（D）铜（Ⅱ）释放测定，（E）NO催化性能，（F）血小板粘附结果，（G）EC和（H）SMC在不同样品表面上的生长曲线。结论：本研究提供了一种新型的负载Cu（Ⅱ）纳米涂层的方法。纳米粒子的大小，稳定性和结合密度与Cu（Ⅱ）浓度密切相关。在一定的Cu（Ⅱ）浓度范围内，纳米涂层具有足够的稳定性，可以选择性地防止血栓和再狭窄，同时促进ECs的生长。这项工作可能为心血管材料的表面改性提供一种有前途的方法。

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