Dai Sheng, Jiang Lang, Liu Luying, Chen Jiang, Liao Yuzhen, He Shuang, Cui Jiawei, Liu Xiaoqi, Zhao Ansha, Yang Ping, Huang Nan
Institute of Biomaterials and Surface Engineering, Key Lab. for Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, No. 111 of the North 1st Section of Second Ring Road, Chengdu 610031, China.
National Engineering Research Center for Biomaterials, Sichuan University, No. 29 of Wangjiang road, Wuhou district, Chengdu, Sichuan 610064, China.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2038-2049. doi: 10.1021/acsbiomaterials.0c00041. Epub 2020 Mar 31.
Implantation of a drug-eluting stent is the most common treatment method for patients with cardiovascular atherosclerosis. However, this treatment may delay re-endothelialization, and the drug polymer-coated stent may induce thrombosis months after a stent implantation. The development of polymer-free drug-eluting stents is a promising approach to overcome these shortcomings. Titanium dioxide nanotubes (TiO-NTs) are excellent drug carriers and have been considered as a potential material for polymer-free drug-eluting stents. However, TiO-NTs reportedly induce severe blood clotting, which is a significant shortcoming for use as a stent. Vascular stents must be compatible with blood and must have antibacterial, anti-inflammatory, and selective inhibitory activities in the abnormal hyperplasia of smooth muscle cells, instead of delaying the re-endothelialization of endothelial cells. To meet these requirements, we presented a composite material that featured ultraviolet (UV) irradiation of TiO-NTs-containing silver nanoparticles (AgNPs). The AgNPs were loaded in the lumen of TiO-NTs as a representative compound to suppress the inflammatory response and hyperplasia. UV irradiation was performed as a novel method to improve the anticoagulant ability of the AgNP-loaded TiO-NTs. The chemical state and biocompatibility of the UV-TiO-NTs@AgNPs were evaluated. UV irradiation strongly improved the anticoagulant ability of the TiO-NTs and moderated the release of Ag from AgNPs, which selectively suppressed the inflammatory response and hyperplasia. Furthermore, the UV-TiO-NTs@AgNPs-2 displayed enhanced biocompatibility evidenced by the inhibition of platelet adhesion, bactericidal activity, selective suppression of the smooth muscle cell proliferation, and inhibition of the adhesion of macrophages. The collective findings indicate the potential of the photofunctionalized TiO-NTs loaded with AgNPs as a material for polymer-free drug-eluting stents.
植入药物洗脱支架是心血管动脉粥样硬化患者最常用的治疗方法。然而，这种治疗可能会延迟再内皮化，并且药物聚合物涂层支架可能在支架植入数月后诱发血栓形成。无聚合物药物洗脱支架的开发是克服这些缺点的一种有前途的方法。二氧化钛纳米管（TiO-NTs）是优异的药物载体，已被视为无聚合物药物洗脱支架的潜在材料。然而，据报道TiO-NTs会引发严重的血液凝固，这是用作支架的一个重大缺点。血管支架必须与血液相容，并且在平滑肌细胞异常增生时必须具有抗菌、抗炎和选择性抑制活性，而不是延迟内皮细胞的再内皮化。为了满足这些要求，我们提出了一种复合材料，其特点是对含银纳米颗粒（AgNPs）的TiO-NTs进行紫外线（UV）照射。将AgNPs作为代表性化合物加载到TiO-NTs的管腔中以抑制炎症反应和增生。紫外线照射作为一种新方法来提高负载AgNP的TiO-NTs的抗凝能力。评估了UV-TiO-NTs@AgNPs的化学状态和生物相容性。紫外线照射极大地提高了TiO-NTs的抗凝能力，并减缓了Ag从AgNPs中的释放，从而选择性地抑制了炎症反应和增生。此外，UV-TiO-NTs@AgNPs-2表现出增强的生物相容性，这通过抑制血小板粘附、杀菌活性、选择性抑制平滑肌细胞增殖以及抑制巨噬细胞粘附得到证明。这些研究结果共同表明，负载AgNPs的光功能化TiO-NTs作为无聚合物药物洗脱支架材料具有潜力。
