Thierry Benjamin, Winnik Françoise M, Merhi Yahye, Silver Jim, Tabrizian Maryam
Department of Biomedical Engineering, Mc Gill University, 3775 University Street, Montreal, Que., Canada H3A 2B4.
Biomaterials. 2004 Aug;25(17):3895-905. doi: 10.1016/j.biomaterials.2003.10.068.
Catheter-based brachytherapy is one of the most effective modalities to inhibit hyperplasia following revascularization procedures. Radioactive stents have failed, however, to prevent clinical hyperplasia due to excessive late lumen loss on the edge of the devices. Numerous strategies have been proposed to circumvent the drawbacks of irradiation therapies, such as the use of more appropriate radionuclides or the "hot-end" stents approach. This paper describes versatile radioactive devices obtained by coating plasma functionalized surfaces-stents or catheters-with a hyaluronan (HA)-diethylenetriamine pentaacetic acid (DTPA) conjugate (HA-DTPA) complexed with a gamma or beta radionuclide. Yttrium and indium were used as radionuclide models, due to their suitability for endovascular radiotherapy. X-ray photoelectron microscopy and time-of-flight secondary ions mass spectrometry analyses confirmed the successful immobilization of the HA-DTPA conjugate on both the metallic (NiTi) and polymeric (Teflon) plasma functionalized surfaces. HA-DTPA-coated surfaces were significantly more hydrophilic than bare surfaces (39.5 degrees vs. 67 degrees on NiTi substrate and 29 degrees vs. 128 degrees on Teflon substrate). Therapeutic doses of yttrium and indium were easily loaded onto the surfaces and remained stable over 2 weeks with a radionuclide loss of about 6%. The HA-DTPA-coated Teflon surfaces presented significantly less fibrinogen adsorption than uncoated materials in an in vitro flow model. This approach, which combines the hemocompatibility of HA-coated surfaces and the anti-proliferative effects of an appropriate radiotherapy, constitutes a promising methodology to alleviate the restenosis induced by existing devices.
基于导管的近距离放射疗法是血管重建术后抑制增生的最有效方法之一。然而，放射性支架未能预防临床增生，因为在装置边缘存在过多的晚期管腔丢失。人们已经提出了许多策略来规避放射治疗的缺点，例如使用更合适的放射性核素或“热端”支架方法。本文描述了通过用与γ或β放射性核素络合的透明质酸（HA）-二乙烯三胺五乙酸（DTPA）共轭物（HA-DTPA）涂覆等离子体功能化表面（支架或导管）而获得的多功能放射性装置。钇和铟被用作放射性核素模型，因为它们适用于血管内放射治疗。X射线光电子显微镜和飞行时间二次离子质谱分析证实了HA-DTPA共轭物在金属（NiTi）和聚合物（聚四氟乙烯）等离子体功能化表面上的成功固定。HA-DTPA涂层表面比裸露表面明显更亲水（在NiTi基底上为39.5度对67度，在聚四氟乙烯基底上为29度对128度）。钇和铟的治疗剂量很容易加载到表面上，并在2周内保持稳定，放射性核素损失约为6%。在体外流动模型中，HA-DTPA涂层的聚四氟乙烯表面比未涂层材料的纤维蛋白原吸附明显更少。这种方法结合了HA涂层表面的血液相容性和适当放射治疗的抗增殖作用，构成了一种有前途的方法来减轻现有装置引起的再狭窄。
