金屬奈米銅Phema混成複合材料之血液相容性改質研究

Abstract

由於各種臨床顯微手術的突飛猛進，以及人工器官研發的蓬勃發 展，具有血液相容功能之生物醫學材料早已成為不可忽視的重要研究 方向。尤其近年來，不論是心血管疾病所需之支架，或是侵入式藥物 治療手段所需之醫療元件，長時間之抗凝血效果以及生物相容性等問 題，仍有待釐清解決。 在本研究中，我們提出一嶄新的概念，經由金屬銅離子與水膠分 子結構間之偶合反應(coupling interaction), 利用即時(in-situ)光聚合 合成法及化學還原法，可即時合成出具有不同大小均勻之奈米金屬銅 粒子及規則性結構排列，分散在高分子水膠中(pHEMA) 之複合材 料。進而研究此奈米複合材料與血液接觸之界面觸媒作用、電化學特 性，以及奈米銅粒子與pHEMA 之界面性質及反應，目的在於(1) 探 討複合材料之表面物性及化性(2) 研究其抑止凝血蛋白分子吸附及 活化之作用，(3) 同時了解其抑制血小板之貼覆及聚集, 以達到抗凝 血之效果。此外，我們並預期由奈米銅粒子延伸之複合材料之n 型特 性，可更控制及大幅延長抗凝血之作用。

Use of medical devices with clinically acceptable blood compatibility has gained increasing attention over the years. This has been consciously alerted due to a current understanding that the devices used to contact with human blood has been criticized to having insufficient anti-blood clotting surface for short-to-long term invasive medication, which is especially critical for those long-term implants such as cardiovascular stents, pacemaker, etc. and a consequence of stroke risk has been threatened to the patients. Continuing development of anti-blood clotting surface has attracted increasing attention and a number of very recent reports have emphasized the use of polyethylene glycol-derived materials or hydrogels capable of slow releasing anti-coagulants and a catalytic generation of nitric acid through the use of lipophilic Cu(II) complex, showing promising thromboresistant outcomes in-vitro. However, drawbacks such as molecular leaching, reducing agent addition, long-term anti-thrombosis, and biocompability, have been concerns to be considered and solved. In this proposal, we employed a concept by which metallic Cu(0) nanoparticles were embedded into a biocompatible polymeric HEMA matrix using an in-situ photopolymerization followed by an in-situ chemical reduction process, where the use of metallic Cu(0) is expected to provide more electrons (compared to the lipophilic Cu(II) complex) to transfer to blood clotting-induced proteins such as fibrinogen, to inhibit protein adsorption and degradation, and in the meantime, to suppress platelet adhesion and aggregation on the resulting Cu(0)-pHEMA hybrid surface. Composition distribution, surface texture, catalytic and electrochemical characteristics of the hybrid at the interface between blood and hybrid are critical for a better understanding on the mechanism(s) of the anti-clotting behavior. It is also expected the incorporation of metallic Cu can be further enhanced the n-type characteristic of the hybrid, which, together with more electron transfer capability, is highly anticipated to give an enhanced thromboresistant property than neat polymeric matrix, and lipophilic Cu(II) complex-containing system as well.