球型支架的開發與實驗驗證

Abstract

顱內動脈瘤為血管壁弱化導致局部病理性擴張的腦血管疾病，破裂會造成嚴重併發症甚至猝死。顱內動脈瘤治療的標準方法為開顱手術及白金線圈栓塞術。另外，肝癌為現今全球第六大癌症，死亡人數在所有癌症中排名第三，肝癌的其中一項療法是利用栓塞肝動脈來阻斷供應癌細胞的血流。本研究提出一項或能適用於此兩項疾病的微型醫療器材─球型支架，它能夠降低通過患部的血流量，在顱內動脈瘤的應用中，球型支架可以阻斷血流流入動脈瘤囊內部，使動脈瘤囊內部的血液流場較為穩定，降低動脈瘤破裂的風險。而在肝癌的應用可以透過部署球型支架於肝動脈的上游，阻斷流至下游癌細胞處的血液，使肝癌細胞沒有養分來源。 本研究流程透過設計、模擬、製造與實驗，開發出三款不同的球型支架，分別為：雷射切削球型支架、雙層編織球型支架以及覆膜球型支架。首先是設計方面，藉由CAD軟體，訂定出設計參數並繪製出雷射切削以及雙層編織球型支架；接著是模擬方面，以有限元素模型分析球型支架在製造及臨床上的機械性質，以確認球型支架在製造及臨常上不會造成材料破壞；再來為製造方面，雷射切削支架以鎳鈦合金無縫微管進行雷射切削加工，透過熱處理後，施以噴砂以及拋光處理製得，雙層編織球型支架則將鎳鈦絲線進行編織後，再透過熱處理成雙層球狀並且以焊接工藝製成，而覆膜球型支架則是將雷射切削球型支架作為骨架，以靜電紡絲技術在雷射切削球型支架上進行覆膜，再施以真空燒結以提升膜的防水性及機械性質；最後是實驗方面，三款球型支架皆進行釋放實驗以及流量實驗，以檢測其臨床行為。在釋放實驗方面，三款球型支架皆能成功壓縮至導管內，亦成功在血管中自動回彈成球狀；在流量實驗方面，雷射切削、雙層編織以及覆膜球型支架分別阻擋了30 - 40 %、50 - 60 %、100 %的血液流量，顯示出球型支架符合現行臨床所需。

An intracranial aneurysm is a cerebrovascular disorder in which structural weakening of the wall media causes localized pathological dilation of the blood vessel. As an aneurysm ruptures, it may lead to severe complications or even sudden death. The standard treatments for intracranial aneurysms include traditional craniotomy and endovascular coiling. In addition, Liver cancer is the sixth common cancer in the world and is the third leading cause of cancer death in Taiwan. One of the treatment options is hepatic artery embolization. In this research, an implantable medical device, spherical stent, is proposed. By directly deploying spherical stent inside the aneurysm, the device is able to reduce the blood flow into aneurysm, which makes the blood flow inside the aneurysm relatively stable. Also, by deploying spherical stent in the upstream hepatic artery, it can cut down the blood supply to cancer cells in the downstream. Through the design, simulation, manufacturing and experiment processes, this research develop three different kinds of spherical stents: laser-cutting spherical stent, double-layered braided spherical stent and covered spherical stent. In the design step, laser-cutting and double-layered braided spherical stents were design with CAD software. In the simulation step, the finite element model was developed to analyze the mechanical behavior of the devices during manufacturing and deployment processes to confirm if the spherical stents will damage or not. In the manufacturing step, laser-cutting technology was used on nitinol seamless tubes, followed by heat treatments and polishing to make the laser-cutting spherical stent. The double-layered braided spherical stent was manufactured on nickel-titanium filaments with braided technology and then heat-treated the device into the double-layered shape. Covered spherical stent was laser-cutting spherical stents covered with waterproof membranes. Electrospinning technique was applied on the laser-cutting spherical stent to produce membranes outside the device, followed by vacuum-sintering process to improve the waterproof property and mechanical behavior of membranes. In the experiment step, all three spherical stents were subjected to release and flow experiments to verify clinical performance. Results of release experiments show that the three kinds of spherical stents can be successfully compressed into catheters and successfully rebounded into the original spherical shape in blood vessels. On the other hand, results of flow experiments show that the laser-cutting, double-layered braided and the covered spherical stents blocked blood flow about 30-40 %、50-60 % and 100 %, respectively.