創新鎳鈦合金血管支架之設計、分析與製造

Abstract

血管支架置放手術已成為治療心肌梗塞的黃金標準，其中鎳鈦合金血管支架被廣泛地運用在人體的周邊血管疾病。血管支架植入人體後，由於長期需承受血流脈動週期性的壓力及人體日常反覆動作，血管支架往往會發生結構性疲勞破壞甚至斷裂，因此，提升其壽命已成為血管支架設計的重要課題。本研究提出一項簡單的血管支架設計概念，可有效增進血管支架之抗疲勞破壞能力。此設計概念原理，乃藉由漸進式調整血管支架之Strut寬度，將血管支架局部所承受集中應力分散並導引至應力承載較低區域，以使能量作更有效分配。為驗證此創新設計概念，本研究以有限元素方法進行模擬與疲勞安全係數計算，結果顯示此設計之疲勞安全係數，大幅躍升至相對應之標準血管支架達5倍以上，對於現今血管支架設計而言是一大突破。 以往鎳鈦合金血管支架的開發流程冗長，即便最細微的設計修正也得耗費大量成本；本研究建立雛型品快速設計及製造流程：CAD參數化設計結合有限元素電腦模擬、雷射切削、定型熱處理、表面噴砂與電解拋光等核心技術能力，大幅降低產品開發週期。透過摻鐿之脈衝式光纖雷射對鎳鈦無縫微管作切削加工，接著利用自行設計之錐形夾具固定血管支架內徑，置於鹽浴爐內進行定型熱處理；最後，血管支架表面先以氧化鋁顆粒做噴砂處理，再透過電解拋光使表面達到鏡面效果。實驗結果顯示，溫度500℃、退火時間200秒，可以達到良好的定型效果；進一步檢驗其材料性質變化，發現相變態溫度(Af)無明顯提升，說明該熱處理參數之可行性。另外實驗亦比較了雷射切削與進行電解拋光後表面改善情形，結果顯示完成電解拋光的血管支架其切削邊緣不僅較為平整，表面粗糙度Ry更從100 nm降至約10 nm，效果十分顯著。最後利用上述製程，完成本文提出之創新鎳鈦合金血管支架雛型品，作為未來產品概念展示。 本研究進一步將錐形Strut血管支架設計概念延伸應用在另一備受矚目的議題：如何提升微型儲藥槽血管支架因加工而損失之抵抗疲勞破壞能力。微型儲藥槽血管支架是未來植入式醫療器材之流行趨勢，它不僅可以作為傳統塗藥血管支架的另一選項，也可以應用於治療癌症之新藥物載具，擁有許多潛在的可能性。 本文提出一項全球首創之菱形式微型儲藥槽血管支架，藉由改變儲藥槽之幾何形狀，使能量作更均勻地分配。此菱形式微型儲藥槽血管支架，藥物承載量為傳統塗藥血管支架7.7倍，且疲勞壽命不減反增，甚至高於無任何加工鑽孔之傳統塗藥血管支架，效果驚人。此設計概念亦榮獲2014德國紅點設計競賽－概念設計獎之國際殊榮。

Vascular stenting has received great attention from the medical community since its introduction. The NiTi self-expanding stent is used to treat peripheral artery diseases; however, after implantation, these stents suffer from various cyclic motions caused by pulsatile blood pressure and daily body activities. Due to this challenging environment, fatigue performance has become a major issue for stent design. In this study, a simple yet intriguing concept of stent design aimed at enhancing pulsatile fatigue life was investigated. The concept of this design is to shift the highly concentrated stresses/strains away from the crown and re-distribute them along the stress-free strut by tapering its strut width. Finite element models were developed to evaluate the mechanical integrity and pulsatile fatigue resistance of the stent to various loading conditions. Simulation results showed that the fatigue safety factor jumped to a whopping 5.4 times that of the standard stent. The findings provide an excellent guide to the optimization of future stent design to greatly improve stent fatigue performance. Conventional NiTi stent design process could take a bunch of time for completion, which is a time-consuming and inefficient process. Therefore, it is important to develop the integrated CAD/FEA/RP (Rapid Prototyping) scheme, as this process could potentially reduce the product development cycle from months to weeks and save precious time for the biomedical industry in the future. The study has developed stent core technologies including parametric design, analysis and manufacturing: NiTi self-expanding stents were first manufactured from seamless hypotubes using Yb-doped pulsed fiber laser, followed by sequential expansions and heat treatments to the target stent diameter using designed fixtures and salt bath furnace. Finally, NiTi stents were abraded with Al2O3 particles by sand-blasting and then further refined by electro-polishing. Experimental results showed that the salt bath temperature of 500oC with annealing time of 200 seconds were able to achieve eligible shape setting rate without the change of transformation temperature Af. Surface finish of NiTi stents improve prominently after eletro-polishing, resulting in the mirror-like surface. A NiTi self-expanding stent of 6-mm diameter and 13-mm long was prototyped for demonstration of our novel stent concept. In recent years, an innovative variation of the drug-eluting stent with micro-sized drug reservoirs (depot stent) has been introduced. It allows programmable drug delivery with both spatial and temporal control and has several potential advantages over conventional drug-eluting stent. However, creating such reservoirs on the stent struts may weaken the structure of the stent scaffolding and compromise its mechanical integrity, especially the stent fatigue life. Such fatigue-related stent issues have thereby drawn much attention within the medical field. A novel rhombus-shaped depot stent to enhance not only the drug dosage but also the stent fatigue life was proposed in this study. The concept can be viewed as an extension of tapered strut stent. By creating the rhombus-shaped reservoirs on the stent struts, a more efficient way to store energy by subjecting a higher volume of the stent structure to the same loading was achieved. The total drug capacity of the proposed rhombus-shaped depot stent could be increased up to 7.7 times, without any tradeoff in its fatigue life. Therefore, this depot stent is the first of its kind and could carry more drugs with longer service life than its drug-eluting stent counterparts, thereby opening up a wide variety of new treatment potentials and opportunities. The genuine design “Superior Stent” has won the international jurors’ appreciation, awarded the 2014 Red Dot Award: Design Concept.