ICF Mechanical Property Optimisation of Magnesium Alloy Wires for Bioresorbable Vascular Scaffolds for the Treatment of Peripheral Arterial Disease

本项目旨在开发一种新型镁-锂-钇合金丝，该合金丝具有制造用于治疗外周动脉疾病（PAD）的生物可吸收血管支架（BVS）医疗器械所需的最佳机械性能。通过改变合金成分、工艺温度和拉丝和成形过程中的应变速率，本项目将研究如何产生更有利的显微组织，以获得最佳的机械性能和成本效益。这项工作将与中小企业公司Lumenology密切合作进行，Lumenology将把获得的知识应用到其BVS器械的制造过程中。BVS是一种新兴技术，可解决有效治疗PAD的未满足临床需求。对于最佳治疗方法没有达成共识，因为开放手术、血管内介入或混合策略都有明显的缺点。因此，PAD患者的前景很差，严重的PAD患者如果不截肢，5年死亡率高达65%.1PAD主要由动脉粥样硬化引起的狭窄和损伤导致血流受限。动脉粥样硬化通常用血管成形术（球囊导管）和永久性金属支架治疗。球囊导管迫使阻塞的动脉开放，支架在动脉愈合的同时提供结构。支架被压缩到球囊导管输送系统上，通过动脉输送到阻塞处，并膨胀到更大的直径。最小化压缩装置/球囊系统直径是确保容易输送和安全扩张的关键。目前的支架对治疗冠状动脉是有效的，但是对于长PAD病变，特别是在膝盖以下的动脉（BTK）中，实施与动脉早期再闭塞和支架断裂有关。临时BVS器械是治疗BTK动脉的潜在解决方案。BVS必须提供等同于支架的急性结构支撑，以扩大并允许动脉愈合，但随后被安全吸收，消除与永久支架相关的长期并发症。镁合金是临时BVS器械最有前途的候选材料，因为它们具有适当的机械性能，同时在适当的时间范围内安全降解。镁合金的一个局限性是，与永久支架中使用的材料相比，它们表现出相对较差的延展性。因此，目前的镁基BVS器械与永久支架相比具有更大的输送直径。镁合金的机械性能受合金微观结构的强烈影响。实验室测试表明，Lumenology当前的BVS器械表现出令人印象深刻的机械性能。然而，在成形过程中，内部微观结构显著变形，降低了延展性，从而限制了可实现的最小压实直径。本项目旨在通过在器件制造过程中修改合金成分和工艺条件来调节微观结构的特性，从而改善镁锂钇合金丝的延展性。这将使基于镁合金丝的BVS装置的全部潜力得以释放，为PAD的治疗带来革命性的变化。如果成功，Lumenology的BVS装置具有优化的微观结构和机械性能，将能够被压缩到更小的直径，使其更容易和更安全地输送到患病的动脉中。减小器械/球囊系统的直径将有助于成功进行首次人体临床试验。这将使Lumenology能够将该设备推向市场，开始治疗数百万患有PAD的患者，这些患者目前的治疗选择有限，死亡风险增加。

This project aims to develop a novel magnesium-lithium-yttrium alloy wire with the optimum mechanical properties required for manufacture of bioresorbable vascular scaffold (BVS) medical devices for the treatment of peripheral artery disease (PAD). Through altering the alloy composition, process temperature and strain rate during wire drawing and forming, this project will investigate how a more favourable microstructure can be generated for optimum mechanical properties with cost effectiveness. The work will be conducted in close collaboration with SME company Lumenology who will apply the knowledge gained into the manufacturing processes of their BVS device.BVS are an emerging technology which address an unmet clinical need for an effective treatment of PAD. There is no consensus on the best treatment approach because open surgery, endovascular interventions, or hybrid strategies all have significant drawbacks. Thus the outlook for patients with PAD is poor, and, without limb amputation in severe cases of PAD, the 5-year mortality rate is as high as 65%.1PAD is mainly caused by atherosclerosis causing narrowing and damage leading to restricted blood flow. Atherosclerosis is generally treated with angioplasty (balloon catheters) and permanent metallic stents. Balloon catheters force open blocked arteries and stents provide structure while the artery heals. Stents are compacted onto balloon catheter delivery systems, fed through the arteries to the blockage and inflated to a larger diameter. Minimisation of the compacted device/balloon system diameter is key to ensure easy delivery and safe expansion.Current stents are effective for treating the coronary arteries, however implementation for long PAD lesions, particularly in arteries below-the-knee (BTK), has been associated with arteries re-occluding early and stent breakages. Temporary BVS devices are a potential solution for the treatment of BTK arteries. A BVS must provide acute structural support equivalent to stents to widen and allow the artery to heal but subsequently be safely absorbed, removing the long-term complications associated with permanent stents.Magnesium alloys are the most promising candidate material for temporary BVS devices because they have appropriate mechanical properties whilst degrading safely, within a suitable timeframe. One limitation of magnesium alloys is that they exhibit relatively poor ductility compared to the materials used in permanent stents. Consequently, current magnesium based BVS devices have larger delivery diameters compared to permanent stents.The mechanical properties of magnesium alloys are strongly influenced by the alloy's microstructure. Benchtop testing demonstrates that Lumenology's current BVS device exhibits impressive mechanical performance. However, during forming, the internal microstructure is significantly deformed, reducing ductility and thus limiting the minimum achievable compaction diameter.This project aims to improve the ductility of magnesium-lithium-yttrium alloy wire by regulating the characteristics of the microstructure through modifying the alloy composition and processing conditions during device manufacture. This will allow the full potential of magnesium alloy wire based BVS devices to be unlocked, opening the door to revolutionising the treatment of PAD.If successful, Lumenology's BVS device with optimised microstructure and mechanical properties will be able to be compacted to smaller diameters making it easier and safer to deliver into diseased arteries. Reduction of the diameter of the device/balloon system will be instrumental in progressing towards a successful first in-human clinical trial. This would allow Lumenology to bring the device to the market to start treating the millions of patients suffering from PAD who currently have limited treatment options and increased risk of death.