Evaluation of next generation nanocomposite polymer coated stents incorporating stem cell capture technology for enhanced in situ endothelialisation.

在英国，超过300万人患有心血管疾病，导致超过15万人在75岁以下过早死亡。血液流动受限，心脏周围血管堵塞，导致心肌供血中断，导致心肌细胞死亡。缺氧，如果不治疗，可能会导致心肌损伤或死亡，导致心脏病发作或完全心力衰竭。如果不进行治疗，腿部血管的狭窄可能会导致堵塞、截肢和肢体丧失。需要截肢的患者面临生活质量下降和严重残疾。主要目标是根据梗阻程度使用支架恢复至少一条直线血流。支架的应用是使用微创方法进行的。支架是一种使用导管插入的小网状管，当气球充气穿过病变的血管壁时，支架可以同时展开。支架起到支架的作用，打开动脉以恢复血液流动。然而，目前的支架已经引发了严重的医疗问题，这种支架通过局部过敏反应、慢性肿胀(炎症)和血栓(或凝血)的反复发作来释放药物，这需要终生服用抗血小板和血液稀释药物，这些药物会导致不想要的副作用，然后再进行手术。为了克服目前支架植入方面的问题，我们计划利用我们的知识和专业技能，通过开发两种产品来交付新一代支架：1)新型表面涂层，微小颗粒嵌入聚合物或塑料涂层中，称为纳米复合聚合物，2)在涂层中加入捕获抗体(存在于细胞表面)，以从循环血液中捕获干细胞并将其从剪切流中转化为内皮细胞，从而使内皮型细胞覆盖整个心血管系统，以防止血栓形成。这种纳米复合聚合物已经在实验室和动物身上进行了广泛的测试，证明这种聚合物可以潜在地安全地用于人类。例如，我们开发了一系列使用纳米复合材料的外科植入物，并取得了许多成功成果，例如2.5年前世界上第一个合成风管，患者的情况非常好，到目前为止，已经在患者身上进行了6根引流泪道(泪道)的管，使用相同材料的冠状动脉搭桥术已经在心脏医院开始，心脏瓣膜处于临床前。我们已经优化了支架的聚合物涂层，在这项研究中，我们的计划是对涂层支架进行最终评估，并将它们与目前使用的支架进行比较(作为产品1)。临床前动物研究将用于评估它们在人类身上的有效性应用。产品2的开发正处于原则证明阶段。在这里，我们使用包含在聚合物涂层中的抗体(针对血液中的循环干细胞产生)进行初步测试，以从血液中捕获干细胞，并进行测试以获得足够的数据，以申请资助临床前研究。这项建议将使我们能够在与MHRA(英国监管机构)和FDA协商后，测试聚合物涂层支架，为第一人研究做准备。然后，我们将处于有利地位，可以为临床试验申请资金，这些试验可以植入人体。新一代防止血栓形成的纳米复合聚合物涂层支架的开发，以及包括干细胞捕获技术以增强血管内皮细胞数量的技术，将对全球经济产生重大影响，因为受影响的个人将在劳动力大军中活跃更长时间，享受更高质量的生活，并减轻关键医疗资源的压力。

Over 3 million people in the UK suffer from cardiovascular disease causing over 150,000 premature deaths in people under the age of 75. Restriction of blood flow and blockage of blood vessels surrounding the heart leads to interruption of the blood supply to the heart muscle causing heart cells to die. The oxygen shortage, if left untreated can cause damage or death of the heart muscle resulting in heart attack or complete heart failure. Narrowing of the blood vessels in the legs can lead to blockage, amputation and limb loss if left untreated. Patients requiring amputation face a diminished quality of life and severe disability. The primary goal is to restore at least one straight line of blood flow by using a stent depending on the degree of obstruction. The application of stenting is carried out using a minimally invasive approach. A stent is a small mesh tube that is inserted using a catheter, and is deployed at the same time as a balloon is inflated across the diseased vessel wall. The stent acts as a scaffold to hold open the artery to restore blood flow. However, severe healthcare concerns have been raised with current stents, which release drugs through localised allergic reactions, chronic swelling (inflammation) and repeat episodes of thrombosis (or blood clotting), which requires a lifetime prescription of anti-platelet and blood thinning medication causing unwanted side effects followed by repeat surgery. To overcome the current problems with stenting, we plan to build upon our knowledge and expertise to deliver a new generation of stents by developing two products: 1) a novel surface coating with tiny particles embedded in a polymer or plastic coating called nanocomposite polymers, and 2) inclusion of capture antibodies (present on the surface of cells) in to the coating layer to capture stem cells from the circulating blood and converting it to endothelial cells from shear flow, the endothelial is type cells cover entire our cardiovascular system , to protect from blood thrombosis. The nanocomposite polymers have already undergone extensive testing in the laboratory, and in animals demonstrating that the polymer can be potentially used safely in humans. For example, we developed a range of surgical implants using nanocomposite polymers with a number of successful outcomes, such as the world's first synthetic wind pipe over 2.5 years ago and the patient is doing very well, 6 tubes that drain the tears (lacrimal duct) have been carried out in patients to date, and coronary artery bypass graft using same materials has started at Heart Hospital, heart valves at the preclinical. We have already optimised the polymer coating for stents, and in this study our plan is to carry out a final assessment of coated stents and compare them with currently used stents (as product 1). Pre-clinical animal studies will be used to evaluate their effectiveness application in humans. The development of product 2 is at the proof-of-principle stage. Here, we carry out preliminary tests using antibodies (raised against circulatory stem cells in the blood) incorporated in to the polymer coating for capturing stem cells from the blood, and perform tests to obtain sufficient data to apply for funding towards pre-clinical studies. This proposal will enable us to test polymer coated stents in preparation for first-in-man studies after consultation with the MHRA (UK regulatory agencies) and FDA. We will then be in a strong position to apply for funding towards clinical trials, which can be implanted in humans. The development of a new generation of nanocomposite polymer coated stents, which prevent thrombosis along with the inclusion of stem cell capture technology to enhance endothelisationcells would have a significant impact on the global economy, as individuals affected will be active in the workforce for longer, enjoy a greater quality of life and reduce the strain on vital healthcare resources.