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

评估结合干细胞捕获技术增强原位内皮化的下一代纳米复合聚合物涂层支架。

• 批准号: EP/L024713/1
• 负责人: Brian G Cousins
• 金额: $ 93.33万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL024713%2F1
• 关键词: Evaluation; next; generation; nanocomposite; polymer

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.

在英国，超过300万人患有心血管疾病，导致超过15万75岁以下的人过早死亡。血液流动的限制和心脏周围血管的阻塞导致心脏肌肉的血液供应中断，导致心脏细胞死亡。缺氧，如果不及时治疗，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。腿部血管的狭窄如果不及时治疗会导致阻塞、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。主要目标是根据阻塞程度使用支架恢复至少一条直线的血流。支架植入术的应用是使用微创方法进行的。支架是使用导管插入的小网状管，并且在球囊膨胀穿过患病血管壁的同时展开。支架作为一个支架来保持动脉开放，以恢复血液流动。然而，目前的支架已经引起了严重的医疗保健问题，其通过局部过敏反应、慢性肿胀（炎症）和血栓形成（或血液凝固）的重复发作释放药物，这需要终生处方抗血小板和血液稀释药物，导致不希望的副作用，随后进行重复手术。为了克服目前支架植入的问题，我们计划利用我们的知识和专业知识，通过开发两种产品来提供新一代支架：1）具有嵌入在聚合物或塑料涂层中的微小颗粒的新型表面涂层，称为纳米复合聚合物，和2）包含捕获抗体（存在于细胞表面上）进入涂层以从循环血液中捕获干细胞并将其从剪切流转化为内皮细胞，内皮细胞是覆盖整个心血管系统的一类细胞，以防止血栓形成。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，证明该聚合物可以安全地用于人类。例如，我们开发了一系列使用纳米复合聚合物的外科植入物，取得了许多成功的成果，如世界上第一个合成风管超过2.5年前和病人做得很好，6管引流眼泪迄今为止，已经在患者中进行了泪道移植，并且心脏医院已经开始使用相同材料进行冠状动脉旁路移植术，临床前的心脏瓣膜。我们已经优化了支架的聚合物涂层，在本研究中，我们的计划是对涂层支架进行最终评估，并将其与目前使用的支架（产品1）进行比较。临床前动物研究将用于评价其在人体中的有效性。产品2的开发正处于原理验证阶段。在这里，我们使用结合到聚合物涂层中的抗体（针对血液中的循环干细胞）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，以申请临床前研究的资金。该提案将使我们能够在与MHRA（英国监管机构）和FDA协商后测试聚合物涂层支架，为首次人体研究做准备。然后，我们将处于有利地位，申请临床试验的资金，这些试验可以植入人体。新一代纳米复合聚合物涂层支架的开发将对全球经济产生重大影响，因为受影响的个人将更长时间地活跃在劳动力队伍中，享受更高的生活质量，并减少对重要医疗资源的压力，这种支架沿着防止血栓形成，并包含干细胞捕获技术以增强内皮细胞的增殖。

项目成果

Development of pre-polymer coatings with pro-endothelialisation potential for cardiovascular devices

开发用于心血管装置的具有促内皮化潜力的预聚物涂层

• 发表时间: 2016
• 作者: Pang, J. H., Et Al.

3D Printing biodegradable polyurethane nanocomposite scaffold for heart valve regeneration

3D打印可生物降解的聚氨酯纳米复合材料支架用于心脏瓣膜再生

• 发表时间: 2017
• 作者: Mohmad-Saberi, S

Novel functional vascular stent coating platform via click chemical modification of urethane pre-polymers

通过聚氨酯预聚物的点击化学改性形成新型功能性血管支架涂层平台

• 发表时间: 2016
• 作者: J. Hon Pang, J. Tsui, B. G. Cousins

Biofunctionalization of chemical-cured urethane pre-polymers with endothelial cell selectivity for cardiovascular implants.

用于心血管植入物的具有内皮细胞选择性的化学固化聚氨酯预聚物的生物功能化。

• 发表时间: 2017
• 作者: Pang, J. H

Development of pediatric covered stent using nanocomposite material.

使用纳米复合材料开发儿科覆膜支架。

• 发表时间: 2016
• 作者: Farhatnia, Y., Et Al.