Nitric Oxide-Releasing Materials to Prevent Catheter Related Thrombosis and Infection

释放一氧化氮的材料可预防导管相关的血栓形成和感染

• 批准号: EP/X014436/1
• 负责人: Russell Morris
• 金额: $ 264.1万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX014436%2F1
• 关键词: Nitric; Oxide; Releasing; Materials; Prevent

This project will develop a novel and preventative solution to catheter-related thrombosis and infection, two important complications of catheterisation. It will achieve this by accelerating the translation of nitric oxide (NO)-releasing metal organic framework material research into an industrially relevant proposition, moving the technology from TRL1/2 to TRL3/4. The project will provide the means to improve interventions conducted via catheterisation and it will encourage development of new, minimally invasive treatments. Its outputs will benefit patients and clinicians by reducing complications, improving safety and increasing efficiency. MOFs are one of the most significant classes of materials to be developed in recent times. They are nanoporous solids formed by connecting metal ions or clusters with organic linking molecules to form extended networks. Their huge porosity and accessible surface area (up to 5-6,000m2g-1) make them absolutely ideal for storage and delivery uses. As a result, there is significant academic activity developing and studying these materials for a diverse range of applications such as gas handling (including carbon capture, hydrogen and methane storage, toxic gas capture), environmental remediation, catalysis, energy applications and drug delivery. The Morris group has pioneered their use for the storage/delivery of medical gases, particularly NO.NO is a biological signalling molecule that has antimicrobial, vasodilatory, antithrombotic and wound healing properties. Exogenous delivery of NO has the potential to offer advanced therapies that mimic natural processes and address pressing societal challenges. Currently, only systemic NO delivery is possible using pro-drugs (e.g. glyceryl trinitrate) or, direct inhalation of the gas. However, these approaches can lead to unwanted side-effects. Localised and controlled delivery of NO (e.g. from implantable devices) has long been sought by clinicians but is yet to be realised. NO-releasing MOFs (developed by the applicants) have the potential to achieve this goal if they can be processed successfully into the appropriate devices. Successful incorporation into indwelling catheters will reduce healthcare associated infections and the risk of thrombosis.As is currently the case in many areas of MOF application research, realisation of the potential benefits offered by NO-releasing MOFs is reliant on the successful development and understanding of their performance and processing in end-product-specific matrices (typically polymers). This project will use experimentation and modelling to investigate how polymer matrices, MOF loading and distribution influence NO adsorption and release by polymer-MOF composites. It will analyse the stability of MOFs towards sterilisation techniques, and it will develop advanced manufacturing aspects that will benefit the development of MOFs in catheters and other shaped polymer-based articles. Further, the project will deploy advanced in vitro and in vivo techniques to demonstrate efficacy and safety, and to contribute to the understanding and analysis of catheter-related thrombosis and infection. In doing so, this project will expand the fundamental understanding of the materials necessary to fully harness the properties of MOFs for healthcare application, whilst simultaneously facilitating the necessary device development and analysis required to move the technology towards industrial adoption.

该项目将开发出一种新颖的预防解决方案，以解决导管相关的血栓形成和感染，这是导管插入的两种重要并发症。它将通过将一氧化氮（NO）的金属有机框架材料研究转化为具有工业相关的命题，将技术从TRL1/2转移到TRL3/4。该项目将提供改善通过导管进行干预措施的方法，并鼓励开发新的，微创的治疗方法。它的产量将通过减少并发症，提高安全性和提高效率来使患者和临床医生受益。 MOF是最近要开发的最重要的材料类别之一。它们是通过将金属离子或簇与有机链接分子连接到形成扩展网络的纳米固体。它们巨大的孔隙率和可访问的表面积（高达5-6,000m2g-1）使它们绝对是存储和交付用途的理想选择。结果，为各种应用（包括碳捕获，氢和甲烷储存，有毒气体捕获），环境修复，催化，能量应用和药物输送等多种应用，正在开发和研究这些材料。莫里斯集团（Morris Group）开创了其用于储存/递送医用气体的使用，尤其是No.NO是一种生物信号分子，具有抗菌，血管舒张，抗血栓形成和伤口愈合的特性。 NO的外在交付有可能提供模仿自然过程并应对紧迫社会挑战的先进疗法。当前，只有使用促毒物（例如糖酸酯）或直接吸入气体的系统性输送。但是，这些方法可能导致不必要的副作用。长期以来一直在寻求NO的本地化和受控的NO（例如，从可植入设备中），但尚未实现。如果可以成功地将其处理到适当的设备中，则不释放MOF（由申请人开发）有可能实现此目标。成功地纳入留置导管将减少与医疗保健相关的感染和血栓形成的风险。目前在MOF应用研究的许多领域都是如此，实现了不释放MOF所提供的潜在收益，这依赖于成功的发展和理解其对最终产物特异性基质的性能和处理的理解。该项目将使用实验和建模来研究聚合物矩阵，MOF负载和分布如何影响聚合物-MOF复合材料的吸附和释放。它将分析MOF对灭菌技术的稳定性，并将开发出先进的制造方面，从而使MOF在导管和其他基于聚合物的基于聚合物的文章中有益。此外，该项目将在体外和体内技术中部署先进的体外技术，以证明功效和安全性，并有助于理解和分析与导管相关的血栓形成和感染。在此过程中，该项目将扩大对完全利用MOF在医疗保健应用的特性所必需的材料的基本理解，同时促进将技术推向工业采用所需的必要设备开发和分析。