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

该项目将开发一种新的预防性解决方案，以解决导管相关血栓形成和感染，这是导管插入术的两个重要并发症。它将通过加速将释放一氧化氮（NO）的金属有机框架材料研究转化为工业相关的主张来实现这一目标，将该技术从TRL 1/2转移到TRL 3/4。该项目将提供改善通过导管进行干预的手段，并将鼓励开发新的微创治疗方法。其产出将通过减少并发症、提高安全性和提高效率而使患者和临床医生受益。MOF是近年来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连接分子连接以形成扩展网络而形成的纳米多孔固体。其巨大的孔隙率和可接近的表面积（高达5-6，000 m2 g-1）使其绝对适合存储和交付用途。因此，有显着的学术活动开发和研究这些材料的各种应用，如气体处理（包括碳捕获，氢气和甲烷存储，有毒气体捕获），环境修复，催化，能源应用和药物输送。Morris集团率先将其用于医疗气体的储存/输送，特别是NO。NO是一种生物信号分子，具有抗菌，血管扩张，抗血栓形成和伤口愈合特性。NO的外源性递送具有提供模拟自然过程并解决紧迫的社会挑战的先进疗法的潜力。目前，只有全身NO输送是可能的，使用前药（如甘油三硝酸酯）或直接吸入气体。然而，这些方法可能导致不希望的副作用。临床医生长期以来一直在寻求NO的局部和受控递送（例如来自可植入装置），但尚未实现。释放NO的M0 F（由申请人开发）如果能够被成功地加工到适当的装置中，则具有实现该目标的潜力。成功地加入留置导管将减少医疗相关的感染和血栓形成的风险。正如目前在许多领域的MOF应用研究的情况下，实现NO释放MOFs提供的潜在好处依赖于成功开发和理解其性能和在最终产品特定基质（通常是聚合物）中的加工。该项目将使用实验和建模来研究聚合物基质，MOF负载和分布如何影响聚合物-MOF复合材料的NO吸附和释放。它将分析MOFs对灭菌技术的稳定性，并将开发先进的制造方面，这将有利于导管和其他成型聚合物制品中MOFs的开发。此外，该项目将部署先进的体外和体内技术，以证明有效性和安全性，并有助于了解和分析导管相关血栓形成和感染。在此过程中，该项目将扩大对充分利用MOF特性用于医疗保健应用所需材料的基本理解，同时促进必要的设备开发和分析，以将该技术推向工业应用。

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.