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

该项目将为导管相关血栓形成和感染这两种导管置入术的重要并发症开发一种新颖的预防性解决方案。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命题，将技术从TRL1/2推进到TRL3/4，来实现这一目标。该项目将提供改进通过导管进行的干预措施的手段，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、改善安全性和提高效率使患者和临床医生受益。mof是近年来发展最重要的一类材料。它们是通过连接金属离子或簇与有机连接分子形成延伸网络而形成的纳米多孔固体。其巨大的孔隙度和可接近的表面积（高达5-6,000m2g-1）使其成为储存和运输用途的理想选择。因此，有大量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、氢和甲烷储存、有毒气体捕获）、环境修复、催化、能源应用和药物输送。莫里斯集团率先将其用于医用气体的储存/输送，特别是NO。一氧化氮是一种生物信号分子，具有抗菌、血管扩张、抗血栓和伤口愈合的特性。外源性一氧化氮的输送有可能提供模拟自然过程和解决紧迫的社会挑战的先进疗法。目前，只有使用前药（如三硝酸甘油）或直接吸入气体才能全身递送NO。然而，这些方法可能会导致不必要的副作用。长期以来，临床医生一直在寻求局部和控制NO的递送（例如从植入式装置），但尚未实现。no释放MOFs（由申请人开发）有可能实现这一目标，如果它们可以成功地加工成适当的设备。成功纳入留置导管将减少保健相关感染和血栓形成的风险。正如目前MOF应用研究的许多领域的情况一样，no释放MOF提供的潜在好处的实现取决于其在最终产品特定基质（通常是聚合物）中的性能和加工的成功开发和理解。该项目将通过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复合材料对NO的吸附和释放。它将分析mof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mof在导管和其他形状聚合物基物品中的发展。此外，该项目将采用先进的体外和体内技术来证明其有效性和安全性，并有助于了解和分析导管相关血栓和感染。在此过程中，该项目将扩展对充分利用医疗保健应用mof特性所需材料的基本理解，同时促进将该技术推向工业应用所需的必要设备开发和分析。

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.