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.

该项目将为导管相关的血栓和感染开发一种新的预防性解决方案，这是导尿术的两个重要并发症。它将通过加速将释放一氧化氮(NO)的金属有机骨架材料研究转化为具有工业意义的命题，将技术从TRL1/2转移到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的手段，并将鼓励开发新的微创治疗方法。它的成果将通过减少并发症、改善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团簇与有机连接分子连接起来形成延伸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 m2g-1)使其成为储存和运输用途的绝对理想之选。因此，有大量的学术活动在开发和研究这些材料，用于各种应用，如气体处理(包括碳捕获、氢和甲烷存储、有毒气体捕获)、环境修复、催化、能源应用和药物输送。Morris集团率先将其用于存储/输送医疗气体，尤其是NO。NO是一种具有抗菌、血管扩张、抗血栓和伤口愈合特性的生物信号分子。外源性传递NO有可能提供模拟自然过程的先进疗法，并应对紧迫的社会挑战。目前，只有使用前体药物(如硝酸甘油)或直接吸入气体才有可能全身释放NO。然而，这些方法可能会导致不想要的副作用。临床医生长期以来一直在寻求局部和受控的NO输送(例如从植入性设备)，但尚未实现。如果能够成功地将NO释放的MOF加工成适当的装置，它们(由申请者开发)就有可能实现这一目标。成功地结合到留置导管中将减少医疗保健相关的感染和血栓的风险。正如目前MOF应用研究的许多领域的情况一样，实现NO释放的MOF提供的潜在好处取决于对其性能的成功开发和对其在终端产品特定基质(通常是聚合物)中的加工的了解。本项目将使用实验和模型来研究聚合物基质、MOF的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在导管和其他成型聚合物制品中的开发。此外，该项目将采用先进的体外和体内技术来证明有效性和安全性，并有助于了解和分析与导管相关的血栓形成和感染。通过这样做，该项目将扩大对材料的基本了解，以充分利用医疗保健应用的MOF的特性，同时促进必要的设备开发和分析，以推动技术走向工业采用。