Manufacturing the future: Manufacture of Shaped MOF-Polymer Products for Healthcare Applications

该项目将研究和开发含有多孔材料（称为金属有机框架（MOFs））的挤出聚合物制品的制造和后处理路线。该项目将广泛适用于许多高价值和变革性产品的开发。重点将放在制造多功能医疗设备（特别是导管）的组件上，这些组件将能够增强福祉。该项目旨在确定相关的基本影响因素以及如何控制这些因素，从而制定一套有效生产的指导方针。它还将开发、设计和建立一个原型工艺，首次实现必要的大规模制造后加工。这些双重组件将允许利用MOFs的显着特性来缓解现代社会的一些最紧迫的挑战-医疗保健相关感染，抗菌素耐药性和心脏病。因此，该项目符合21世纪世纪产品研究愿景类别。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，有重要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、氢气和甲烷储存、气体分离、有毒气体捕获）、环境修复和污染防治、催化、能源应用和药物输送。为了充分发挥将MOFs应用于聚合物基产品的创新潜力，必须开发用于它们的掺入和加工的合适方法。许多基于聚合物的制品，包括导管管材，通过挤出制造。然而，迄今为止，文献中缺乏关于使用该技术将MOF加工成成型的基于聚合物的产品组件的研究报道。此外，还没有对这种挤出制品的大规模后处理进行研究，以实现MOF活化和随后的气体加载，这对于任何需要气体吸附/释放的应用来说都是必要的步骤。该项目将解决这种缺乏信息的制造MOF基聚合物制品，并将开发利用MOFs作为输送剂的医学上有用的气体一氧化氮（NO）作为一个模型应用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性能。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。例如，成功地结合到泌尿、心血管和血液透析导管中将减少医疗保健相关的感染，减轻心脏病治疗期间的手术并发症，并降低血液透析期间血栓形成的风险。正如目前在MOF应用研究的许多领域中的情况一样，MOF提供的潜在益处的实现依赖于成功开发和对其加工成最终产品形式的理解。

This project will investigate and develop routes to the manufacture and post-processing of extruded polymer-based articles containing porous materials called metal organic frameworks (MOFs). The project will have widespread applicability to the development of many high value and transformative products. Focus will be placed on the manufacture of components for multifunctional medical devices (particularly catheters) that will enable enhanced well-being. The project seeks to establish the pertinent fundamental contributing factors and how these can be controlled, arriving at a set of guidelines for effective manufacture. It will also develop, design and build a prototype process that achieves, for the first time, necessary post-manufacture processing at scale. These dual components will permit the remarkable properties of MOFs to be harnessed to alleviate some of the most pressing challenges of modern society - healthcare associated infections, antimicrobial resistance and heart disease. As such, this project fits within the 21st Century Products Research Vision category. 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) makes 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, gas separation, toxic gas capture), environmental remediation and pollution prevention, catalysis, energy applications and drug delivery.To realise the full innovative potential of applying MOFs to polymer-based products, suitable methods for their incorporation and processing must be developed. Many polymer-based articles, including catheter tubing, are manufactured by extrusion. To date, however, there is a lack of studies reported in the literature regarding MOF processing into shaped polymer-based product components using this technique. In addition, there are no studies into the large scale post-processing of such extruded articles to enable MOF activation and subsequent gas loading, which are essential steps for any application requiring gas adsorption/release. This project will address this lack of information on the manufacturing of MOF-based polymer articles and will develop the utilisation of MOFs as delivery agents for the medically useful gas nitric oxide (NO) as a model application.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, for example, urinary, cardiovascular and haemodialysis catheters will reduce healthcare associated infections, alleviate procedural complication during the treatment of heart disease, and reduce the risk of thrombosis during haemodialysis. As is currently the case in many areas of MOF application research, realisation of the potential benefits offered by MOFs is reliant on the successful development and understanding of their processing into end-product form.