Development of a novel, low cost ceramic monolithic extracorporeal adsorption device for the treatment of life-threatening inflammatory diseases

该项目将开发一种新的技术和制造工艺，用于治疗患有危及生命的炎症性疾病的患者。该设备的目标是治疗一系列疾病，在这些疾病中，通常具有保护性的免疫系统攻击身体的组织和器官。这些疾病包括脓毒症和新冠肺炎。控制免疫系统的一系列分子，称为细胞因子，在这些情况下起着关键作用。移除这些分子已被证明可以防止经常导致死亡的组织遭到破坏。脓毒症是TUTS的大部分入院原因，全球医疗保健系统的成本超过800亿GB。减少这些疾病中危险的“细胞因子风暴”的影响的最有希望的方法之一是从患者的血液循环中去除细胞因子。这可以通过将患者的血液循环暴露在可以吸附这些分子的材料中来实现，但目前旨在实现这一目标的技术昂贵，吸收有限，而且制造起来非常困难，而且对环境造成破坏。几年前，我们开发了一种新的膜材料，其中加入了活性陶瓷微珠，研究表明，这种材料真正有希望作为潜在的临床细胞因子吸附剂治疗。然而，人们发现，在不影响环境的情况下，安全地大规模生产是不可能的。多功能3D打印技术的最新发展为该领域开辟了新的途径，并提供了使用与更少的碳排放和环境污染相关的新材料来生产具有适当架构的新设备的可能性。这些材料可以像传统的聚合物碳珠一样进行适当的碳化和活化，而不会带来相关的制造或环境挑战。这些新材料为3D打印等替代制造工艺提供了便利。在我们之前经验的基础上，我们将确定制造条件，以确保我们生产的适当激活的陶瓷结构可以轻松地整合到过滤设备中，以去除患者血液中的细胞因子。这种设备的成本将只是目前方法的一小部分，并将导致获得这种有价值的治疗的民主化。在这个项目中，我们将为未来的临床部署设计和描述设备和制造工艺，为它们的制造、未来的临床和临床前试验以及监管批准战略制定计划。

This project will develop a new technology and manufacturing process for a device aimed at the treatment of patients with life-threatening inflammatory conditions. The device is targeted at the treatment of a family of diseases in which the normally protective immune system attacks the tissues and organs of the body. These diseases include Sepsis and COVID-19\. A family of molecules, called cytokines, which control the immune system play a key role in these conditions. Removing these molecules has been shown to prevent the destruction of the tissues that often results in death. Sepsis is responsible for the majority of admissions to ITUs and has a cost to healthcare system of over £80billion globally. One of the most promising approaches to reducing the impact of the dangerous "cytokine storm" in these diseases is to remove the cytokines from the patient's circulation. This can be achieved by exposing the patient's circulation to materials that can adsorb these molecules, but currently technology designed to achieve are expensive, of limited uptake and are notoriously difficult and environmentally damaging to manufacture. Some years ago we developed a new membrane material which incorporated activated ceramic beads which studies showed to have genuine promise as a potential clinical cytokine adsorbent treatment. However, it was found to be impossible to mass manufacture safely and without environmental impact. The recent development of versatile 3D printing techniques opens up new avenues in this field and presents the possibility to produce new devices with the appropriate architecture using new materials that are associated with less carbon emissions and environmental pollution. These materials can be appropriately carbonised and activated in the same way as conventional polymer-based carbon beads without the associated manufacturing or environmental challenges. These new materials lend themselves to alternative manufacturing processes such as 3D printing. Building on our previous experience, we will define the manufacturing conditions to ensure that we produce appropriately activated ceramic structures that can be easily incorporated into a filter device to remove cytokines from the blood of patients. Such devices will be a fraction of the cost of current approaches and will lead to a democratisation of access to this valuable treatment. In this project, we will design and characterise the device and the manufacturing process with a view to future clinical deployment, producing a plan for their manufacture , future clinical and pre-clinical trials and regulatory approval strategy.