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疾病的患者。该设备的目标是治疗一系列疾病，其中通常保护性免疫系统攻击身体的组织和器官。这些疾病包括败血症和COVID-19。一个称为细胞因子的分子家族，控制免疫系统在这些疾病中起着关键作用。去除这些分子已被证明可以防止经常导致死亡的组织破坏。脓毒症是ITUs的大部分入院原因，全球医疗保健系统的成本超过800亿英镑。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循环中去除细胞因子。这可以通过将患者的循环暴露于可以吸附这些分子的材料来实现，但是目前设计用于实现的技术是昂贵的，吸收有限，并且众所周知难以制造并且对环境有害。几年前，我们开发了一种新的膜材料，其中包含活化的陶瓷珠，研究表明其具有作为潜在的临床细胞因子吸附剂治疗的真正前景。然而，人们发现不可能安全地大规模生产而不影响环境。通用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生产具有适当结构的新设备的可能性。这些材料可以以与传统聚合物基碳珠相同的方式适当地碳化和活化，而没有相关的制造或环境挑战。这些新材料适用于替代制造工艺，如3D打印。基于我们之前的经验，我们将定义制造条件，以确保我们生产出适当活化的陶瓷结构，这些陶瓷结构可以很容易地结合到过滤装置中，以去除患者血液中的细胞因子。这种设备将是目前方法成本的一小部分，并将导致获得这种宝贵治疗的民主化。在本项目中，我们将设计和验证器械和制造过程，以便将来进行临床部署，制定制造计划、未来临床和临床前试验以及监管批准策略。

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.