Establishing Process Control for the Manufacturing of Corneal Tissues in Clinical Applications

全世界每年约有150万例角膜盲症确诊病例和1000万未经治疗的患者。目前，世界范围内捐献的角膜组织短缺，需要替代的工程解决方案。还迫切需要验证所有捐赠组织的状况，以便认为其可用于移植。一旦确定了初始状态，就可以检查包括运输、储存和使用准备在内的后续过程，以确定是否在任何阶段对组织造成损伤。我们需要建立稳健的措施，因为目前的方案缺乏必要的生产控制，以创建适合常规临床应用的可重现生产工艺。这就需要开发新的定量表征工具，主要用于测量输入材料的质量，最终目标是开发测量和量化下游加工技术的能力。这将允许确定定义的组织规格，以及能够审核供体组织以确定其移植适用性的系统。为了确定设计规范，将与莱斯特皇家医院联合对健康与非健康角膜组织进行审核。这种能力使组织工程过程能够得到检查，包括去细胞化，这有可能回收被认为不适合作为部分厚度移植物移植的角膜组织。激光散斑干涉仪的使用最近已被证明提供了一种机械测量角膜特性和定义角膜组织适合性的近瞬时手段。该项目旨在扩展这项工作，建立过程控制，并检查诊断圆锥角膜等早期角膜问题的潜力。

There are approximately 1.5 million cases of corneal blindness diagnosed annually and 10 million untreated patients worldwide. Presently, worldwide shortages of donated corneal tissues warrant the need for alternative engineered solutions. There is also an immediate demand to verify the condition of all donated tissues such that it can be deemed viable for transplantation. Once the initial state has been determined, subsequent processes including transportation, storage and preparations for use, can be examined to determine if at any stage damage is inflicted upon the tissue. We need to establish robust measures since current protocols lack manufacturing controls necessary to create a reproducible manufacturing process suitable for regular clinical application. This requires the development of novel quantitative characterisation tools to measure primarily the quality of input materials, with the ultimate aim to develop a capability to measure and quantify downstream processing techniques. This will allow for the determination of defined tissue specifications, and a system capable of auditing donor tissue to determine its suitability for transplantation. In order to determine design specifications, an audit of healthy versus non-healthy corneal tissues will be performed in conjunction with Leicester Royal infirmary Hospital.Such a capability enables tissue-engineering processes to be examined including decellurisation, which has the potential for recycling corneal tissues deemed unsuitable for transplantation as partial thickness grafts. The use of laser speckle interferometric instruments has recently been shown to provide a near instantaneous means of mechanically measuring corneal properties and defining the suitability of corneal tissue. This project seeks to extend this work, establish process controls and examine the potential for diagnosing early onset corneal issues such as keratoconus.