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

全世界每年约有150万名确诊的角膜失明患者和1000万名未经治疗的患者。目前，世界范围内捐赠的角膜组织短缺，需要替代的工程化解决方案。还有一种迫在眉睫的需求是核实所有捐赠组织的状况，以便可以认为它可以进行移植。一旦确定了初始状态，就可以检查包括运输、储存和准备使用在内的后续过程，以确定在任何阶段是否对组织造成损害。我们需要建立强有力的措施，因为目前的方案缺乏必要的制造控制，以创建适合常规临床应用的可重复制造工艺。这就要求开发新的量化表征工具，以主要衡量投入材料的质量，最终目的是发展衡量和量化下游加工技术的能力。这将允许确定已定义的组织规格，以及能够审计供体组织以确定其是否适合移植的系统。为了确定设计规格，将与莱斯特皇家医院一起对健康和不健康的角膜组织进行审计。这种能力使组织工程过程得以检查，包括脱细胞，这可能会回收被认为不适合作为部分厚度移植物移植的角膜组织。激光散斑干涉仪器的使用最近被证明提供了一种几乎瞬时的方法来机械地测量角膜属性并确定角膜组织的适合性。该项目旨在扩展这项工作，建立过程控制，并检查诊断早期发病的角膜问题，如圆锥角膜的可能性。

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.