Bio-synthetic corneal endothelial grafts for transplantation

角膜移植是最常见的移植类型，每年进行超过180，000例。全球角膜短缺，每70个角膜中只有一个可用，超过1200万人在等待移植。研究人员正在开发方法，以增加仅从一个捐赠者就可以治疗的患者数量。该项目旨在通过将角膜细胞与创新的生物材料相结合来创建生物合成角膜移植物。其主要优点是，一个供体角膜可能会产生30多个移植物。角膜内皮的疾病，例如Fuchs内皮角膜营养不良（FECD）和人工晶状体大泡性角膜病变（PBK），导致显著的视力丧失，并且是角膜移植的最常见原因。角膜内皮层的损伤导致肿胀，从而丧失透明度。用角膜移植替换内皮层可以减少肿胀并恢复透明度。虽然角膜移植在1年时成功率超过80%，但5年后，30%的FECD患者和48%的PBK患者可能因第一次移植失败而需要第二次移植。我们开发了一种基于肽的水凝胶，具有优异的光学和物理特性，可以根据特定的应用进行调整。我们有数据显示，角膜内皮细胞粘附和分裂，在水凝胶表面的数量增加，产生一层细胞，其外观和行为与健康角膜中的细胞非常相似。这种移植物还具有使用角膜外科医生将在患者身上使用的手术工具进行移植操作的物理强度。这种移植物还可以减少角膜肿胀，并在内皮衰竭的兔模型中恢复透明度。这个项目将开发我们的新的生物合成移植沿着翻译途径走向临床。我们的目标是通过改变水凝胶制造方法来实现这一目标，以允许生产更薄的水凝胶，优化培养细胞用于临床使用的方法，并在兔模型中评估这些优化移植物的安全性和有效性。

Corneal transplantation is the most frequent type of transplantation with over 180,000 performed each year. There is a global shortage of corneas with only one available for every 70 required and more than 12 million people on a waiting list for a transplant. Researchers are developing ways to increase the number of patients that can be treated from just one donor. This project aims to do that by combining corneal cells with an innovative biomaterial to create a biosynthetic corneal graft. The major advantage being that one donor cornea could potentially create more than 30 grafts. Diseases of the corneal endothelium, such as Fuchs' endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK), result in significant loss of vision and are the commonest reasons for corneal transplantation. Damage to this endothelial layer of the cornea leads to swelling and thus loss of transparency. Replacement of the endothelial layer with a corneal transplant reduces the swelling and restores transparency. Although corneal transplantation is more than 80% successful at 1 year, after 5 years 30% of people with FECD and 48% of people with PBK may require a second transplant due to failure of their first graft. We have developed a peptide based hydrogel with excellent optical and physical properties that can be tuned depending on the particular application. We have data that show corneal endothelial cells adhere and divide, increasing in number on the surface of the hydrogel to produce a layer of cells that look and behave very similarly to those in a healthy cornea. This graft also has the physical strength to be manipulated for transplantation using surgical tools that a corneal surgeon would use on a patient. This graft also functions to reduce corneal swelling and restores transparency in a rabbit model of endothelial failure. This project will develop our new bio-synthetic graft along the translational pathway towards the clinic. We aim to do this by changing the hydrogel manufacture method to allow production of thinner hydrogels, optimising the method to culture the cells for clinical use and evaluating the safety and efficacy of these optimised grafts in a rabbit model.