Bio-synthetic corneal endothelial grafts for transplantation

用于移植的生物合成角膜内皮移植物

• 批准号: MR/W01470X/1
• 负责人: Hannah Levis
• 金额: $ 144.07万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW01470X%2F1
• 关键词: Bio; synthetic; corneal; endothelial; grafts

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.

角膜移植是最常见的移植类型，每年有超过18万例。全球角膜短缺，每70个需要的角膜中只有一个可用，有超过1200万人在等待移植。研究人员正在开发一种方法，以增加一个捐赠者可以治疗的患者数量。该项目旨在通过将角膜细胞与一种创新的生物材料结合起来，创造一种生物合成角膜移植物。主要的优点是一个捐赠角膜可以产生30多个移植角膜。角膜内皮疾病，如Fuchs的内皮性角膜营养不良（FECD）和假性大疱性角膜病变（PBK），会导致严重的视力丧失，是角膜移植最常见的原因。对角膜内皮层的损害会导致肿胀，从而失去透明度。用角膜移植替代内皮层可以减少肿胀并恢复透明。虽然角膜移植在1年内的成功率超过80%，但5年后，30%的FECD患者和48%的PBK患者可能由于第一次移植失败而需要第二次移植。我们已经开发出一种基于肽的水凝胶，具有优异的光学和物理性能，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，水凝胶表面的细胞数量增加，从而产生一层细胞，其外观和行为与健康角膜非常相似。这种移植物还具有物理强度，可以使用角膜外科医生在患者身上使用的手术工具进行移植操作。在兔内皮衰竭模型中，这种移植物还具有减少角膜肿胀和恢复透明度的功能。这个项目将发展我们新的生物合成移植物沿着转化途径走向临床。我们的目标是通过改变水凝胶制造方法来生产更薄的水凝胶，优化临床使用的细胞培养方法，并在兔模型中评估这些优化移植物的安全性和有效性。