Bio-synthetic corneal endothelial grafts for transplantation
Lead Research Organisation:
University of Liverpool
Department Name: Eye and Vision Science
Abstract
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.
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.
Technical Summary
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 leads to oedema and thus loss of transparency. Replacement of the endothelial layer with a corneal transplant reduces the oedema and restores transparency. Although corneal transplantation is more than 80% successful at 1 year, five-year graft survival rates are significantly reduced to 70% for FECD and 52% for PBK, meaning that patients often require a second transplant. There is a global shortage of corneas with only one available for every 70 required, therefore, there is an opportunity to combine biomaterials with in vitro expanded corneal endothelial cells (CECs) to produce multiple bioengineered grafts from each donor cornea. These biomaterials not only serve as a carrier for CEC transplantation but may also enhance cell function to increase the long-term success of transplanted grafts.
We have developed a poly-epsilon-lysine based hydrogel with excellent optical and mechanical properties that can be controlled by the nature and percentage of the cross-links and the density of the peptide. We have data that show primary CECs adhere and proliferate on the surface of the gel to produce a confluent monolayer and that this graft has the physical integrity to be manipulated for transplantation using a clinical delivery device. Furthermore, the graft functions to restore corneal thickness and transparency in an in vivo rabbit model of endothelial failure.
This study will develop our technology along the translational pathway by improving the crosslinking method to reproducibly allow production of thinner hydrogels, optimising the manufacture to allow scale up and culture of human CECs in a GMP aligned protocol and evaluating the safety and efficacy of these optimised grafts in an in vivo rabbit model.
We have developed a poly-epsilon-lysine based hydrogel with excellent optical and mechanical properties that can be controlled by the nature and percentage of the cross-links and the density of the peptide. We have data that show primary CECs adhere and proliferate on the surface of the gel to produce a confluent monolayer and that this graft has the physical integrity to be manipulated for transplantation using a clinical delivery device. Furthermore, the graft functions to restore corneal thickness and transparency in an in vivo rabbit model of endothelial failure.
This study will develop our technology along the translational pathway by improving the crosslinking method to reproducibly allow production of thinner hydrogels, optimising the manufacture to allow scale up and culture of human CECs in a GMP aligned protocol and evaluating the safety and efficacy of these optimised grafts in an in vivo rabbit model.
