The design and manufacture of 3D peptide gels for tissue engineering applications

The cornea is a transparent window located at the front of the eye and has several roles imperative to the main functions of the eye. These include controlling the amount of light reaching the back of the eye, focusing light onto the retina and establishing and maintaining the eye shape. It is composed of three main layers: a stratified epithelium, the stroma, and a single layered endothelium. A damaged cornea can result in blindness, and the most common treatment for this is donor cornea replacement. Some pathologies where a replacement cornea may be required include chemical burns, Steven-Johnson syndrome and autoimmune diseases such as mucus membrane pemphigoid. This procedure is widely used throughout the world, but is not without its limitations. Amongst these are the limited availability of the donor corneas, issues with tissue rejection and infection and finally, the expense of the procedure. An artificial cornea would be able to combat these limitations, as they could be made of a biocompatible synthetic material reducing tissue rejection, they could be manufactured in large volumes and could eliminate expenses such as donor cornea screening.

A recent study at the University of Liverpool developed a poly-E-lysine (pEK) based hydrogel material that was seen to be effective for use in anti-microbial contact lenses. This polymer is based on pEK cross-linked with bis-carboxy fatty acids, the most suitable found to be suberic acid. An optimal monomer composition was established and found to be non-cytotoxic to HCE-T cells and did not inhibit the re-epithelialisation of a cell monolayer. A hydrogel is a water-swollen network of polymer crosslinks, which maintains physical and mechanical properties that make it a desirable material for biomaterial and tissue engineering applications. Their high water content allows them to be introduced into a biological environment without affecting the viability, and also makes them suitable for cell attachment. The mechanical properties of poly-E-lysine specifically can be tailored by altering both the polymer and cross-linking density and the molecular length of the cross linker. For instance, increasing the polymer density directly increases the ultimate tensile strength of the final hydrogel.

The aim of this project is to produce a 3D macro-porous form of this pEK based hydrogel previously tested as a thin film. The design and manufacture of this 3D porous gel will be trialled via a number of routes. These include the controlled 3D printing of porous constructs, the crosslinking of hydrogel fragments and forms of gel casting. This will involve exploring several different printing technologies and determining what is the most suitable for this material. The hydrogel chemistry can further be altered to suit these different technologies and to optimise cell attachment and response. Upon establishing a suitable manufacturing process, the properties of the material could be altered to suit applications within the eye, with the main focus being transparency. Finally, several trials will be performed on the material with this modified architecture to assess its suitability for cell incorporation and attachment. This material could inevitably be used for an artificial cornea, or an in vitro 3D tissue model of the cornea when cells are incorporated.

This project will take place between the Institute of Ageing and Chronic Disease and the School of Engineering and will be supervised by Professor Rachel Williams and Dr Kate Black.