About the Project
Background and proof of concept data:
Corneal disease affects millions of people worldwide with higher prevalence in developing countries. Corneal transplantation to replace damaged corneas has been used for decades to treat patients with corneal impairment but replacing corneas alone cannot solve corneal scarring if the patient lacks corneal stem cells. The use of membranes as cell carriers for aiding in corneal disease has been relatively successful, for example, the amniotic membrane (AM) is being used worldwide as a corneal cell carrier. Unfortunately, AM carries a risk of viral transmission which can only be reduced by using costly and not widely available tissue banking protocols.
Our group has been working together with LV Prasad Institute (LVPEI, India) with the aim of delivering new alternatives for simplifying corneal treatments and therefore increasing their accessibility. To date we have been focusing on (i) the use of tissue explants instead of laboratory expanded cells (Simple Limbal Epithelial Transplantation, SLET which is used now successfully in more than 100 centres worldwide) and (ii) the development of a synthetic AM substitute made of PLGA 50:50. The development of this synthetic PLGA membrane has achieved many of its milestones but frustratingly the membrane that has been developed (and tested in an in-man safety study finished July 2018) is stiffer than expected; this occurred as a result of exhaustive solvent removal to reduce solvent concentrations to levels permitted for clinical use (the solvent acts as a plasticiser and when removed the material becomes brittle). Dr. Ortega’s and Dr. Claeyssesn’s laboratories are now working on different approaches to reduce the stiffness of the previously developed corneal electrospun scaffolds via the utilisation of different solvent-systems and the addition of plasticizers. Current data suggests the use of a dual plasticizing system could be a powerful approach to both improve wettability and mechanical performance of the membrane. In essence, we hypothesise that the inclusion of a dual plasticizing system within a polylactide-co-glycolide synthetic electrospun membrane will improve the membrane’s wettability and flexibility, this having a positive effect in cell outgrowth from limbal tissue explants. Therefore, this project aims to manufacture a smart fibrous membrane with tailored stiffness and to assess its performance in vitro and ex vivo using porcine/rabbit limbal tissue explants and a previously optimized wounded cornea model.
The membrane designed in this project could open the door to the development of a new pliable and biocompatible cell carrier to aid patients with corneal impairment.
Candidates must have a first or upper second class honors degree or significant research experience.
How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select 'School of Clinical Dentistry' as the department. Please also state your first and second choice project by entering the project tiles in the 'Research Topic' box on your application.
Interested candidates should in the first instance contact Dr Ortega - firstname.lastname@example.org
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