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Design and fabrication of a smart biomaterial device with artificial niches for aiding corneal healing


   School of Clinical Dentistry

  Dr I Ortega  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Corneal disease affects millions of people worldwide with higher prevalence in developing countries. Corneal transplantation and the use of membranes as cell carriers (amniotic membrane, AM) have been relatively successful. Unfortunately, AM is costly and its availability is limited.

Researchers at Sheffield have 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. One of our approaches has been the development of a synthetic AM substitute that includes microfeatures to mimic the limbal niches of the cornea. Limbal stem cells are believed to reside in the limbus in well-define microenvironments or niches; these niches provide physical support to the limbal stem cells. Our first prototype niche-containing materials were regarded by our clinical collaborators at LVPEI as potentially very useful to assist them at the time of surgery. These niche structures could be use as guiding points and as points for securing tissue explants to the delivery membranes avoiding the use of fibrin glue (fibrin is expensive and not available in many countries and requires considerable expertise in its use).

Therefore, in this project we aim to design and manufacture a new microfabricated corneal membrane with improved partially enclosed niche designs, able to retain the corneal tissue explants delivered during SLET surgery (Simple Limbal Epithelial Transplantation). The project also will aim to understand the biological contribution of incorporating such niche structures to the membranes using an ex vivo corneal model previously developed and optimised at Sheffield.

In essence, the project combines the use of advance manufacturing techniques with biological testing for delivering a membrane to aid in corneal healing. It is a clear example of a multidisciplinary projectwhich ultimately aims to develop a biomedical device. The research goes beyond what the team has previously explored, providing a new approach which takes on surgeon’s feedback and proposes the fabrication of a partially-enclosed and self-holding microfeature that can be incorporated into a membrane. In addition to the involvement of advanced manufacturing challenges, the project seeks to generate new biological understanding via exploring differentiation and migration pathways resulting from the inclusion of limbal tissue explants within the proposed microstructures.

The student undertaking this research will work in a fruitful, supportive and multidisciplinary environment in the Mechanisms of health & disease research group at Sheffield.

To start in either October 2022 or March 2023.


Funding Notes

Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience in the areas of Biomedicine, Bioengineering, Biology, Chemistry or Materials Science.
Enquiries:
Interested candidates should in the first instance contact Dr. Ilida Ortega Asencio ()
How to apply:
Please complete a University Postgraduate Research Application form available here: View Website
Please clearly state the prospective main supervisor in the respective box and select 'Clinical Dentistry' as the department.

References

(1). Ramachandran, C., et al., Synthetic biodegradable alternatives to the use of the amniotic membrane for corneal regeneration: assessment of local and systemic toxicity in rabbits. British Journal of Ophthalmology, 2019. 103(2): p. 286-292;
(2). Paterson, T.E., et al., Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 2017. 231(6): p. 565-574;
(3). Ortega, I., et al., Fabrication of biodegradable synthetic perfusable vascular networks via a combination of electrospinning and robocasting. Biomaterials Science, 2015. 3(4): p. 592-596;
(4). Ortega, I., et al., Characterisation and evaluation of the impact of microfabricated pockets on the performance of limbal epithelial stem cells in biodegradable PLGA membranes for corneal regeneration. Biomaterials Science, 2014. 2(5): p. 723-734; (5). Ortega, I. et al., Combination of Microstereolithography and Electrospinning to Produce Membranes Equipped with Niches for Corneal Regeneration. Acta Biomaterialia, 2014. (91): p. e51826.

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