DEVELOPMENT OF ELECTROSPUN SCAFFOLDSFOR TISSUE
ENGINEERING/BIOENGINEERING OF THE HUMAN CORNEA
Supervisors: Professor Sheila MacNeil (Engineering Materials)
and Dr Steve Rimmer (Chemistry)
University of Sheffield
There are a number of inherent immune disorders, diseases and trauma which can
cause blindness because of corneal dysfunction. It has been estimated that 45
million people worldwide are bilaterally blind and another 135 million have severely
impaired vision because of loss of corneal transparency. Corneal opacity can result
from a dysfunction of one of the three cell types in the cornea, the epithelium,
keratocytes or endothelium. If a patient loses the limbal epithelial stem cell barrier to
the cornea then the cells which take the places of these are conjunctival cells which
quickly form a cloudy, often scarred, tough membrane over the eye which is
extremely painful and causes reduced vision, if not loss of vision. The frontline
treatment remains corneal transplantation using cadaveric corneas from tissue
banks. However, this is not always possible and there may be practical and cultural
reasons why donor corneas are not used. Also patients who have lost all surviving
autologous limbal epithelial stem cells (LEC) from limbal stem cell niches or
protected pockets within the limbus of the eye cannot be treated with cadaveric
corneas. Fortunately one can use cells from the contralateral unaffected eye if
available or donor corneal cells (with immunosuppression) or oral mucosa cells.
There are several major tissue engineering and bioengineering challenges to be
addressed - how to best deliver cultured cells to the eye , how to ensure long term
survival of the cultured cells and how to replace the damaged cornea with a
biosynthetic corneal inlay which supports the attachment, proliferation and migration
of cultured cells.
Professor MacNeil and Dr Rimmer have made significant progress in developing a
hydrogel inlay to be used in the treatment of diseases of the cornea. This hydrogel
was functionalised with carbon chains of varying length and demonstrated to be able
to support the re-epithelialisation of the hydrogel when corneal epithelial cells were
co-cultured with corneal stromal cells (Rimmer et al, Biomaterials, 2007). One of the
remaining challenges of this work however is to develop an outer ring (or skirt) of
material which can be placed within the eye and will become repopulated with the
stromal cells of the eye. The MacNeil laboratory also has experience of developing
both electrospun scaffolds for soft tissue engineering (Blackwood et al, 2008), these
can deliver an antinflammatories such as Ibuprofen and Aspirin (Patent applied for) (
Canton et al In Press) and also of engineering surfaces for the culture and transfer of
corneal cells from a coated contact lens to a denuded cornea (using an ex vivo
animal model) (Deshpande et al, Tissue Engineering, In Press).
The aim of this project will be to combine our expertise in developing biodegradable
electrospun carriers and biofunctional polymers to produce a material that can
integrate into the cornea for treatment of patients with corneal diseases. The work
will involve the use of electrospun blends based on degradable polymers containing
functional polymer additives. Oral mucosa cells as well as corneal epithelial cells will
be examined for their ability to survive and form a new cornea on these materials.
This project will provide extensive training in biomaterials production (electrospun
scaffolds capable of delivering anti-inflammatories, hydrogel production and
modification of hydrogels with amines) and tissue engineering. The PhD student will
be involved in designing the bioengineering approaches, fabricating materials and
evaluating them in in vitro experimentation.
Rimmer S, Wyman P, Johnson C, Zhao B, Fullwood NJ and MacNeil S (2007)
Epithelialization of hydrogels achieved by amine functionalization and co-culture with
stromal cells. Biomaterials 28(35), 5319-5331
Blackwood K, McKean R, Canton I, Freeman C, Franklin K, Cole D, Brook I, Farthing
P, Rimmer S, Haycock JW, Ryan AJ, MacNeil. (2008)
Development of
biodegradable electrospun scaffolds for dermal replacement. Biomaterials
29(21):3091-104
Deshpande P, Notara M, Bullett N, Daniels J, Haddow D, MacNeil S. (2009).
Development of a surface modified contact lens for the transfer of cultured limbal
epithelial cells to the cornea for ocular surface diseases. Tissue Engineering (In
Press)
Canton I, McKean R, Charnley M, Blackwood K, Fiorica C, Ryan AJ, MacNeil S.
(2009) Development of an Ibuprofen releasing biodegradable PLA/PGA electrospun
scaffold for wound repair. Biotechnology and Bioengineering (In press)