Bioactive-loaded scaffolds for conjunctiva regeneration

Description

Are you passionate about tissue engineering and regenerative medicine? Join us in undertaking a highly innovative PhD project focused on the conjunctiva, an under-researched yet incredibly vital tissue essential for eye protection and ocular surface homeostasis.

Multiple diseases can impair conjunctival function, often requiring surgical intervention. Our novel approach aims to revolutionise treatment through the development of a biomaterial substrate that supports a stratified epithelium with embedded, mucin-secreting goblet cells.

In our previous studies, we demonstrated electrospun fibres loaded with decellularised tissue matrix significantly enhances the stratification of human conjunctival epithelial cells compared to synthetic fibres alone. These promising matrix-containing scaffolds have the potential to become advanced therapy medicinal products for conjunctival repair and regeneration.

This PhD project offers a unique opportunity to explore the impact of incorporating bioactives, such as powdered decellularised tissue matrix or extracellular vesicles (EVs), sourced from conjunctival tissue and cells into synthetic polymers. You will create bioactive fibre scaffolds and investigate their influence on conjunctival epithelial and goblet cell responses.

This cross-disciplinary and highly original study not only aims to advance scientific knowledge but also holds the potential to transform clinical approaches to conjunctival diseases. If you're ready to contribute to cutting-edge research and make an impact in the field of biomaterials and tissue engineering, we encourage you to apply!

Studentship hypothesis and aims

Hypothesis: Incorporating bioactives into 3D biomimetic scaffolds will promote ex vivo conjunctival cell expansion and facilitate the development of conjunctival tissue engineered in vitro.

This hypothesis will be tested via the following aims:

-           To decellularise animal and human conjunctiva (and dermal) tissues and produce extracellular matrix powders

-          To cultivate conjunctival EVs from in vitro culture

-          To produce bioactive-loaded fibre scaffolds using electrospinning and melt electrowriting techniques and characterise their material properties (e.g. handleability, strength and hydrophilicity)

-          To evaluate in vitro response of human conjunctiva progenitor and cell lines within bioactive-loaded scaffolds in terms of conjunctival cell phenotype expression (e.g. epithelial cell stratification and mucin-secreting goblet cells)

Methods and training

You will undertake a variety of experiments and learn a range of new skills, including fibre production and development (electrospinning, melt electrowriting), material characterisation (mechanical properties, scaffold topography, imaging-mass spectrometry, hydrophilicity), animal and human eye tissue dissection, tissue decellularisation, cultivation and isolation and characterisation of EVs, primary and immortal cell culture, in vitro assays (viability, growth, phenotype).

You will be supervised by a collaborative team from the Institute of Life Course and Medical Sciences, including Drs Lucy Bosworth and Kevin Hamill (Department of Eye and Vision Science) and Prof. Mandy Peffers (Department of Musculoskeletal Ageing Science). The supervisory team has wide-ranging expertise and will provide training and support in all relevant laboratory and analytical techniques.

The Institute of Life Course and Medical Science is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a silver Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Applications should be made to project supervisors in the first instance via CV and cover letter. This is for all applications. Only when a candidate has been selected following interview will a formal online application be made.

Availability

Open to UK applicants

Funding information

Funded studentship

3-year funding provided by the Crossley-Barnes bequest to support a UK home student.

Supervisors

References

Bosworth, L.A., Doherty, K.G., Hsuan, J.D., Cray, S.P., D’Sa, R.A., Pineda Molina, C., Badylak, S.F. and Williams, R.L., 2021. Material characterisation and stratification of conjunctival epithelial cells on electrospun poly (ε-caprolactone) fibres loaded with decellularised tissue matrices. Pharmaceutics, 13(3), p.318.
Ramos, T., 2018. An in vitro investigation of human ocular surface epithelial stem cell homeostasis (Doctoral dissertation, University of Liverpool).
Makuloluwa, A.K., Hamill, K.J., Rauz, S., Bosworth, L., Haneef, A., Romano, V., Williams, R.L., Dartt, D.A. and Kaye, S.B., 2023. The conjunctival extracellular matrix, related disorders and development of substrates for conjunctival restoration. The Ocular Surface, 28, pp.322-335.
Makuloluwa, A.K., Hamill, K.J., Rauz, S., Bosworth, L., Haneef, A., Romano, V., Williams, R.L., Dartt, D.A. and Kaye, S.B., 2021. Biological tissues and components, and synthetic substrates for conjunctival cell transplantation. The Ocular Surface, 22, pp.15-26.