PhD Research Project: Building Extracellular Matrix in the Laboratory

Research within the multidisciplinary Biomaterials and Bioengineering group has several broad aims including the development of novel tissue engineering scaffolds and novel methods to synthesise the scaffolds, the translation of these developments to the clinic and new ways to characterise and image the behaviour of these scaffolds.

Tissue-engineered scaffolds are beginning to be used in the clinic to repair tissue defects. Generally, synthetic scaffolds are used either in an acellular form, with the expectation that the patient’s own cells will invade after implantation, or seeded with cells prior to implantation. However both strategies have potential problems; acellular scaffolds may not be fully functional until sufficient cells have invaded the entire scaffold; while when seeding cells first these can be either donor cells, requiring donor recipient immune-compatibility, or the patient’s own cells, which can result in increased lead times to prepare the tissue engineered scaffold.

Recent studies have demonstrated the potential benefits of seeding synthetic scaffolds with cells in the laboratory, allowing the cells to produce an extracellular matrix (ECM) and then de-cellularizing the scaffold to remove the cellular components while leaving the ECM behind. This ECM scaffold can then be implanted and would be hypothesized to have better mechanical and functional characteristics than a purely synthetic scaffold without the problems of incompatibility or long lead times arising following the inclusion of cells. However little is known about the impact of scaffold structure and material, culture conditions or cell seeding protocol on the nature of the ECM formed in this way.

The aim of this project would be to to grow cells on a range of synthetic scaffolds, remove the cells and evaluate the ECM formed. To this end we will use a combination of cell culture, scaffold synthesis and characterisation, non-invasive Second Harmonic Generation and two-photon excitation fluorescence imaging to non-destructively evaluate the ECM formed, and immunolabeling techniques. This project will enable us to develop our understanding of the impact of variations in scaffold structure upon collagen/elastin formation and the resulting mechanical properties in the decellularized scaffold.

Funding Notes

Candidates should be self-funded, sponsored, or applying for Scholarships. The deadline for Faculty/University Scholarships is February each year - for more information see: www.shef.ac.uk/postgraduate/research/scholarships

Candidates should have or expect to gain a good Honours degree with 2i or above in Materials Science and Engineering or related discipline.

The University of Sheffield English Language requirements are described at https://www.sheffield.ac.uk/postgraduate/info/englang; in general, you will either need an IELTS grade of 6.5 with a minimum of 6.0 in each component, or a degree or postgraduate diploma awarded by an institution in a majority English-speaking country.