Background. Growth of tissue from stem cells is a frontier technology in regenerative medicine. Integral to any such work is the development of effective materials on/in which stem cells can be cultured and allowed to differentiate into target cells. Hydrogels are ideally suited for tissue growth as they are highly solvated, biocompatible soft materials with tunable mechanical properties. Much use has been made of polymer gels in this regard. Less exploited, however, are gels self-assembled from low-molecular-weight building blocks. Such gels have particular potential because of their high tunability, allowing the incorporation of different functionalities to direct the tissue. They are also reversible materials and can potentially be easily disassembled and removed once cell growth is complete.
Objectives. Recently, there has been interested in shaping and structuring self-assembled gels (Nat. Rev. Mat. 2019, 4, 463). This work, much of it led by the Smith Group in York, has potential for application for tissue engineering. If cells can be cultured in shaped or patterned gels, this offers the potential to allow the cells to grow and differentiate with shapes and patterns directed by the material – programmed by the chemist. This proposal builds on recent developments in the Smith group to generate shaped/patterned gels, in particular with constrained and controlled shapes, and then culture stem cells within them. The goal is to understand how programming the chemistry impacts on the resulting biology. The long terms objective of this research would be to use these shaped gels to generate well-defined ‘organoids’ of desired tissue type and shape, suitable for use as animal model replacements in clinical studies of (e.g.) drug activity.
Experimental Approach. The student will generate multi-component gels based on mixtures of low-molecular-weight gelators and polymers. This will involve organic and materials synthesis, gel fabrication and detailed analytical techniques. Spatial resolution and patterning of these materials will be achieved by controlled diffusion and/or photopatterning. The student will then, in collaboration with researchers in Prof Paul Genever’s lab (Department of Biology) explore the potential for stem cell growth and the ability to remove the gel at the end of the cell growth process to leave self-standing ’organoid’ tissue. This project therefore takes a multidisciplinary approach to exploring the interface between chemistry and biology and the ways in which materials can exert their preferences on stem cells.
Novelty. As noted above, the shaping and structuring of self-assembled gels is a new area of research, and the use of self-assembled gels for tissue engineering is also only just beginning to emerge. Combining the two, and using shaped and patterned gels of this type of tissue culture is therefore at the frontier of the field. The project aligns with, and extends, EPSRC-funded research currently ongoing within the Smith Group (EP/P03361X/1).
Training. Outstanding interdisciplinary training will be provided in chemical synthesis, materials fabrication and analysis and biological cell culture. This offers a unique opportunity to the PhD student. The field of Biomaterials is a thriving international area of research, and the student will be well-placed to go on to jobs in industry or academia, like previous PhD students from the Smith Group. The student will be part of the wider Molecular Materials Group, which includes other groups interested in self-assembled materials and/or tissue engineering. Joint group meetings will provide exposure to a wide range of different research. The student will be encouraged to attend national and international conferences. Students in the Smith group have an excellent track record of attending, and winning awards, at such events. Smith group PhD students also contribute to departmental teaching in a high-quality way.
All Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills: https://www.york.ac.uk/chemistry/postgraduate/idtc/
The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/
. This PhD project is available to study full-time or part-time (50%).
This PhD will formally start on 1 October 2020. Induction activities will start on 28 September.