The use of biomaterials to regrow or repair damaged biological tissue has the potential to revolutionise how we treat disease. These materials must be able to provide both a 3D ‘scaffold’ to support cell growth, and the instructions needed to direct tissue development. In this project, we will develop new dynamic chemical networks that provide biomaterials with tunable self-healing properties that can be tailored for a specific patient.
Dynamic materials that can respond to stimuli, repair themselves when damaged, and be remodelled by growing cells are particularly attractive, but current material designs rely on specific chemistries that provide the scaffolds with a limited set of mechanical properties that cannot be varied. Materials are therefore often poorly matched to different target diseases or tissues. By creating tunable materials during this project, we will provide a powerful platform for the design of ‘personalised’ biomaterials for treating disease.
i) Design dynamic covalent chemistries able to respond to applied stimuli; ii) Synthesise self-healing polymer networks and hydrogel scaffolds; iii) Investigate ability of biomaterials to drive stem cell growth and differentiation;
This highly interdisciplinary project will combine elements of organic synthesis, polymer chemistry, materials science, and cell biology.
We will first synthesise small molecule model systems using aromatic, carbonyl, and peptide chemistries, to design covalent linkages that are dynamic over several timescales. We will use a combination of NMR and fluorescence studies to quantify reaction rates, equilibria, and stabilities, and inform the optimisation of these chemistries.
We will then go on to synthesise polymers containing these small molecules using living radical polymerisation techniques such as RAFT. Polymers of different lengths and compositions will be characterised and screened for their ability to form hydrogels. The capacity of these gels to self-heal will be monitored by rheology and fluorescence.
Finally, we will use these hydrogels as substrates for the growth of human mesenchymal stem cells (hMSCs). We will study how gels with different properties are able to influence the behaviour of these cells by studying their gene expression profiles and the chemical characteristics of the matrix they deposit.
Self-healing, dynamic scaffolds are at the cutting-edge of biomaterials design and have been shown to have a powerful effect on growing tissues. However, the rates of healing and responsiveness are typically fixed for a given chemistry. Here, we will develop biomaterials that possess precisely tunable healing rates for the first time. To do this, we will exploit novel chemistry for the production of dynamic, aromatic carbonyls, in which the choice of substituents and linkers has a significant effect on stability. We will exploit a fluorescence based platform, recently developed in the Spicer Group, to screen these dynamic bonds under a wide range of conditions, allowing us to identify chemistries that are best suited to a particular biological tissue.
Training: The highly interdisciplinary nature of this project will provide applicants with a broad range of skills across applied and translational chemistry, placing them in an ideal position for a future career in the biomedical sciences. The student will join the Molecular Materials Group at York which brings together expertise in the chemical design of materials for next-generation technologies. The student will receive specific training in advanced organic synthesis, peptide and biomaterial chemistry, and rheology from the Spicer and Smith Groups, and mammalian cell culture training from their collaborators in the Department of Biology.
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.