A dynamic biomaterial-ligand tethering strategy for tissue engineering

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The use of biomaterials to drive the repair, regrowth, or regeneration of damaged biologicaltissue has the potential to revolutionise the treatment of disease. Materials that can presentcells and tissues with powerful biochemical signals, through attached peptides, proteins, andcarbohydrates, are particularly effective at controlling regeneration. However, at present westruggle to grow mature, fully-functioning tissues that can be used in the clinic due to thedifficulty of controlling these signalling events. While nature relies on intricate networks oftightly controlled, dynamic signalling to drive repair, this is in stark contrast to the staticsignals provided by synthetic materials. In this PhD project, we therefore aim to develop newchemistries that allow the reversible attachment of peptide and proteins to biomaterialscaffolds.We will particularly focus on the development of novel conjugation chemistries that allowproteins to be covalently attached to material surfaces via stabilised imines. We will identifyconditions that allow subsequent cleavage of the protein under biocompatible conditions,while regenerating the original reactive groups on the material surface. By doing so, we willenable the attachment of a second signalling protein that can itself be cleaved, allowingiterative cycles of protein presentation. This would represent a major advance in biomaterialschemistry, allowing us to take a major step towards mimicking the complexity of naturaltissues. Key to this goal is the optimisation of the underlying conjugation chemistry, requiringprecise understanding of the reaction equilibria and kinetics which we will study using acombination of photo-physical and materials chemistry techniques. We will then go on toapply our novel chemistries in the design of new biomaterials for cartilage regeneration, bysequentially presenting growth factor signalling proteins that drive tissue development fromcell growth through to tissue maturation.