A dynamic biomaterial-ligand tethering strategy for tissue engineering
Lead Research Organisation:
University of York
Department Name: Chemistry
Abstract
The use of biomaterials to drive the repair, regrowth, or regeneration of damaged biological
tissue has the potential to revolutionise the treatment of disease. Materials that can present
cells and tissues with powerful biochemical signals, through attached peptides, proteins, and
carbohydrates, are particularly effective at controlling regeneration. However, at present we
struggle to grow mature, fully-functioning tissues that can be used in the clinic due to the
difficulty of controlling these signalling events. While nature relies on intricate networks of
tightly controlled, dynamic signalling to drive repair, this is in stark contrast to the static
signals provided by synthetic materials. In this PhD project, we therefore aim to develop new
chemistries that allow the reversible attachment of peptide and proteins to biomaterial
scaffolds.
We will particularly focus on the development of novel conjugation chemistries that allow
proteins to be covalently attached to material surfaces via stabilised imines. We will identify
conditions that allow subsequent cleavage of the protein under biocompatible conditions,
while regenerating the original reactive groups on the material surface. By doing so, we will
enable the attachment of a second signalling protein that can itself be cleaved, allowing
iterative cycles of protein presentation. This would represent a major advance in biomaterials
chemistry, allowing us to take a major step towards mimicking the complexity of natural
tissues. Key to this goal is the optimisation of the underlying conjugation chemistry, requiring
precise understanding of the reaction equilibria and kinetics which we will study using a
combination of photo-physical and materials chemistry techniques. We will then go on to
apply our novel chemistries in the design of new biomaterials for cartilage regeneration, by
sequentially presenting growth factor signalling proteins that drive tissue development from
cell growth through to tissue maturation.
tissue has the potential to revolutionise the treatment of disease. Materials that can present
cells and tissues with powerful biochemical signals, through attached peptides, proteins, and
carbohydrates, are particularly effective at controlling regeneration. However, at present we
struggle to grow mature, fully-functioning tissues that can be used in the clinic due to the
difficulty of controlling these signalling events. While nature relies on intricate networks of
tightly controlled, dynamic signalling to drive repair, this is in stark contrast to the static
signals provided by synthetic materials. In this PhD project, we therefore aim to develop new
chemistries that allow the reversible attachment of peptide and proteins to biomaterial
scaffolds.
We will particularly focus on the development of novel conjugation chemistries that allow
proteins to be covalently attached to material surfaces via stabilised imines. We will identify
conditions that allow subsequent cleavage of the protein under biocompatible conditions,
while regenerating the original reactive groups on the material surface. By doing so, we will
enable the attachment of a second signalling protein that can itself be cleaved, allowing
iterative cycles of protein presentation. This would represent a major advance in biomaterials
chemistry, allowing us to take a major step towards mimicking the complexity of natural
tissues. Key to this goal is the optimisation of the underlying conjugation chemistry, requiring
precise understanding of the reaction equilibria and kinetics which we will study using a
combination of photo-physical and materials chemistry techniques. We will then go on to
apply our novel chemistries in the design of new biomaterials for cartilage regeneration, by
sequentially presenting growth factor signalling proteins that drive tissue development from
cell growth through to tissue maturation.
