In addition to the projects detailed below we work collaboratively with the European Commission Joint Research Centre, Ispra, Italy and the University of Tohoku, Sendai, Japan to study the regulation of bone cell activity by novel engineered biomaterials.
Designing bioactive polymeric biomaterial surfaces to regulate bone formationThe regulation of osteoblast activity is not only achieved through soluble and immobilised growth factors like bone morphogenetic proteins (BMPs) and vascular endothelial growth factors (VEGFs) but also by physical interaction with surface topography. This project aims to combine the delivery of potent osteogenic factors with the formation of a novel biomaterial surface that provides enhanced osteoblast differentiation and bone formation.
Interface protein engineering for the control of stem cell growth
This project investigates the potential for engineered proteins that can reproducibly self assemble into a monolayer on a surface (created in the laboratory of Prof. Jeremy Lakey) to regulate the commitment and differentiation of cells to the osteoblast lineage. Studies have demonstrated that cell adhesion and shape can be controlled by patterning using soft lithography, combinations of the recombinant proteins and thiol-terminnated PEGs. Experiments will now go on to investigate the relationship between immobilised cues and the control of osteogenesis.
Using heparin to regulate osteoblast activity
Bone morphogenetic proteins (BMPs) are powerful agents that stimulate the differentiation of cells to the osteoblast lineage increasing bone mass. However, their therapeutic use is limited by the need for large. This project investigates the potential for sulphated polysaccharides, like heparin, to potentiate BMP signalling. In vitro studies have shown that bone formation is increased in cultures of osteoblasts supplemented with heparin. In addition investigation of intracellular signalling events in cells simultaneously treated with BMP and heparin reveal significantly enhanced response. Further studies will begin dissect the role that heparin plays in regulating BMP signalling and investigate the potential for therapeutic heparins to influence BMP signalling.
Nanoscale control of cell activity on fabricated biomaterial surfaces
These studies will begin to dissect the role that extracellular environment plays in controlling the differentiation of bone marrow stromal cells. This objective will be addressed through studies that investigate how matrix extracellular phospho glycoprotein (MEPE) controls the activity of mediators such as PGE2 and BMP-2. Studies will then determine how spatial and molecular control of MEPE localisation in vitro influences its ability to control osteoblast differentiation before combining MEPE with biomaterial architecture to define an engineered extracellular environment.
