Characterisation of ceramic bone graft environments for optimised angiogenesis

There has been significant interest over a number of years in the use of calcium phosphate implants for skeletal repair due to their similarity in composition to the mineral component of the hard tissues in the body. However, the efficacy of bone graft substitutes is strongly influenced by their ability to support tissue in-growth and encourage angiogenesis. Previous work done by Gariboldi et al. on the 3D printing of controlled hydroxyapatite architectures as model substrates to study angiogenesis has resulted in the successful establishment techniques not only relating to the 3D printing of such substrates but also to culture the appropriate combination of cells to produce aligned micro-vessels. This result gives rise to a significant number of new ideas and possibilities to further the research area.

The control of surface roughness and pore structure has recently become a very hot topic in the field of biomaterials and bioceramics field in terms of the effects on protein adsorption (e.g. from plasma). Preliminary studies will assess the nature of protein adsorption and their release kinetics. The work will move on to consider how this influences osteoclastic remodelling and osteoblast-mediated bone deposition. While mono-culture has often been used in the past, the importance of co-culture of the physiologically relevant cells is increasingly recognised as a way to provide improved understanding of the underlying mechanisms and processes of bone repair. The use of highly controlled, model 2.5D environments offers the potential to study in more detail the effects of scaffold architecture and surface roughness for the development of angiogenic and osteo-inductive bone graft substitutes.

Furthermore, I intend to translate the findings made in 2.5D to the more challenging aspects of production of controlled 3D environments as part of this project. Over the course of the project, I seek to develop my expertise in live cell imaging to understand cell-cell interactions. Additionally, I will develop the skills and knowledge readily available in the research group, and explore how X-Ray microtomography (microCT) might be combined with the use of appropriate contrast agents. These include antibody conjugates for evaluation of angiogenesis and more broadly, to provide information about the role of the protein adsorption in bone repair.

The outcome of the investigations will be an improved understanding of the influence of protein adsorption on bone graft substitutes on bone repair and further insights into the role of scaffold architecture and surface topography in directing cell behaviour.