Dr Jonathan Dawson (School of Human Development and Health, University of Southampton)
Dr Agnieszka Janeczek (Renovos Biologics Limited); Prof Richard Oreffo (School of Human Development and Health, University of Southampton)
Nanoclays offer new possibilities for medicine due to their ability to assemble gels, promote cellular ingrowth and bind biological molecules. We have developed injectable nanoclays gels that set in the body and harness potent growth-factors to induce bone formation with greater precision and safety. Renovos Biologics® was spun out from the university in 2017 to pursue the translation of this technology for bone fusion and other regenerative applications. Immune cells such as macrophages, play a key role in mediating the colonisation of clay gels by stem cells yet little is known about the interaction of these cells with nanoclays. We have evidence to indicate that the surface properties of nanoclays underlie their bioactivity via protein adsorption and subsequent cell response. This project will test the hypothesis that nanoclays of different size and surface charge will effect early immune cell responses differently which in turn will influence later bone formation. Learning how nanoclay properties effect immune cells will allow us to optimise nanoclay formulations to improve bone repair therapies. These mechanistic questions are also crucial to define the regulatory safety requirements ahead of clinical trials. In collaboration with Renovos the student will synthesise nanoclay in the Renovos clay lab and develop new formulations designed to explore the intersecting influences of surface area (high, standard, low) and charge (high, standard, low) on surface reactivity and cell response. These will be analysed within the FoM for ectopic bone induction using 3D fluorescence imaging of macrophage recruitment in vivo combined with correlative high-resolution microCT analysis of progressive bone formation to allow quantitative longitudinal analysis of this critical interaction. Parallel in vitro and ex vivo (whole blood) studies of cell and protein interactions will provide mechanistic insights into early inflammatory events and establish a predictive ex vivo assay for subsequent refinement of biomaterial chemistry.