Exploring if Hypoxia-Mimicking Scaffolds Have a Proangiogenic Influence on Bone and Cartilage Tissue Development and/or Regeneration

The development and regeneration of bone and cartilage tissue, and the role of angiogenesis in these processes, are important topics in regenerative medicine. In tissue engineering, cell behaviour in vitro and in vivo can be affected by various stimuli, including changes in the extracellular chemical composition. Copper ions have been reported to have a proangiogenic effect (e.g. as CuSO4 added to endothelial cells in a 3D culture system) [1], and copper deficiency has been shown to result in teratogenicity [2]. Using an organotypic chick femur culture system, this PhD project will aim to identify if:

(a) delivery of copper ions to the developing femur affects bone tissue formation;

(b) if copper ions at a particular concentration range plays a proangiogenic role that supports endochondral bone formation; and

(c) if copper ions affect the transition of hypertrophic cartilage to mineralised bone through a hypoxia-mimicking mechanism, in particular through interactions with NO and HIF-1a.

The project offers multi-disciplinary training, and the labs involved have extensive experience with developing and characterising synthetic scaffolds for guiding tissue repair and for tissue engineering, and for utilizing chick embryo cultures as model systems to test the effects of various pharmacological compounds on skeletal development. The successful candidate would receive training in the characterisation of biomaterial scaffolds and substrates, cell culture and cell-material interactions, chick embryo cultures and tissue dissection, histological analysis and immunohistochemistry, imaging (light and fluorescence microscopy) and microcomputed tomography (uCT). Much of the work in our institution is very translational, so the student would also gain exposure to the considerations required to translate aspects of research towards potential clinical use.