Developing the NanoKick bioreactor to enable tissue engineered bone graft and use of metabolomics to identify bone specific drug candidates.

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Bone graft is regularly used in surgery (plastics, maxillofacial surgery and orthopaedics); bone is actually the second most grafted tissue after blood. Ideally the surgeon wishes to take bone from one area (donor site) to another area (recipient site) to support the operation they are performing. However, a patient's own donor bone is in short supply and its removal can lead to complications in the donor site. This means the surgeon will often recourse to allograft - decellularised (and thus biologically inferior) - bone from other people. A third, and growing, option is synthetic graft. Synthetic graft can be made from biologically active materials, but is not viable and thus not yet as good as living bone. Our bioreactor, that supplies nanoscale 'kicks' to cells in culture can be used to convert mesenchymal stem cells (the stem cells of the bone, simple to isolate from a patient's iliac crest or fat tissue) to bone forming osteoblasts. It can achieve this with cells seeded into 3D environments such as gels or potentially synthetic graft materials. This thus allows us to envisage supply of living bone graft derived from a patient's own cells. The ability to supply such materials would provide a new gold standard for bone grafting.In this project we will thus develop our bioreactor into a flexible platform for study of bone regeneration (which will also be of significant interest to many academic labs in the field) and provision of bone graft. Further to this vision of tissue engineered bone supply, there is also a big need in Pharma for relevant bone models to reduce use of both standard lab models that are very dissimilar to the in-body environment and animal testing which has large cost and ethical consideration. Our ability to produce 3D bone in the lab simply, reproducibly, at low cost and without need for chemical control of cell phenotype (we will just use the nanokicks) will provide an excellent model for testing of drugs for e.g. osteoporosis, osteogenesis imperfecta and other bone conditions. In this project, we will use our technique to study 3D bone formation in the lab and look at what metabolites, the basic building blocks of life, the cell use as they form bone. We will then identify bioactive metabolites and validate them in our bone mimics.Finally, we will test to see feasibility of applying nanokicks to humans to help treat e.g. spinal injury, slow bone repair and osteoporosis etc. We will move from mechanical nanokicks to acoustic nanokicks to achieve this.