Bubbles for bone: acoustic stimulation for drug delivery in fracture repair

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In this studentship, we propose to attempt this by delivering ultrasound-responsive bubbles to the fracture site. Ultrasound stimulation of bubbles causes them to resonate. In our preliminary data, we have shown that this results in the release of bubble-associated drugs, improved uptake of compounds in nearby cells, and mechanostimulation of cells through either direct membrane interaction or via shear of extracellular media. More recently we have found that acoustically-responsive bubbles can be fabricated in the nanometre size range and that they accumulate at fracture sites (Figure 2). This means we will be able to localise drug-containing nanobubbles at bone fracture sites, before remotely stimulating them with ultrasound to both release their cargo and mechanostimulate the surrounding tissue. In this studentship, the student will first develop and optimise nanobubbles and ultrasound-responsive nanodroplet formulations (which cavitate to form microbubbles upon ultrasound stimulation) to demonstrate that these agents can simultaneously be used to deliver drugs and to mechanostimulate stem cells, inducing their differentiation in in vitro models. He or she will then determine which size and chemical characteristics lead to localisation of bubbles to the fracture callus post-injury. Finally, the student will test in vivo whether acoustic stimulation of fracture callus-localised bubbles affects the rate and quality of bone fracture healing. The student will train with experts in stem cell biology, mechanobiology, nanotechnology and ultrasonics from established experts at UoS, and with a collaboration with the University of Oxford (biomedical ultrasonics, biotherapy and biopharmaceuticals laboratory).