A physical model to investigate the acoustic behaviour of microbubbles and nanodroplets within a bone fracture

Impaired fracture healing is a major financial burden for healthcare services; 5%–10% of bone fractures result in non-unions, and there is no clinically approved systemic therapy. This study characterises acoustically stimulated microbubbles (MBs) and nanodroplets (NDs) as non-invasive ultrasound responsive vehicles for the targeted delivery of osteogenic compounds. A microscope-compatible water-tank incorporating a passive cavitation detector was developed to study the acoustic behaviour of MBs and NDs within physical models of bone fractures (gap: 3.5–5.5 mm, angles: 0 deg and 90 deg). The device was designed using COMSOL Multiphysics (Burlington, MA) and tested in-vitro. The bone was simulated using a material with comparable acoustic impedance (Sawbones, WA). Numerical simulations showed that the developed experimental set-up generated a relatively uniform acoustic field at a target plane. It could be operated at either 1 or 2 MHz US frequency, at an acoustic pressure in the range 0–1 MPa. The inclusion of a fracture model caused perturbations to the acoustic field, which were dependent on the architecture of the fracture (i.e., relative to the incident US field). Ongoing studies are investigating how these perturbations affect ND/MB response in-vitro. Further studies will investigate the relationship between MB/ND acoustic response and the release of biologically active compounds.