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

Abstract

Impaired fracture healing causes a major financial burden for healthcare services;10% of bone fractures result in costly and debilitating conditions like delayed ornonunion fractures. Common treatments are invasive, with a significant impact on apatient’s quality of life. In this study, we aim to overcome this limitation by usingacoustically-stimulated microbubbles (MBs) and nanodroplets (NDs) as non-invasiveultrasound responsive vehicles for the targeted delivery of osteogenic compounds.MBs and NDs safety and efficacy depend on their size and stability; in this study,formulation protocols were optimised and the effects of production, storage andhandling parameters assessed. A microscope-compatible water-tank incorporating apassive cavitation detector was also developed to study the acoustic behaviour of MBsand NDs within a model bone fracture.A method was established to produce MBs and NDs, which were stable uponstorage. The optimal formulation conditions for MBs were to produce them in abiocompatible viscous medium, store them at low temperature (4oC) and label themwith DiI at a concentration < 2.14 μM. As for NDs, the optimal conditions wereto produce them with a percentage of PFP equal to 10% v/v and to perform thesonication step for 60 seconds with an intensity of 72 W to achieve a narrow sizedistribution. MBs cavitation and NDs vaporisation were achieved and evaluated usingthe developed acoustic stimulation apparatus.Further studies will investigate the relationship between MB and ND acousticresponse and the release of osteogenic compounds.

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