Acoustic Droplet Vaporization in Acoustically Responsive Scaffolds: Effects of Frequency of Excitation, Volume Fraction and Threshold Determination Method.

Ultrasound-induced vaporization of liquid perfluorocarbon (PFC) droplets into microbubbles, termed acoustic droplet vaporization (ADV), has potential therapeutic and diagnostic applications. Recently, we demonstrated how ADV-a threshold-based phenomenon-can modulate the release of biomolecules from composite hydrogels, thereby stimulating regenerative processes, such as angiogenesis. These composite hydrogels, called acoustically responsive scaffolds (ARSs), consist of monodispersed, micron size PFC emulsions embedded within a fibrin matrix. This study investigated the effects of frequency of excitation (2.25, 5, 7.5 and 10 MHz) and volume fraction (0.05%, 0.2% and 1% [v/v]) of monodispersed, double emulsions in the ARSs on the ADV threshold. We determined and compared the ADV thresholds via acoustic methods, including active detection, passive detection and attenuation, as well as an echogenicity-based method using B-mode imaging. The ADV threshold determined via these four techniques showed an increasing trend with frequency of excitation. Further analysis of the wave propagation showed that the amplitudes of high frequency harmonics were diminished in ARSs with high volume fractions of emulsion. The ADV threshold inversely correlated with the volume fraction of emulsion at the lowest excitation frequency. However, at higher frequencies, possibly due to the high acoustic reflectivity of the PFC emulsions, the ADV threshold correlated directly with the volume fraction of the emulsion. Additionally, the ADV efficiency correlated with the supra-threshold acoustic pressure. Overall, these results elucidate fundamental acoustic properties of the ARSs, which can be used in future applications.