In the last couple of decades, ultrasound-driven microbubbles have proven excellent candidates for local drug delivery applications. Besides being useful drug carriers, microbubbles have demonstrated the ability to enhance cell and tissue permeability and as a consequence, drug uptake herein. Notwithstanding the large amount of evidence for their therapeutic efficacy, open issues remain. Due to the vast amount of ultrasound- and microbubble-related parameters that can be altered, and the variability in different models, the translation from basic research to (pre-)clinical studies has been hindered. This review aims at connecting the knowledge gained from fundamental microbubble studies to the therapeutic efficacy seen in in vitro and in vivo studies, with an emphasis on a better understanding of the response of a microbubble upon exposure to ultrasound and its interaction with cells and tissues. More specifically, we address the acoustic settings and microbubble-related parameters i.e. bubble size and physico-chemistry of the bubble shell that play a key role in microbubble-cell interactions and in the associated therapeutic outcome. Additionally, new techniques that may provide additional control over the treatment, such as monodisperse microbubble formulations, tunable ultrasound scanners and cavitation detection techniques, are discussed. An in-depth understanding of the aspects presented in this work could eventually lead the way to more efficient and tailored microbubble-assisted ultrasound therapy in the future.

Ultrasound is extensively used in medical imaging, being safe and inexpensive and operating in real time. Its scope of applications has been widely broadened by the use of ultrasound contrast agents (UCAs) in the form of microscopic bubbles coated by a biocompatible shell. Their increased use has motivated a large amount of research to understand and characterize their physical properties as well as their interaction with the ultrasound field and their surrounding environment. Here we review the theoretical models that have been proposed to study and predict the behavior of UCAs. We begin with a brief introduction on the development of UCAs. We then present the basics of free-gas-bubble dynamics upon which UCA modeling is based. We review extensively the linear and non-linear models for shell elasticity and viscosity and present models for non-spherical and asymmetric bubble oscillations, especially in the presence of surrounding walls or tissue. Then, higher-order effects such as microstreaming, shedding and acoustic radiation forces are considered. We conclude this review with promising directions for the modeling and development of novel agents.

Reproduction of the anatomical structures and functions of tissues using cells and designed 3D scaffolds is an ongoing challenge. For this, scaffolds with appropriate biomorphic surfaces promoting cell attachment, proliferation and differentiation are needed. In this study, eight triply-periodic minimal surface (TPMS)-based scaffolds were designed using specific trigonometric equations, providing the same porosity and the same number of unit cells, while presenting different surface curvatures. The scaffolds were fabricated by stereolithography using a photocurable resin based on the biocompatible, biodegradable and rubber-like material, poly(trimethylene carbonate) (PTMC). A numerical approach was developed to calculate the surface curvature distributions of the TPMS architectures. Moreover, the scaffolds were characterized by scanning electron microscopy, micro-computed tomography and water permeability measurements. These original scaffold architectures will be helpful to decipher the biofunctional role of the surface curvature of scaffolds intended for tissue engineering applications.

When illuminated by a laser, plasmonic nanoparticles immersed in water can very quickly and strongly heat up, leading to the nucleation of so-called plasmonic vapor bubbles. While the long-time behavior of such bubbles has been well-studied, here, using ultrahigh-speed imaging, we reveal the nucleation and early life phase of these bubbles. After some delay time from the beginning of the illumination, a giant bubble explosively grows, and collapses again within 200 μs (bubble life phase 1). The maximal bubble volume $V_{max}$ remarkably increases with decreasing laser power, leading to less total dumped energy E. This dumped energy shows a universal linear scaling relation with $V_{max}$, irrespective of the gas concentration of the surrounding water. This finding supports that the initial giant bubble is a pure vapor bubble. In contrast, the delay time does depend on the gas concentration of the water, as gas pockets in the water facilitate an earlier vapor bubble nucleation, which leads to smaller delay times and lower bubble nucleation temperatures. After the collapse of the initial giant bubbles, first, much smaller oscillating bubbles form out of the remaining gas nuclei (bubble life phase 2). Subsequently, the known vaporization dominated growth phase takes over, and the bubble stabilizes (life phase 3). In the final life phase 4, the bubble slowly grows by gas expelling due to heating of the surrounding. Our findings on the explosive growth and collapse during the early life phase of a plasmonic vapor bubble have strong bearings on possible applications of such bubbles. Significance Plasmonic microbubbles are at the center of numerous applications, including micromanipulation/nanomanipulation, biomedical diagnosis and therapy, and solar energy harvesting. Controlling the dynamics of these microbubbles is key to successfully exploiting their potential in the growing number of applications. Literature has vastly overlooked the nucleation and early microsecond dynamics by which these microbubbles arise. It is of utmost importance to understand this early phase, as it displays the most violent dynamics and is the precursor and origin of all subsequent dynamics, on which the many applications rely.