• A two-way coupling interactions in the bubble–blood–vessel system is developed. • A dynamic model model of vessel injury is presented. • Ex vivo vascular model is applied to evaluate the degree of cell detachment by ultrasound-induced cavitation. • Shear stress contributes to vessel injury by cell detachment while normal stress mainly causes distention injury.

Experimental studies have shown that ultrasonic cavitation can reversibly open the blood-brain barrier (BBB) to assist drug delivery. Nevertheless, the majority of the present study focused on experimental aspects of BBB opening. In this study, we developed a three-bubble-liquid-solid model to investigate the dynamic behavior of multiple bubbles within the blood vessels, and elucidate the physical mechanism of drug molecules through endothelial cells under ultrasonic cavitation excitation. The results showed that the large bubbles have a significant inhibitory effect on the movement of small bubbles, and the vibration morphology of intravascular microbubbles was affected by the acoustic parameters, microbubble size, and the distance between the microbubbles. The ultrasonic cavitation can significantly enhance the unidirectional flux of drug molecules, and the unidirectional flux growth rate of the wall can reach more than 5 %. Microjets and shock waves emitted from microbubbles generate different stress distribution patterns on the vascular wall, which in turn affects the pore size of the vessel wall and the permeability of drug molecules. The vibration morphology of microbubbles is related to the concentration, arrangement and scale of microbubbles, and the drug permeation impact can be enhanced by optimizing bubble size and acoustic parameters. The results offer an extensive depiction of the factors influencing the blood-brain barrier opening through ultrasonic cavitation, and the model may provide a potential technique to actively regulate the penetration capacity of drugs through endothelial layer of the neurovascular system by regulating BBB opening.

Ultrasonic cavitation can damage surrounding material and be used for destruction of the target tissue. In this paper, we investigated the interaction between atherosclerotic plaque (AP) and cavitation bubbles to determine whether the mechanical effect of cavitation damage could be potentially useful in therapy for treating atherosclerotic plaques. A two-bubble–fluid–solid model was established to study the dynamic behavior of bubbles near the AP and the AP damage by ultrasound-induced cavitation. A low-intensity focused ultrasound (LIFU) transducer was used for testing cavitation-based AP damage. We found that the nonlinear oscillation of bubbles causes the relative positions of the bubbles to shift, either toward or away from one another, these phenomena lead to changes in the bond failure rate between the fiber bundles, and the value of BRF exhibits an upward trend, this is the reason why the fibers suffered from reversible stretching and compressing. However, the AP damage is irreversible and diminishes as the number of cycles in the ultrasonic burst. It appears that the bigger the radii, regardless of whether the bubble (3 − i)’s and bubble i's radii are equal, the greater the AP damage. Ultrasonic cavitation therapy may not be appropriate for advanced AP patients, and the calcified tissue has a greater impact on the stability of the plaque. The damage area should be strictly selected. Additionally, the tissue damage phenomenon was found in experimental results. This work shows that the severity of AP damage is correlated with acoustic parameters and the surrounding environment from both simulation and experimental perspectives. The results show that ultrasonic cavitation may provide a new choice for the treatment of AP.

The high selectivity of the vascular endothelium, exemplified by the blood-brain barrier (BBB), provides critical protection to tissues against harmful substances; however, it also severely restricts the targeted delivery of therapeutic agents, particularly large molecule drugs. Ultrasound-mediated microbubble cavitation has emerged as a promising strategy for enhancing drug delivery. However, conventional single-microbubble systems suffer from limitations, including uneven energy distribution and suboptimal permeabilization efficacy. Moreover, the synergistic mechanisms underlying dual-microbubble interactions within the microvasculature remain poorly understood. In this study, we developed a coupled two-microbubble fluid-solid system (TMFSS) model utilizing the finite element method to simulate the dynamic behavior of dual microbubbles within blood vessels under ultrasonic excitation. Our investigation focused on key parameters-including microbubble spacing, acoustic pressure amplitude, microbubble size, and shear-thinning blood rheology-and their effects on microbubble oscillation, microstreaming, vascular wall stress, and endothelial permeability. The results demonstrate that, compared with single-microbubble systems, the ultrasound-assisted TMFSS significantly enhances drug permeability. This synergistic permeabilization effect strongly depends on the acoustic parameters, blood viscosity, microbubble size, and spatial distribution. Our study quantitatively elucidates the structure‒activity relationship between TMFSS dynamics and drug penetration efficiency and presents a parameter optimization strategy for the precise modulation of vascular endothelial permeability.