Cavitation bubbles form in soft biological systems when subjected to a negative pressure above a critical threshold, and dynamically change their size and shape in a violent manner. The critical threshold and dynamic response of these bubbles are known to be sensitive to the mechanical characteristics of highly compliant biological systems. Several recent studies have demonstrated different biological implications of cavitation events in biological systems, from therapeutic drug delivery and microsurgery to blunt injury mechanisms. Due to the rapidly increasing relevance of cavitation in biological and biomedical communities, it is necessary to review the current state-of-the-art theoretical framework, experimental techniques, and research trends with an emphasis on cavitation behavior in biologically relevant systems (e.g., tissue simulant and organs). In this review, we first introduce several theoretical models that predict bubble response in different types of biological systems and discuss the use of each model with physical interpretations. Then, we review the experimental techniques that allow the characterization of cavitation in biologically relevant systems with in-depth discussions of their unique advantages and disadvantages. Finally, we highlight key biological studies and findings, through the direct use of live cells or organs, for each experimental approach.

The dynamic response of cells when subjected to mechanical impact has become increasingly relevant for accurate assessment of potential blunt injuries and elucidating underlying injury mechanisms. When exposed to mechanical impact, a biological system such as the human skin, brain, or liver is rapidly accelerated, which could result in blunt injuries. For this reason, an acceleration of greater than > 150 g is the most commonly used criteria for head injury. To understand the main mechanism(s) of blunt injury under such extreme dynamic threats, we have developed an innovative experimental method that applies a well-characterized and -controlled mechanical impact to live cells cultured in a custom-built in vitro setup compatible with live cell microscopy. Our studies using fibroblast cells as a model indicate that input acceleration ( $${a}_{in}$$ain ) alone, even when it is much greater than the typical injury criteria, e.g., $${a}_{in}>1{,}000$$ain>1,000 g, does not result in cell damage. On the contrary, we have observed a material-dependent critical pressure value above which a sudden decrease in cell population and cell membrane damage have been observed. We have unambiguously shown that (1) this critical pressure is associated with the onset of cavitation bubbles in a cell culture chamber and (2) the dynamics of cavitation bubbles in the chamber induces localized compressive/tensile pressure cycles, with an amplitude that is considerably greater than the acceleration-induced pressure, to cells. More importantly, the rate of pressure change with time for cavitation-induced pressure is significantly faster (more than ten times) than acceleration-induced pressure. Our in vitro study on the dynamic response of biological systems due to mechanical impact is a crucial step towards understanding potential mechanism(s) of blunt injury and implementing novel therapeutic strategies post-trauma.