No abstract

Laser induced cavitation is one of the effective techniques to generate controlled cavitation bubbles, both for basic study and for applications in different fields of engineering and medicine. Unfortunately, control of bubble formation and symmetry is hardly achieved due to a series of concurrent causes. In particular, the need to focus the laser beam at the bubble formation spot leads, in general, to a conical region proximal to the light source where conditions are met for plasma breakdown. A finite sized region then exists where the electric field may fluctuate depending on several disturbing agents, leading to possible plasma fragmentation and plasma intensity variation. Such irregularities may induce asymmetry in the successive bubble dynamics, a mostly undesired effect if reproducible conditions are sought for. In the present paper, the structure of the breakdown plasma and the ensuing bubble dynamics are analyzed by means of high speed imaging and intensity measurements of the shockwave system launched at breakdown. It is found that the parameters of the system can be tuned to optimize repeatability and sphericity. In particular, symmetric rebound dynamics is achieved almost deterministically when a pointlike plasma is generated at the breakdown threshold energy. Spherical symmetry is also favored by a large focusing angle combined with a relatively large pulse energy, a process which, however, retains a significant level of stochasticity. Outside these special conditions, the elongated and often fragmented conical plasma shape is found to be correlated with anisotropic and multiple breakdown shockwave emission.

Targeting pharmaceuticals through the endothelial barrier is crucial for drug delivery. In this context, cavitation‐assisted permeation shows promise for effective and reversible opening of intercellular junctions. A vessel‐on‐a‐chip is exploited to investigate and quantify the effect of ultrasound‐excited microbubbles—stable cavitation—on endothelial integrity. In the vessel‐on‐a‐chip, the endothelial cells form a complete lumen under physiological shear stress, resulting in intercellular junctions that exhibit barrier functionality. Immunofluorescence microscopy is exploited to monitor vascular integrity following vascular endothelial cadherin staining. It is shown that microbubbles amplify the ultrasound effect, leading to the formation of interendothelial gaps that cause barrier permeabilization. The total gap area significantly increases with pressure amplitude compared to the control. Gap opening is fully reversible with gap area distribution returning to the control levels 45 min after insonication. The proposed integrated platform allows for precise and repeatable in vitro measurements of cavitation‐enhanced endothelium permeability and shows potential for validating irradiation protocols for in vivo applications.

Immunotherapy is a powerful therapeutic approach able to re-educate the immune system to fight cancer. A key player in this process is the tumor microenvironment (TME), which is a dynamic...

Traditional drug delivery systems, where pharmaceutical agents are conveyed to the target tissue through the blood circulation, suffer of poor therapeutic efficiency and limited selectivity largely due to the low permeability of the highly specialised biological interface represented by the endothelial layer. Examples concern cancer therapeutics or degenerative disorders where drug delivery is inhibited by the blood-brain barrier (BBB). Microbubbles injected into the bloodstream undergo volume oscillations under localised ultrasound irradiation and possibly collapse near the site of interest, with no effect on the rest of the endothelium. The resulting mechanical action induces a transient increase of the inter-cellular spaces and facilitates drug extravasation. This approach, already pursed in in vivo animal models, is extremely expensive and time-consuming. On the other hand in vitro studies using different kinds of microfluidic networks are firmly established in the pharmaceutical industry for drug delivery testing. The combination of the in vitro approach with ultrasound used to control microbubbles oscillations is expected to provide crucial information for developing cavitation enhanced drug delivery protocols and for screening the properties of the biological interface in presence of healthy or diseased tissues. Purpose of the present review is providing the state of the art in this rapidly growing field where cavitation is exploited as a viable technology to transiently modify the permeability of the biological interface. After describing current in vivo studies, particular emphasis will be placed on illustrating characteristics of micro-devices, biological functionalisation, properties of the artificial endothelium and ultrasound irradiation techniques.