Ricerc@Sapienza

The proposal concerns development and modelling of a microfluidic platform to study cavitation enhanced endothelial permeability within the larger context of targeted drug delivery. The primary barrier drugs need to overcome to reach the target from the circulation is the endothelium which prevents drug from diffusing to the tissues. Cavitation enhanced permeability consists in injecting stabilised microbubbles which are locally activated by ultrasound. The ensuing dynamics exerts mechanical stress on the endothelium and facilitates the opening of the junctional complexes that held tight together the endothelial cells. The interest is motivated by the reversibility of the alteration, with permeability increased for a finite time window followed by recovery of preexistent physiological conditions. Improper protocols may however lead to endothelial damage and cell apoptosis. Hence the interest in a system where mechanical and biological parameters can be held under strict control. The platform we will realise consists of microfluidic channels functionalized with an endothelial layer grown under physiological shear rate and integrates microbubble generators able to finely control dispersity and properties of the injected microbubbles. In parallel, a novel photonic sensor is developed to measure the cavitation induced stress. The project is completed by the theoretical/numerical study of the essential aspects of cavitation enhanced permeability. The phase-field approach is exploited to model cavitation accounting for bubble coatings and the bending rigidity of the endothelium. The proposal exploits the PI's unique expertise in the field, testified by prestigious international awards like the ERC Adg Grant 2013 and the ERC Proof of Concept 2017 INVICTUS concerning cavitation in general and, more specifically, in bio-inspired microchips.