.From ultrasound imaging to blood pressure monitoring and tissue engineering with coated bubbles: rheology, jetting, and microstreaming*

Intravenously injected microbubbles are used as contrast-enhancing agents in diagnostic ultrasound imaging. They are coated by a nanometer-thick shell of lipids, proteins, or polymers which stabilizes them against premature dissolution. In 2003, we proposed that the shell be modeled as an interface with intrinsic interfacial rheology, characterized by properties such as interfacial viscosities and elasticities, in contrast to as a layer with bulk rheological properties. We applied models to commercial contrast agents, determined the values of their characteristic interfacial properties, and validated the model using in vitro acoustic experiments. We developed a hierarchical approach to contrast agent modeling where models were progressively refined as warranted by validating experiments and the underlying physics. We have built an in-house facility for synthesizing lipid-coated microbubbles and micro- and nanodroplets of volatile perfluorocarbon liquid, and have been investigating fundamental phenomena such as acoustic droplet vaporization (ADV) and bioeffects of ultrasound and microbubbles in cancer therapy and stem cell tissue engineering. The talk will be an overview of our research emphasizing recent efforts on microbubbles and ultrasound-assisted bone and cartilage tissue engineering in 3D-printed scaffolds. Low-intensity pulsed ultrasound (LIPUS) in conjunction with microbubbles has been shown in our lab to facilitate bone and cartilage formation from mesenchymal stem cells. We will discuss nonlinear shape oscillations of microbubbles and acoustic microstreaming that are responsible for such bioeffects. We studied them using boundary element (BEM) simulation and perturbative analysis of an encapsulated microbubble near a vessel wall.