A pre-clinical MRI-guided all-in-one focused ultrasound system for murine brain studies.

This paper describes the design and initial proof-of-concept of a single pre-clinical transcranial focused ultrasound (FUS) system capable of performing histotripsy (mechanical ablation), hyperthermia, blood-brain barrier opening (BBBO), sonodynamic therapy, or neuromodulation in a murine brain. We have termed it the All-in-One FUS system for murine brain studies, which is the first FUS system of its kind. The 1.

Experimental & numerical investigations of ultra-high-speed dynamics of optically induced droplet cavitation in soft materials.

Perfluorocarbon (PFC) droplets represent a novel class of phase-shift contrast agent with promise in applications in biomedical and bioengineering fields. PFC droplets undergo a fast liquid-gas transition upon exposure to acoustic or optical triggering, offering a potential adaptable and versatile tool as contrast agent in diagnostic imaging and localized drug delivery vehicles in therapeutics systems. In this paper, we utilize advanced imaging techniques to investigate ultra-high-speed inertial dynamics and rectified quasi-static (low-speed) diffusion evolution of optically induced PFC droplet vaporization within three different hydrogels, each of different concentrations, examining effects such as droplet size and PFC core on bubble dynamics and material viscoelastic properties.

Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels.

Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound.

Charge balanced aggregation: A universal approach to aqueous organic nanocrystals.

Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method.

Acoustically responsive scaffolds: Unraveling release kinetics and mechanisms for sustained, steady drug delivery.

Hydrogels can serve as local drug delivery depots that protect the biological activity of labile therapeutics. However, drug release from conventional hydrogels is typically rapid, which is not ideal for many therapeutic agents. We developed a composite hydrogel that enables sustained drug release in response to ultrasound.

The radial dynamics and acoustic emissions of phase-shift droplets are impacted by mechanical properties of tissue-mimicking hydrogels.

Acoustic droplet vaporization (ADV) offers a dynamic approach for generating bubbles on demand, presenting new possibilities in biomedical applications. Although ADV has been investigated in various biomedical applications, its potential in tissue characterization remains unexplored. Here, we investigated the effects of surrounding media on the radial dynamics and acoustic emissions of ADV bubbles using theoretical and experimental methodologies.

Ultra-high-speed dynamics of acoustic droplet vaporization in soft biomaterials: Effects of viscoelasticity, frequency, and bulk boiling point.

Phase-shift droplets are a highly adaptable platform for biomedical applications of ultrasound. The spatiotemporal response of phase-shift droplets to focused ultrasound above a certain pressure threshold, termed acoustic droplet vaporization (ADV), is influenced by intrinsic features (e.g.

Longitudinal Monitoring of Angiogenesis in a Murine Window Chamber Model .

Angiogenesis induced by growth factor administration, which can augment the blood supply in regenerative applications, has drawn wide attention in medical research. Longitudinal monitoring of vascular structure and development is important for understanding and evaluating the dynamics of involved biological processes. In this work, a dual-modality imaging system consisting of photoacoustic microscopy (PAM) and optical coherence tomography (OCT) was applied for noninvasive imaging of angiogenesis in a murine model.

Real-time spatiotemporal characterization of mechanics and sonoporation of acoustic droplet vaporization in acoustically responsive scaffolds.

Phase-shift droplets provide a flexible and dynamic platform for therapeutic and diagnostic applications of ultrasound. The spatiotemporal response of phase-shift droplets to focused ultrasound, via the mechanism termed acoustic droplet vaporization (ADV), can generate a range of bioeffects. Although ADV has been used widely in theranostic applications, ADV-induced bioeffects are understudied.

Acoustic droplet vaporization for on-demand modulation of microporosity in smart hydrogels.

Microporosity in hydrogels is critical for directing tissue formation and function. We have developed a fibrin-based smart hydrogel, termed an acoustically responsive scaffold (ARS), which responds to focused ultrasound in a spatiotemporally controlled, user-defined manner. ARSs are highly flexible platforms due to the inclusion of phase-shift droplets and their tunable response to ultrasound through a mechanism termed acoustic droplet vaporization (ADV).

Bubble nucleation and dynamics in acoustic droplet vaporization: a review of concepts, applications, and new directions.

The development of phase-shift droplets has broadened the scope of ultrasound-based biomedical applications. When subjected to sufficient acoustic pressures, the perfluorocarbon phase in phase-shift droplets undergoes a phase-transition to a gaseous state. This phenomenon, termed acoustic droplet vaporization (ADV), has been the subject of substantial research over the last two decades with great progress made in design of phase-shift droplets, fundamental physics of bubble nucleation and dynamics, and applications.

Ultrasound Contrast Stability for Urinary Bladder Pressure Measurement.

The goal of this study was to evaluate ultrasound contrast microbubbles (MB) stability during a typical cystometrogram (CMG) for bladder pressure measurement application using the subharmonic-aided pressure estimation technique. A detailed study of MB stability was required given two unique characteristics of this application: first, bulk infusion of MBs into the bladder through the CMG infusion system, and second, duration of a typical CMG which may last up to 30 min. To do so, a series of size measurement and contrast-enhanced ultrasound imaging studies under different conditions were performed and the effects of variables that we hypothesized have an effect on MB stability, namely, i) IV bag air headspace, ii) MB dilution factor, and iii) CMG infusion system were investigated.

Pressure Measurement in a Bladder Phantom Using Contrast-Enhanced Ultrasonography-A Path to a Catheter-Free Voiding Cystometrogram.

Objectives: The long-term goal of this study is to investigate the efficacy of a novel, ultrasound-based technique called subharmonic-aided pressure estimation (SHAPE) to measure bladder pressure as a part of a cystometrogram (CMG) in a urodynamic test (ie, pressure-flow study). SHAPE is based on the principle that subharmonic emissions from ultrasound contrast microbubbles (MBs) decrease linearly with an increase in ambient pressure. We hypothesize that, using the SHAPE technique, we can measure voiding bladder pressure catheter-free.

Multi-time scale characterization of acoustic droplet vaporization and payload release of phase-shift emulsions using high-speed microscopy.

Acoustic droplet vaporization (ADV) is the phase-transitioning of perfluorocarbon emulsions, termed phase-shift emulsions, into bubbles using focused ultrasound. ADV has been utilized in many biomedical applications. For localized drug release, phase-shift emulsions with a bioactive payload can be incorporated within a hydrogel to yield an acoustically-responsive scaffold (ARS).

Slow-Flow Ultrasound Localization Microscopy Using Recondensation of Perfluoropentane Nanodroplets.

Ultrasound localization microscopy (ULM) is an emerging, super-resolution imaging technique for detailed mapping of the microvascular structure and flow velocity via subwavelength localization and tracking of microbubbles. Because microbubbles rely on blood flow for movement throughout the vascular space, acquisition times can be long in the smallest, low-flow microvessels. In addition, detection of microbubbles in low-flow regions can be difficult because of minimal separation of microbubble signal from tissue.

Ultrasound-Induced Mechanical Compaction in Acoustically Responsive Scaffolds Promotes Spatiotemporally Modulated Signaling in Triple Negative Breast Cancer.

Cancer cells continually sense and respond to mechanical cues from the extracellular matrix (ECM). Interaction with the ECM can alter intracellular signaling cascades, leading to changes in processes that promote cancer cell growth, migration, and survival. The present study used a recently developed composite hydrogel composed of a fibrin matrix and phase-shift emulsion, termed an acoustically responsive scaffold (ARS), to investigate effects of local mechanical properties on breast cancer cell signaling.

Micropatterning of acoustic droplet vaporization in acoustically-responsive scaffolds using extrusion-based bioprinting.

Acoustically-responsive scaffolds (ARSs) are composite hydrogels that respond to ultrasound in an on-demand, spatiotemporally-controlled manner due to the presence of a phase-shift emulsion. When exposed to ultrasound, a gas bubble is formed within each emulsion droplet via a mechanism termed acoustic droplet vaporization (ADV). In previous and studies, we demonstrated that ADV can control regenerative processes by releasing growth factors and/or modulating micromechanics in ARSs.

Spatiotemporal control of myofibroblast activation in acoustically-responsive scaffolds via ultrasound-induced matrix stiffening.

Hydrogels are often used to study the impact of biomechanical and topographical cues on cell behavior. Conventional hydrogels are designed a priori, with characteristics that cannot be dynamically changed in an externally controlled, user-defined manner. We developed a composite hydrogel, termed an acoustically-responsive scaffold (ARS), that enables non-invasive, spatiotemporally controlled modulation of mechanical and morphological properties using focused ultrasound.

Release of basic fibroblast growth factor from acoustically-responsive scaffolds promotes therapeutic angiogenesis in the hind limb ischemia model.

Pro-angiogenic growth factors have been studied as potential therapeutics for cardiovascular diseases like critical limb ischemia (CLI). However, the translation of these factors has remained a challenge, in part, due to problems associated with safe and effective delivery. Here, we describe a hydrogel-based delivery system for growth factors where release is modulated by focused ultrasound (FUS), specifically a mechanism termed acoustic droplet vaporization.

Spatially-directed angiogenesis using ultrasound-controlled release of basic fibroblast growth factor from acoustically-responsive scaffolds.

Vascularization is a critical step following implantation of an engineered tissue construct in order to maintain its viability. The ability to spatially pattern or direct vascularization could be therapeutically beneficial for anastomosis and vessel in-growth. However, acellular and cell-based strategies to stimulate vascularization typically do not afford this control.

Stable and transient bubble formation in acoustically-responsive scaffolds by acoustic droplet vaporization: theory and application in sequential release.

Acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels containing monodispersed perfluorocarbon (PFC) emulsions, respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Previously, ADV has been used to control the release of bioactive payloads from ARSs to stimulate regenerative processes. In this study, we used classical nucleation theory (CNT) to predict the nucleation pressure in emulsions of different PFC cores as well as the corresponding condensation pressure of the ADV-generated bubbles.

Spatiotemporal control of micromechanics and microstructure in acoustically-responsive scaffolds using acoustic droplet vaporization.

Acoustically-responsive scaffolds (ARSs), which are composite fibrin hydrogels, have been used to deliver regenerative molecules. ARSs respond to ultrasound in an on-demand, spatiotemporally-controlled manner via a mechanism termed acoustic droplet vaporization (ADV). Here, we study the ADV-induced, time-dependent micromechanical and microstructural changes to the fibrin matrix in ARSs using confocal fluorescence microscopy as well as atomic force microscopy.

Spatially-directed cell migration in acoustically-responsive scaffolds through the controlled delivery of basic fibroblast growth factor.

Hydrogels are commonly used in regenerative medicine for the delivery of growth factors (GFs). The spatial and temporal presentations of GFs are critical for directing regenerative processes, yet conventional hydrogels do not enable such control. We have developed a composite hydrogel, termed an acoustically-responsive scaffold (ARS), where release of a GF is non-invasively and spatiotemporally-controlled using focused ultrasound.

Standing wave-assisted acoustic droplet vaporization for single and dual payload release in acoustically-responsive scaffolds.

An ultrasound standing wave field (SWF) has been utilized in many biomedical applications. Here, we demonstrate how a SWF can enhance drug release using acoustic droplet vaporization (ADV) in an acoustically-responsive scaffold (ARS). ARSs are composite fibrin hydrogels containing payload-carrying, monodispersed perfluorocarbon (PFC) emulsions and have been used to stimulate regenerative processes such as angiogenesis.

Local delivery of bone morphogenetic protein-2 from near infrared-responsive hydrogels for bone tissue regeneration.

Achievement of spatiotemporal control of growth factors production remains a main goal in tissue engineering. In the present work, we combined inducible transgene expression and near infrared (NIR)-responsive hydrogels technologies to develop a therapeutic platform for bone regeneration. A heat-activated and dimerizer-dependent transgene expression system was incorporated into mesenchymal stem cells to conditionally control the production of bone morphogenetic protein 2 (BMP-2).