Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3–4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green–Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG’s effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation.
An abdominal aortic aneurysm (AAA) is a dilation of the abdominal segment of the largest artery in the body and can be accompanied by significant risk of rupture and mortality. The current treatment, surgical repair, carries risks and complications. As such, there is need for less invasive therapies capable of curbing aneurysm growth. Here we use an AAA mouse model to evaluate the potential of pentagalloyl glucose (PGG) to suppress aneurysm growth. To induce aneurysms, 5.0 mg/mL pancreatic porcine elastase (PPE) was topically applied to the infrarenal aorta and 0.2% beta aminoproprionitrile was continuously administered via drinking water. Four of the eight animals also received topical treatment of 0.06% PGG via gauze before PPE treatment. High frequency ultrasound imaging (Vevo2100 system, VisualSonics) with a MS550D transducer (40 MHz center frequency) was performed prior to surgery, and every week thereafter for 4 weeks. PGG-treated animals had a small but nonsignificant decrease (p = 0.09) in effective maximum aortic diameter on days 7 and 14 that was not present on day 28. Current work is being performed to quantify PGG binding via histological characterization. Ultimately, we aim to investigate the parameters required for PGG to be an effective treatment for mechanically-stabilizing small AAAs.
A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.
The diminutive size of
microrobots makes them advantageous for minimally invasive operations and
precise, localized treatment. One such application is aiding in localized drug delivery
for colorectal cancer as microrobots could offer reduced patient trauma, lower
risk of side effects, and higher drug retention rates. In this study, we
evaluate the abilities of a magnetic microrobot in a variety of conditions
using a high frequency ultrasound system. Under the influence of an external
rotating magnetic field, the microrobot tumbles end-over-end to propel itself
forward. Cytotoxicity tests demonstrated the constituent materials of
polydimethylsiloxane (PDMS) and SU-8 were nontoxic to murine fibroblasts. Then,
we quantified robot locomotion in an ex vivo porcine colon, testing the
materials, the tumbling orientation, and three magnet rotation frequencies.
Significant differences were found between materials and tumbling orientation,
revealing that SU-8 lengthwise microrobots were the fastest with an average
velocity of 2.12±0.25mm/s at a frequency of 1Hz. With this finding, the next
tests were completed at 1Hz frequency with SU-8 lengthwise microrobots. We used
in vitro agarose gels to maneuver the
robot through a variety of trajectories, tested the microrobots in situ and in vivo murine colons as well. Average velocities were calculated
for all tests with the in vivo murine
colon tests finding an average velocity of 2.07±0.05mm/s. Finally, the
microrobots were coated with a fluorescein payload and were shown to release a
payload over a one-hour time period. These findings suggest microrobots are
promising for targeted drug delivery and other in vivo biomedical applications.
Abstract A microrobot system comprised of an untethered tumbling magnetic microrobot, a two degree of freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro , in situ , and in vivo conditions, as well as a porcine colon in ex vivo conditions. High frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a one hour time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.
This paper presents a magnetic microrobot that demonstrates the ability to travel through wet conditions inside a murine colon. Under the influence of an external rotating magnetic field, it tumbles end-over-end to propel itself forward. The microrobot's real-time position can be accurately tracked using ultrasound imaging to help guide it to a desired target location. Diffusion tests were conducted and show that the microrobot releases a fluorescein payload over a two hour time period when it is applied as a coating. Cytotoxicity tests demonstrated that the microrobot's SU-8 body doped with magnetic NdFeB particles is also biocompatible with murine fibroblasts. The microrobot's capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.
Cardiac hypertrophy is abnormal thickening, followed by dilation, of the heart which can lead to congestive heart failure. Herein, we use a mouse model of hypertrophy to explore the relationship between in vivo strain and the resultant hypertrophic state. To do so, osmotic pumps containing saline (n = 5) or angiotensin II (AngII; n = 10) were surgically implanted into the dorsal flank of C57BL/6J mice. AngII increased blood pressure and cardiac afterload, causing myocardial hypertrophy. Mice were imaged weekly using a VisualSonics Vevo2100 ultrasound system with a MS550D transducer (40 MHz center frequency) to collect ECG-gated Kilohertz Visualization data. In combination with a linear stepper motor, we also collected four dimensional (4D) cardiac data (3D + time). Two weeks post-surgery, pumps were removed from a subset of mice to assess the heart’s ability to repair itself post-insult (n = 5). All mice were euthanized at 4 weeks. Standard metrics of left ventricular mass measured via two-dimensional slices of the 4D data indicated significantly increased mass in the AngII mice by day 14. Removal of the pump enabled significant, but partial, recovery. Current work is being performed to calculate strain within the cardiac wall. Ultimately, we aim to determine if increases in in vivo strain precede increases in cardiac mass.
Arterial aneurysms are pathological dilations of blood vessels which can be of clinical concern due to thrombosis, dissection, or rupture. Aneurysms can form throughout the arterial system, including intracranial, thoracic, abdominal, visceral, peripheral, or coronary arteries. Currently, aneurysm diameter and expansion rates are the most commonly used metrics to assess rupture risk. Surgical or endovascular interventions are clinical treatment options, but are invasive and associated with risk for the patient. For aneurysms in locations where thrombosis is the primary concern, diameter is also used to determine the level of therapeutic anticoagulation, a treatment that increases the possibility of internal bleeding. Since simple diameter is often insufficient to reliably determine rupture and thrombosis risk, computational hemodynamic simulations are being developed to help assess when an intervention is warranted. Created from subject-specific data, computational models have the potential to be used to predict growth, dissection, rupture, and thrombus-formation risk based on hemodynamic parameters, including wall shear stress, oscillatory shear index, residence time, and anomalous blood flow patterns. Generally, endothelial damage and flow stagnation within aneurysms can lead to coagulation, inflammation, and the release of proteases which alter extracellular matrix composition, increasing risk of rupture. In this review, we highlight recent work that investigates aneurysm geometry, model parameter assumptions, and other specific considerations that influence computational aneurysm simulations. By highlighting modeling validation and verification approaches, we hope to inspire future computational efforts aimed at improving our understanding of aneurysm pathology and treatment risk stratification.
We are introducing a wireless and passive strain sensing scheme that utilizes ultrasound imaging of a highly stretchable hydrogel embedded with zinc oxide (ZnO) nanoparticles, named "ZnO-gel". The incorporation of ZnO nanoparticles into a polymer network of the hydrogel improves both its elasticity and strength. It also serves as an ideal biocompatible ultrasound contrast agent that allows remote interrogation of the changes in volume or dimensions of the hydrogel in response to mechanical strains through simple ultrasound imaging. A systematic study of various ratios of ZnO nanoparticle fillers (ranging from 0 to 40% w/w), cross-linked within the poly (DMA-co-MAA) hydrogel, was performed to identify the appropriate ZnO-to-gel ratio that provided the optimal mechanical and ultrasound imaging properties. The results of these investigations showed that 10% w/w of ZnO nanoparticles provided the highest stretchability of 260% with the effective amount of contrast agents to achieve clear visibility of the hydrogel dimension during ultrasound imaging. In general, the applied strain deforms the ZnO-gel specimens by reducing the cross-sectional area at a linear rate of 0.24% area change per % of applied strain for strain levels of up to 250%. Biocompatibility tests with stromal cells (fibroblasts) did not show any acute toxicity of the hydrogel and the ZnO nanoparticles used in this technology. It is anticipated that this technology can be applied to a broad range of wireless and passive monitoring of physiological functions for which microenvironmental strain matters throughout the body, simply by tuning both the mechanical properties of the hydrogel and ZnO nanoparticle concentration.
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