Posters to be Presented:

Tissue Bond Strength and Intraluminal Temperature

as a Function of Applied Fusion Pressure

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Anderson, N.S., Kramer, E., Cezo, J., Ferguson, V.L., Rentschler, M.E.

In the clinical use of thermal tissue fusion, which uses heat and pressure to fuse arterial tissues, the input parameters of applied pressure, fusion temperature, and duration of energy input have largely been optimized through trial and error. The objective of this work is to experimentally elucidate the effect applied pressure has on bond strength and internal tissue temperature during fusion. The outcomes will aid in further characterization of the bond between thermally fused tissues which may direct the design of future thermal fusion devices.

The role of applied pressure was investigated by fusing porcine splenic arteries at applied loads ranging from 10-500 N. Pressure was applied to the arteries using a standard uniaxial tensile testing system to maintained a prescribed force (MTS Insight II). To achieve fusion, an input heat of 170° C was applied for 3.0 s via aluminum nitride heaters which were mounted to the MTS using custom fixtures. Fusion strength was then evaluated using burst pressure testing, which measures the intraluminal pressure at which a thermal bond fails. Intraluminal temperature was measured in a separate procedure with an array of five thermocouples inserted into the artery lumen during fusion [1]. Finally, samples of fused arteries from each applied load were histologically assessed following Hematoxylin & Eosin staining.

The fused vessels exhibited a peak in burst pressure for an applied load of 35 N before falling to a near constant value at higher loads (Figure 1). The intraluminal temperature measurements largely increased with increasing applied pressure. Based on the histological images, the peak in fusion strength corresponds to fusions between the media layers of the vessel, while the fall and plateau occurs when the media ruptures out of the fusion region and bonds form between the adventitia layers. These results indicate that an applied load of approximately 35 N is optimal for thermal fusion, a previously undetermined value as most commercial fusion devices apply loads around 100 N. The results also suggest that media fusions are stronger than adventitia fusions; the particular compounds or ratio of compounds that allow media to form stronger fusions merits further investigation.

Cezo, J.D., Kramer, E., Taylor, K., Ferguson, V., Rentschler, M.E., "Temperature Measurement Methods during Direct Heat Arterial Tissue Fusion," IEEE Trans on Biomedical Engineering. 60(9):552-2558, 2013.

Synthesis of Well-Controlled Nanogels via Block Copolymer Self-Assembly:

A Systematic Characterization of the Properties and Potential Applications

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Christina K. Uhlir

In the United States there is a growing need for materials that can probe and fight diseases of the heart, brain, and body as a whole. In this study nanogels, block copolymers, and copolymers were synthesized using solution polymerization and directed self-assembly. Results indicate that the nanogels are highly responsive to changes in pH and temperature and they are of a size (29 nanometers) that makes them viable drug delivery devices. Additionally, these nanogels macrogel at very low nanogel concentrations (10 – 15 weight %), which makes them reasonable candidates for dental repairs and enhancements. The present study also characterizes the process by which these nanogels and their precursors (block copolymers and copolymers) were synthesized. Our findings illustrate that solution polymerization followed by self-assembly is the most appropriate synthetic pathway for the synthesis of nanogels required for biomedical and dental interventions because the process allows the nanogels to retain the selected behavioral characteristics of the block copolymer and copolymer and, as this study specifically demonstrates, enhance certain copolymer and block copolymer traits. The copolymer, block copolymer, and nanogels that were synthesized in this study, therefore, could potentially be used to help researchers understand and treat some of the more deleterious illnesses such as Alzheimer’s disease, post-traumatic stress disorder, and Type II diabetes.

Uhlir, Christina, "Synthesis of Well-Controlled Nanogels via Block Copolymer Self-Assembly: A Systematic Characterization of the Properties and Potential Applications," University of Colorado at Boulder, 2013.

Gold nanoparticle templated microbubbles for enhanced photoacoustic and ultrasound imaging

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Jacob D. Dove, Todd W. Murray and Mark A. Borden

Medical imaging contrast agents have improved the ability to detect and treat diseased tissue. Two agents that have seen widespread use for contrast enhanced imaging are plasmonic nanoparticles for photoacoustics and microbubbles for ultrasound. Nanoparticles offer enhanced photoacoustic contrast due to their strong optical absorption, and microbubbles increase ultrasound contrast through efficient scattering around resonance. We report on a novel gold nanoparticle-coated microbubble (AuMB) capable of enhancing both ultrasound and photoacoustic contrast. AuMBs were comprised of 5 nm gold nanospheres coated to the surface of size selected, lipid-encapsulated microbubbles through a biotin-avidin coupling scheme. Nanoparticle surface density was controlled through the amount of biotinylated lipid incorporated into the microbubble shell. Upon illumination with a pulsed laser source, solutions of AuMBs produced a much larger photoacoustic response than solutions of nanoparticles alone. Ultrasound and photoacoustic images of an agarose flow-through tissue phantom were acquired. AuMBs solutions produced strong contrast in both the ultrasound and photoacoustic images. The photoacoustic response of single AuMBs was studied using a modified optical microscope, in which an individual AuMB was excited with a pulsed laser and the bubble wall radius was tracked using light scattering. It was found that pulsed laser illumination caused individual AuMBs to be driven into resonance, potentially allowing for efficient photoacoustic emission at the resonance frequency and producing the signal enhancement observed in the AuMB solutions.

Improving sonoporative efficiency through use of size isolated microbubbles

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Alexander Fan

While viral therapeutics promise a highly efficient means of transfecting suspended cells such asleukocytes, safety concerns have pushed interest towards less efficient non-viral therapeutics. In vitro studies have demonstrated that porative transfection methods such as electroporation and microbubble-assisted sonoporation (MAS) offer superior transfection rates in previously difficult-to-transfect cells. While current use of electroporation is limited to in vitro applications, there have been a handful of translational studies examining the performance of MAS in vivo. While MAS is considered to be safe and offers a high level of spatial and temporal control over treatment regimes, further improvements to transfection efficiency are desirable for therapeutic applications. Optimization studies in the field of MAS have previously examined the effect of ultrasonic parameters on drug uptake and viability. In this study, we aim to improve MAS drug delivery to suspended cells by studying the effect of microbubble size.

Poly(lactic acid) microbubbles as stable porogens for tissue engineered scaffolds

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P. A. Mountford, S. R. Sirsi, I. M. Baus, E. J. Kinzie, S. A. Etezazian, E. G. Lima, C. T. Hung, and M. A. Borden

Current biocompatible hydrogel scaffolds for tissue engineering lack spatiotemporal control over nutrient transport to cells following cellular deposition of extracellular matrix. Lima et al.1 recently showed that microporous scaffolds constructed by the dissolution of lipid shelled microbubbles, which were seeded into the gel along with articular chondrocyte cells, can promote nutrient transport and increase engineered cartilage stiffness (Young’s modulus) by twofold. Although lipid shelled microbubbles are a sufficient porogen for hydrogel scaffolds for up to one week, the shell lacks the stability necessary for long-term control over nutrient transport. To address this, we engineered tissue scaffolds seeded with poly(lactic acid) (PLA) shelled microbubbles, which have greater stability compared to lipid shelled microbubbles owing to increased shell thickness and rigidity. We reasoned that because PLA microbubbles are more stable to dissolution, they can provide enhanced and prolonged control over nutrient transport. We therefore hypothesized that nutrient transport could be facilitated over a longer period (>2 weeks) in gels containing microbubbles coated with PLA versus lipids. We also hypothesized that high intensity focused ultrasound (HIFU) can be used to improve control over the spatial distribution of hydrogel pores.