Biomedical Engineering and Bioengineering Commons^™

Thermally Assisted Pulsed Electric Field Ablation For Cancer Therapy, James Michael Hornef

Biomedical Engineering Theses & Dissertations

Pulsed Electric Fields (PEF) have promised improved treatment results in a variety of cancer types including melanoma, pancreatic and lung squamous cancer. Recent studies show that PEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. Experiments were performed to design, calibrate and implement a feedback-looped infrared laser irradiation system that could maintain specified temperatures during the treatment. The exact treatment area, penetration depth and thermal distribution of a 980-nm laser fiber were quantified using several methods, including the knife-edge technique and a tissue optical property study. In vivo and in vitro experiments using …

Treating A 20 Mm Hg Gradient Alleviates Myocardial Hypertrophy In Experimental Aortic Coarctation, David C. Wendell, Ingeborg Friehs, Margaret M. Samyn, Leanne Harmann, John F. Ladisa

Biomedical Engineering Faculty Research and Publications

Background

Children with coarctation of the aorta (CoA) can have a hyperdynamic and remodeled left ventricle (LV) from increased afterload. Literature from an experimental model suggests the putative 20 mm Hg blood pressure gradient (BPG) treatment guideline frequently implemented in CoA studies may permit irreversible vascular changes. LV remodeling from pressure overload has been studied, but data are limited following correction and using a clinically representative BPG.

Materials and methods

Rabbits underwent CoA at 10 weeks to induce a 20 mm Hg BPG using permanent or dissolvable suture thereby replicating untreated and corrected CoA, respectively. Cardiac function was evaluated at …

Protection By Inhaled Hydrogen Therapy In A Rat Model Of Acute Lung Injury Can Be Tracked In Vivo Using Molecular Imaging, Said H. Audi, Elizabeth R. Jacobs, Xiao Zhang, Amadou K.S. Camara, Ming Zhao, Meetha M. Medhora, Benjamin Michael Rizzo, Anne V. Clough

Biomedical Engineering Faculty Research and Publications

Inhaled hydrogen gas (H₂) provides protection in rat models of human acute lung injury (ALI). We previously reported that biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a rat model of ALI. Our objective was to evaluate the ability of ^99mTc-hexamethylpropyleneamineoxime (HMPAO) and ^99mTc-duramycin to track the effectiveness of H₂ therapy in vivo in the hyperoxia rat model of ALI. Rats were exposed to room air (normoxia), 98% O₂ + 2% N₂ (hyperoxia) or 98% O₂ + 2% H₂ (hyperoxia+H₂) for up to 60 …

Delivery Of Antioxidant And Anti-Inflammatory Agents For Tissue Engineered Vascular Grafts, Kenyatta S. Washington, Chris A. Bashur

Biomedical Engineering and Sciences Faculty Publications

The treatment of patients with severe coronary and peripheral artery disease represents a significant clinical need, especially for those patients that require a bypass graft and do not have viable veins for autologous grafting. Tissue engineering is being investigated to generate an alternative graft. While tissue engineering requires surgical intervention, the release of pharmacological agents is also an important part of many tissue engineering strategies. Delivery of these agents offers the potential to overcome the major concerns for graft patency and viability. These concerns are related to an extended inflammatory response and its impact on vascular cells such as endothelial …

Potency And Cytotoxicity Of A Novel Gallium-Containing Mesoporous Bioactive Glass/Chitosan Composite Scaffold As Hemostatic Agents, Sara Pourshahrestani, Ehsan Zeimaran, Nahrizul Adib Kadri, Nicola Gargiulo, Hassan Mahmood Jindal, Sangeetha Vasudevaraj Naveen, Shamala Devi Sekaran, Tunku Kamarul, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Chitosan-based hemostats are promising candidates for immediate hemorrhage control. However, they have some disadvantages and require further improvement to achieve the desired hemostatic efficiency. Here, a series of 1% Ga2O3-containing mesoporous bioactive glass-chitosan composite scaffolds (Ga-MBG/CHT) were constructed by the lyophilization process and the effect of various concentrations of Ga-MBG (10, 30, and 50 wt %) on the hemostatic function of the CHT scaffold was assessed as compared to that of Celox Rapid gauze (CXR), a current commercially available chitosan-coated hemostatic gauze. The prepared scaffolds exhibited >79% porosity and showed increased water uptake compared to that in CXR. The results …

New Fractals For Computer Generated Art Created By Iteration Of Polynomial Functions Of A Complex Variable, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Working Papers

Novel fractal forms can be created by iteration of higher order polynomials of the complex variable, z, with both positive and negative exponents, followed by optional integer power transformation, k zz . Such functions lead to an expanded universe of fascinating fractal patterns that can be incorporated into computer generated art.

Generalized Fractals For Computer Generated Art: Preliminary Results, Charles F. Babbs

Weldon School of Biomedical Engineering Faculty Working Papers

This paper explores new types of fractals created by iteration of the functions xn+1 = f1(xn, yn) and yn+1 = f2(xn, yn) in a general plane, rather than in the complex plane. Iteration of such functions generates orbits with novel fractal patterns. Especially interesting are N-th order polynomials, raised to a positive or negative integer power, p.

Such functions create novel fractal patterns, including budding, spiked, striped, dragon head, and bat-like forms. The present faculty working paper shows how to create a rich variety of complex and fascinating fractals using this generalized approach, which is accessible to students with high …

Cross-Species Complementation Reveals Conserved Functions For Early Flowering 3 Between Monocots And Dicots, He Huang, Malia A. Gehan, Sarah E. Huss, Sohpie Alvarez, Cesar Lizarraga, Ellen L. Gruebbling, John Gierer, Michael J. Naldrett, Rebacca K. Bindbeutel, Bradley S. Evans, Todd C. Mockler, Dmitri A. Nusinow

Nebraska Center for Biotechnology: Faculty and Staff Publications

Plant responses to the environment are shaped by external stimuli and internal signaling pathways. In both the model plant Arabidopsis thaliana (Arabidopsis) and crop species, circadian clock factors are critical for growth, flowering, and circadian rhythms. Outside of Arabidopsis, however, little is known about the molecular function of clock gene products. Therefore, we sought to compare the function of Brachypodium distachyon (Brachypodium) and Setaria viridis (Setaria) orthologs of EARLY FLOWERING 3, a key clock gene in Arabidopsis. To identify both cycling genes and putative ELF3 functional orthologs in Setaria, a …

Development Of Starch-Polyvinyl Alcohol (Pva) Biodegradable Film: Effect Of Cross-Linking Agent And Antimicrobials On Film Characteristics, Aniket Satish More, Chandani Sen, Madhusweta Das

Journal of Applied Packaging Research

To satisfy the need of developing eco-friendly flexible antimicrobial packaging film with minimum use of synthetic chemical ingredients, the present study examined the efficacy of citric acid (CA) as cross-linking agent and essential oils (EOs), viz., cinnamon essential oil (CEO) and oregano essential oil (OEO) as natural antimicrobials in corn starch-polyvinyl alcohol (CS-PVA) film. Compared to film prepared from filmogenic solution (FS) containing 75 kg CS+8.75 kg PVA+24.6 kg glycerol per m³ FS, film additionally containing CA at 0.07 kg/kg CS indicated 95% higher ultimate tensile strength (UTS) and 27% lower water vapor permeability (WVP). Film developed with incorporation …

An Optical Probe For Detecting Chondrocyte Apoptosis In Response To Mechanical Injury, Yihui Huang, Jun Zhou, Amirhossein Hakamivala, Jinglei Wu, Yi Hong, Joseph Borrelli Jr., Liping Tang

Bioengineering Faculty Publications - Archive

Cartilage injury induced by acute excessive contact stress is common and mostly affects young adult. Although early detection of cartilage injury may prevent serious and lifelong arthritic complications, early detection and treatment is not possible due to the lack of a reliable detection method. Since chondrocyte injury and subsequent cell death are the early signs of cartilage injury, it is likely that cartilage cell apoptosis can be used to predict the extent of injury. To test this hypothesis, a near infrared probe was fabricated to have high affinity to apoptotic cells. In vitro tests show that this apoptosis probe has …

The Effect Of Engineered Nanotopography Of Electrospun Microfibers On Fiber Rigidity And Macrophage Cytokine Production, Nicholas J. Schaub, Anthony R. D'Amato, Andrew Mason, David T. Corr, Erin Y. Harmon, Michelle R. Lennartz, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Currently, it is unknown how the mechanical properties of electro spun fibers, and the presentation of surface nano topography influence macrophage gene expression and protein production. By further elucidating how specific fiber properties (mechanical properties or surface properties) alter macrophage behavior, it may be possible to create electro spun fiber scaffolds capable of initiating unique cellular and tissue responses. In this study, we determined the elastic modulus and rigidity of fibers with varying topographies created by finely controlling humidity and including a non-solvent during electrospinning. In total, five fiber scaffold types were produced. Analysis of fiber physical properties demonstrated no …

Direct Numerical Simulation Of Turbulent Katabatic Slope Flows With An Immersed-Boundary Method, Clancy Umphrey, Ray Deleon, Inanc Senocak

Mechanical and Biomedical Engineering Faculty Publications and Presentations

We investigate a Cartesian-mesh immersed-boundary formulation within an incompressible flow solver to simulate laminar and turbulent katabatic slope flows. As a proof-of-concept study, we consider four different immersed-boundary reconstruction schemes for imposing a Neumann-type boundary condition on the buoyancy field. Prandtl’s laminar solution is used to demonstrate the second-order accuracy of the numerical solutions globally. Direct numerical simulation of a turbulent katabatic flow is then performed to investigate the applicability of the proposed schemes in the turbulent regime by analyzing both first- and second-order statistics of turbulence. First-order statistics show that turbulent katabatic flow simulations are noticeably sensitive to the …

Delayed Hypersensitivity To Nanosecond Pulsed Electric Field In Electroporated Cells, Sarah D. Jensen, Vera A. Khorokhorina, Claudia Muratori, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

We demonstrate that conditioning of mammalian cells by electroporation with nanosecond pulsed electric field (nsPEF) facilitates their response to the next nsPEF treatment. The experiments were designed to unambiguously separate the electroporation-induced sensitization and desensitization effects. Electroporation was achieved by bursts of 300-ns, 9 kV/cm pulses (50 Hz, n = 3–100) and quantified by propidium dye uptake within 11 min after the nsPEF exposure. We observed either sensitization to nsPEF or no change (when the conditioning was either too weak or too intense, or when the wait time after conditioning was too short). Within studied limits, conditioning never caused desensitization. …

Damage-Free Peripheral Nerve Stimulation By 12-Ns Pulsed Electric Field, Maura Casciola, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Modern technologies enable deep tissue focusing of nanosecond pulsed electric field (nsPEF) for non-invasive nerve and muscle stimulation. However, it is not known if PEF orders of magnitude shorter than the activation time of voltage-gated sodium channels (VGSC) would evoke action potentials (APs). One plausible scenario requires the loss of membrane integrity (electroporation) and resulting depolarization as an intermediate step. We report, for the first time, that the excitation of a peripheral nerve can be accomplished by 12-ns PEF without electroporation. 12-ns stimuli at 4.1-11 kV (3.3-8.8 kV/cm) evoked APs similarly to conventional stimuli (100-250 mus, 1-5 V, 103-515 V/m), …

Influence Of Fibroblasts On Functional Arteriogenesis In A Murine Chronic Hindlimb Ischemia Model, Ashli A. Santos

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) occurs when there is a narrowing or blockage – usually a buildup of plaque - within the arteries that reduces blood flow to tissues which can chronic ischemia. As with most diseases, early detection and proactive treatment are important to maximize prognosis. Exercise effectively treats PAOD, but due to ischemic pain in the limbs, or intermittent claudication (IC), exercise can become painful and difficult. Due to the buildup of plaque, occlusions create an ischemic environment that changes the pressure distribution in collateral networks and increases the shear stress in transverse collaterals. Those two responses signal …

Controllable Moderate Heating Enhances The Therapeutic Efficacy Of Irreversible Electroporation For Pancreatic Cancer, Chelsea M. Edelblute, James Hornef, Niculina I. Burcus, Thomas Norman, Stephen J. Beebe, Karl Schoenbach, Richard Heller, Chunqi Jiang, Sigi Guo

Bioelectrics Publications

Irreversible electroporation (IRE) as a non-thermal tumor ablation technology has been studied for the treatment of pancreatic carcinoma and has shown a significant survival benefit. We discovered that moderate heating (MH) at 43°C for 1-2 minutes significantly enhanced ex vivo IRE tumor ablation of Pan02 cells by 5.67-fold at 750 V/cm and by 1.67-fold at 1500 V/cm. This amount of heating alone did not cause cell death. An integrated IRE system with controllable laser heating and tumor impedance monitoring was developed to treat mouse ectopic pancreatic cancer. With this novel IRE system, we were able to heat and maintain the …

An Automated Workflow For Quantifying Rna Transcripts In Individual Cells In Large Data-Sets, Matthew C. Pharris, Tzu-Ching Wu, Xinping Chen, Xu Wang, David M. Umulis, Vikki M. Weake, Tamara L. Kinzer-Ursem

Weldon School of Biomedical Engineering Faculty Publications

Advanced molecular probing techniques such as single molecule fluorescence in situ hybridization (smFISH) or RNAscope can be used to assess the quantity and spatial location of mRNA transcripts within cells. Quantifying mRNA expression in large image sets usually involves automated counting of fluorescent spots. Though conventional spot counting algorithms may suffice, they often lack high-throughput capacity and accuracy in cases of crowded signal or excessive noise. Automatic identification of cells and processing of many images is still a challenge. We have developed a method to perform automatic cell boundary identification while providing quantitative data about mRNA transcript levels across many …

Identifying And Reducing Variability, Improving Scaffold Morphology, And Investigating Alternative Materials For The Blood Vessel Mimic Lab Electrospinning Process, Evan M. Dowey

Master's Theses

The work of the Cal Poly Tissue Engineering Lab is primarily focused on the fabrication, characterization, and improvement of “Blood Vessel Mimics” (BVMs), tissue engineered constructs used to evaluate cellular response to vascular medical devices. Currently, cells are grown onto fibrous, porous tubes made using an in-house electrospinning process from PLGA, a biocompatible co-polymer. The adhesion and proliferation of cells in a BVM is reliant on the micro-scale structure of the PLGA scaffold, and as such it is of great importance for the electrospinning process to consistently produce scaffolds of similar morphologies. Additionally, it has been shown that cell proliferation …

Mutagenesis Of Human Alpha-Galactosidase A For The Treatment Of Fabry Disease, Erin Stokes

Dissertations, Theses, and Capstone Projects

Fabry disease is an X-linked lysosomal storage disorder caused by the deficiency of the enzyme, α-galactosidase A, which results in the accumulation of the lipid substrate. This accumulation results in obstruction of blood flow in patients and early demise at approximately 40-60 years of age. There is currently only one FDA approved treatment (Fabrazyme) classified as an enzyme replacement therapy. However, approximately 88% of patients experience a severe immune response that, rarely, can be fatal and is a huge cost burden at average $250,000 a year per patient. The structure of α-galactosidase A has been previously determined to be a …

A Spectral Ct Method To Directly Estimate Basis Material Maps From Experimental Photon-Counting Data, Tal Gilat Schmidt, Rina Foygel Barber, Emil Y. Sidky

Biomedical Engineering Faculty Research and Publications

The proposed spectral CT method solves the constrained one-step spectral CT reconstruction (cOSSCIR) optimization problem to estimate basis material maps while modeling the nonlinear X-ray detection process and enforcing convex constraints on the basis map images. In order to apply the optimization-based reconstruction approach to experimental data, the presented method empirically estimates the effective energy-window spectra using a calibration procedure. The amplitudes of the estimated spectra were further optimized as part of the reconstruction process to reduce ring artifacts. A validation approach was developed to select constraint parameters. The proposed spectral CT method was evaluated through simulations and experiments with …