Biomedical Engineering and Bioengineering Commons^™

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Development Of A Long-Read Sequencing Protocol To Assess The Precision And Efficacy Of Gene Editing For Duchenne Muscular Dystrophy, Landon Andrew Burcham

Graduate Theses and Dissertations

This work establishes a method for assessing on-target precision due to CRISPR-Cas9 gene editing, especially within the context of exon skipping therapy for Duchenne Muscular Dystrophy. The proposed method utilizes an Oxford nanopore long-read sequencing approach to sequence amplified regions of DNA that have been edited using CRISPR-Cas9. NIH3T3 and C2C12 cell lines were treated with a dual-guide CRISPR-Cas9 system, that targets and deletes exon 23 from the DMD gene in mouse samples. Deletion PCR revealed deletion of exon 23 in both DNA and cDNA samples. Additionally, sequencing using Oxford Nanopore revealed targeted exon 23 deletion as the most prevalent …

Longitudinal Monitoring Of Tumor Response To Immune Checkpoint Inhibitors Using Diffuse Optical Spectroscopy, Joel Isaac Rodriguez Troncoso

Graduate Theses and Dissertations

Immune checkpoint drugs have completely changed the way people treat metastatic melanoma and non-small-cell lung cancer. While the impacts of these immunological checkpoints and their suppression on T cell function are well characterized, their consequences on the tumor microenvironment are not. In a CT26 mouse colorectal cancer model, we employed diffuse reflectance spectroscopy to track in vivo tumor microenvironmental alterations in response to immune checkpoint inhibitors. On three separate days, animals bearing CT26 tumor xenografts were given anti-PD-L1, anti-CTLA-4, a combination of both inhibitors, and isotype control. Within the first 6 days, monotherapy with either anti-PD-L1 or anti-CTLA-4 resulted in …

Investigating Effects Of Microenvironmental Stress On Cell Metabolism Using Multiphoton Imaging, Lisa Rebello

Graduate Theses and Dissertations

Resistance to therapy in cancer is a major cause of poor prognosis in patients. Tumor hypoxia plays an active role in mediating treatment resistance and has been linked to metastases and metastatic potential in cancer. Our research focused on three objectives: i) To understand metabolic effects of chronic and intermittent hypoxia in murine breast cancer cells and its affiliation with metastatic potential ii) To identify the metabolic changes associated with radiation therapy in a panel of radiosensitive and radioresistant human head and neck cancer cells and iii) to monitor the changes in cell metabolism associated with gain of treatment resistance. …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

In Vivo Metabolic And Vascular Response To Hypoxia In Twist Knockdown Murine Breast Cancer, Brandon Sturgill

Graduate Theses and Dissertations

Twist transcription factor is often overexpressed in aggressive tumors. Although needed in early embryonic development for organogenesis, Twist is known to induce an epithelial to mesenchymal transition in cells. In cancer, epithelial to mesenchymal transitions can lead to increased motility and invasiveness. It has also been linked to metabolic reprogramming and increased metastatic risk. Furthermore, metabolic preferences can increase proliferation, enhance metastatic potential, and influence the site of metastasis. We hypothesize that Twist directly affects the metabolism of cancer cells. We expect to see in vivo what we have seen in vitro; Twist overexpression should promote a shift away from …

Optimized Production And Evaluation Of Cellulose Nanocrystals Derived From Pre-Extracted Kraft Pulp Of Different Wood Species, Gurshagan Kandhola

Graduate Theses and Dissertations

Production of nanocellulose from a variety of naturally abundant, locally available and industrially significant wood species provides an opportunity for diversifying the portfolio of traditional pulp and paper industries. The U.S. has a prolific forest products industry with a well-established infrastructure that could be utilized for optimized and customized production of cellulose nanomaterials. However, to achieve that, it is important to a) understand how biorefining strategies for complete fractionation of biomass affect the downstream processing of pulp into nanocellulose, b) maximize the yields of cellulose nanocrystals and nanofibers (CNCs and CNFs) from pretreated raw materials, and c) evaluate if the …

Bioengineering Extracellular Matrix Scaffolds For Volumetric Muscle Loss, Kevin Roberts

Graduate Theses and Dissertations

Volumetric muscle loss overwhelms skeletal muscle’s ordinarily capable regenerative machinery, resulting in fibrosis and severe functional deficits which have defied clinical repair strategies. My work spans the design and preclinical evaluation of implants intended to drive the cell community of injured muscle toward a regenerative state, as well as the development of an understanding of the molecular responses of this cell community to biomaterial interventions. I demonstrate a new class of biomaterial by leveraging the productive capacity of sacrificial hollow fiber membrane cell culture; I show specifically that unique threads of whole extracellular matrix can be isolated by solvent degradation …

Diffuse Reflectance Spectroscopy To Quantify In Vivo Tissue Optical Properties: Applications In Human Epithelium And Subcutaneous Murine Colon Cancer, Gage Joseph Greening

Graduate Theses and Dissertations

Colorectal cancer is the 4th most common and 2nd deadliest cancer. Problems exist with predicting which patients will respond best to certain therapy regimens. Diffuse reflectance spectroscopy has been suggested as a candidate to optically monitor a patient’s early response to therapy and has been received favorably in experimentally managing other cancers such as breast and skin. In this dissertation, two diffuse reflectance spectroscopy probes were designed: one with a combined high-resolution microendoscopy modality, and one that was optimized for acquiring data from subcutaneous murine tumors. For both probes, percent errors for estimating tissue optical properties (reduced scattering coefficient and …

Impedance Sensing Of Cancer Cells Directly On Sensory Bioscaffolds Of Bioceramics Nanofibers, Hanan Alismail

Graduate Theses and Dissertations

Cancer cell research has been growing for decades. In the field of cancer pathology, there is an increasing and long-unmet need to develop a new technology for low-cost, rapid, sensitive, selective, label-free (i.e. direct), simple and reliable screening, diagnosis, and monitoring of live cancer and normal cells in same shape and size from the same anatomic region. For the first time on using an impedance signal, the breast cancer and normal cells have been thus screened, diagnosed and monitored on a smart bioscaffold of entangled nanowires of bioceramics titanate grown directly on the surface of implantable Ti-metal and characterized by …

Determining The Effect Of Locally Delivered Bioactive Modulators On Macrophage Activation At The Implantation Site Of Different Biomaterials In Rats, Kamel Alkhatib

Graduate Theses and Dissertations

Altering the foreign body reaction by targeting macrophages has been of interest in the biomaterials field to improve the integration of longevity of implanted biomedical devices. The objective of this dissertation was to study the effect of locally delivered bioactive modulators on macrophage activation at the implantation site of different biomaterials in rats. Iloprost, a prostacyclin analog, was tested for its ability to direct macrophages to their pro-wound healing phenotype after the implantation of microdialysis probe in the subcutaneous space of male Sprague Dawley rats. This study showed that iloprost can shift macrophage activation states in vivo to the pro-wound …

Mitochondrial Mrna Translation Is Required For Maintenance Of Oxidative Capacity, David Lee

Graduate Theses and Dissertations

Oxidative metabolism is required to produce adequate energy to sustain human life. A primary example of deteriorating oxidative capacity is seen in the cardiac musculature during chronic heart failure. This suggests that by improving oxidative potential, chronic heart disease could be mitigated and one approach to accomplish this may be through targeting the mt-mRNA translation system. Purpose: This investigation’s purpose was to characterize disruptions in mt-mRNA translation machinery in multiple forms of cardiomyopathy and to determine if mitochondrial mRNA translation initiation factor (mtIF2) is necessary to maintain oxidative capacity in cardiomyocytes. Methods Using a combination of animal and cell culture …

Intravenous Administration Of Iron Oxide Nanoparticles In The Chicken Model, Huong Thi Ngoc Le

Graduate Theses and Dissertations

To be used in health care, the safety and effectiveness of nanoparticles needs to be tested in a living organism. The objective of this project was to develop the chicken as a convenient animal model to examine tissue targeting of intravenously (i.v.)-injected iron oxide (IO) nanoparticles. In Experiment 1, different doses of IO-COOH were i.v. injected into chickens; blood was collected at 0, 5, 15, 30, and 60 minutes post-injection; liver, spleen, lung, and kidney were collected after the last blood collection. For Experiment 2, IO-COOH and IO-PEG were i.v. injected into chickens; blood and the organs were collected at …

Exploring The Production Of Extracellular Matrix By Astrocytes In Response To Mimetic Traumatic Brain Injury, Addison Walker

Graduate Theses and Dissertations

Following injury to the central nervous system, extracellular modulations are apparent at

the site of injury, often resulting in a glial scar. Astrocytes are mechanosensitive cells, which can create a neuroinhibitory extracellular environment in response to injury. The aim for this research was to gain a fundamental understanding of the affects a diffuse traumatic brain injury has on the astrocyte extracellular environment after injury. To accomplish this, a bioreactor culturing astrocytes in 3D constructs delivered 150G decelerations with 20% biaxial strain to mimic a traumatic brain injury. Experiments were designed to compare the potential effects of media type, number of …

Compounds Released From Biomass Deconstruction: Understanding Their Effect On Cellulose Enzyme Hydrolysis And Their Biological Activity, Angele Djioleu

Graduate Theses and Dissertations

The effect of compounds produced during biomass pretreatment on cellulolytic enzyme was investigated. Liquid prehydrolyzates were prepared by pretreating switchgrass using 24 combinations of temperature, time, and sulfuric acid concentration based on a full factorial design. Temperature was varied from 140°C to 180°C; time ranged from 10 to 40 min; and the sulfuric acid concentrations were 0.5% or 1% (v/v). Identified products in the prehydrolyzates included xylose, glucose, hydroxymethylfurfural (HMF), furfural, acetic acid, formic acid, and phenolic compounds at concentration ranging from 0 to 21.4 g/L. Pretreatment conditions significantly affected the concentrations of compounds detected in prehydrolyzates. When assayed in …

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Graduate Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important …

Impedance Biosensors For The Rapid Detection Of Viral And Bacterial Pathogens Using Avian Influenza Virus Subtypes H5n1 And H7n2 And Escherichia Coli O157:H7 As Model Targets, Jacob David Lum

Graduate Theses and Dissertations

This research investigated impedance biosensors for the rapid detection of viral and bacterial pathogens using avian influenza virus (AIV) subtypes H5N1 and H7N2 and Escherichia coli O157:H7 as the model targets, which were chosen due to their impact on the agricultural and food industries. For the detection of AIV H7N2, a single stranded DNA aptamer was selected using systematic evolution of ligands by exponential enrichment (SELEX). The selected aptamer and a previously selected aptamer against AIV H5N1 were used in a microfluidics chip with an embedded interdigitated array microelectrode to fabricate an impedance biosensor for specific detection of AIV H7N2 …

Electrospun Polycaprolactone Nanofiber Scaffolds For Tissue Engineering, Andreas Haukas

Graduate Theses and Dissertations

Stem cell and tissue engineering offer us with a unique opportunity to research and develop new therapies for treating various diseases that are otherwise incurable using traditional medicines. However, development of these new therapies replies upon the establishment of in vitro cell culture and differentiation systems that mimic in vivo microenvironments required for cell-cell and cell-ECM interaction. The development of these cell culture systems depends upon the identification of appropriate biomaterials and cell sources. Biomaterials should be carefully selected and fabricated into scaffolds for supporting cell growth and differentiation. In this study, we explored the fabrication of 3D electrospun nanofiber …