Biological Engineering Commons^™

Engineered Exosomes For The Multimodal Imaging Directed Photo-Immunotherapy Of Colorectal Cancer, Deepak S. Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Rio Grande Valley experience severe cancer health disparity. A novel therapeutic modality may serve as better therapeutic option. Nanohybrids endowed with multifunctionality, longer circulation time, large surface area have emerged as an active preference for cancer research. However, rising concern of nanomaterials toxicity and scalability issues has slowed their translation to clinics. Exosomes (Exo) are endogenous endocytic origin 40-100 nm vesicles found in various body fluids, which in comparison to synthetic nanoparticles, are biodegradable, highly biocompatible as well as immunocompatible in nature. Although bulk isolation of exosomes from human body fluids is still a problem and engineering of exosomes …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Photodynamic Therapy To Treat Triple Negative Breast Cancer In Vitro, Hunter S. Warren

All Theses

Triple negative breast cancer (TNBC) is the most resilient form of breast cancer, being one of the leading causes of death for women and making up 7% of all cancer deaths. Photodynamic therapy (PDT) offers a minimally invasive solution to TNBC as a passive-targeting treatment that reduces the need for other well established yet harsh treatments that can be taxing on the patient. PDT involves the use of a high-energy red light on the area of a tumor injected with photosensitizers (PS) that generate reactive oxygen species (ROS) in the tumor, triggering cell death. The PS tetra(hydroxyphenyl)chlorin (m-THPC) was used …

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park

McKelvey School of Engineering Theses & Dissertations

Gastrulation is an early morphogenetic process that is conserved across most metazoans and lays out the future body plan through the formation and shaping of the three germ layers: endoderm, mesoderm, and ectoderm. Despite its importance, not much is known about the events surrounding human gastrulation that occurs in utero due to ethical and technical limitations on studying human embryos. Therefore, many researchers have devised protocols for creating in vitro models of gastrulation using embryonic stem cells. Initially starting with mouse embryonic stem cells, the field of in vitro embryo models has advanced rapidly, with protocols using human embryonic stem …

Exploring The Effects Of Varied Land Use On Elemental Concentrations Within Streams, Logan Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

It is well documented that human activity influences the chemistry of surrounding waters. As such, it is possible that there is a link between land use within a watershed and the chemical composition of the stream. The objectives of this study are to determine if varied land use does affect the concentrations of macronutrients and trace elements present in the streams of Northwest Arkansas, and if so, to determine what extent urban and agricultural development are responsible for these changes. Water samples were collected across 19 streams in the Northwest Arkansas region between January and March of 2022. Water samples …

Breaks In Longitudinal Elastic Fibers Of Human Femoropopliteal Arteries, Elham Zamani

UNO Student Research and Creative Activity Fair

Breaks in Longitudinal Elastic Fibers of Human Femoropopliteal Arteries

Elham Zamani1, Majid Jadidi1

1 Department of Biomechanics, University of Nebraska Omaha, Omaha, NE

Introduction: Elastin is a major protein in the body with half-life >50 years. It is thought that elastic fibers are formed before the postnatal period. In the femoropopliteal artery (FPA), the main artery in the leg, longitudinal elastic fibers are present in External Elastic Lamina (EEL). Our team has studied more than 1000 cadaveric human FPA and has noticed that there are big breaks in their longitudinal elastic fibers in some subjects. Our goal in this work …

The Age-Dependent Characterization Of The Er-Alpha Positive Breast Cancer Tumor Microenvironment, Katie Marie Hamel

LSU Doctoral Dissertations

In disease states such as cancer, endocrine and paracrine signals from adipose tissue contribute to cancer progression and drug resistance. Young individuals diagnosed with estrogen receptor-alpha positive (ER-a+) breast cancer have an observed increase in resistance to endocrine therapies. This suggests that an alternative estrogen signaling pathway is active within these tumors. Despite this, the effects of stromal age on the endocrine response in breast cancer is not well known. Here, we review and highlight the involvement of the stromal age in both tumorigenesis and physiological wound healing. To identify specific differences between young and aged ER-a+ breast tumors, RNA …

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …

Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois

Doctoral Dissertations

Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …

Sonoporation-Mediated Loading Of Trehalose In Cells For Cryopreservation., Charles W. Shaffer Iv, David F. Grimm, Michael A. Menze, Jonathan A. Kopechek

Undergraduate Research Events

Trehalose, a non-reducing disaccharide, is present in many microorganisms and metazoans. In these organisms, trehalose acts as a stress protectant and helps preserve lipid membranes of cells during states of desiccation and freezing. Trehalose is required on both sides of the cell membrane to achieve a significant cryoprotective effect. Specific loading methods for trehalose are required since this sugar is impermeant to mammalian cells. Trehalose loading in mammalian cells has been achieved by fluid-phase endocytosis and genetic modification for the expression of trehalose transporters, however cryoprotective outcomes are unable to compete with established methods of cryopreservation for mammalian cells. Sonoporation …

Design Of A 3d Printed Bioreactor For Bone Cancer Research, Brooklyn K. Vanderwolde, Katelyn Hillson

The Journal of Undergraduate Research

Bone cancer is an aggressive disease and has peak occurrence during physiological stimulation of growth and aging. Astronauts who undergo long-term space missions also acquire an increased risk of bone tissue degeneration and cancer. Few in-vitro models currently exist capable of reproducing the complex microenvironment of bone tissue to support multicellular activity in a three-dimensional structure. This limits the ability to understand disease progression and develop suitable treatment strategies. Therefore, developing a bone tissue model and an associated bioreactor is critical to understand the risks associated with cancer progression and improve treatment and preventions related to those risks. The goal …

From Soap Bubbles To Cell Membranes, Peter Beltramo

Science and Engineering Saturday Seminars

Have you ever blown a soap bubble and wondered - what causes the bubble to be so stable and produces those colorful reflections of light? The answer lies in a class of molecules known as surfactants, and they have remarkable similarities with the molecules that comprise the cell membrane of all living organisms. In this workshop, we will use the analogy of a soap bubble to describe cellular membrane properties such as chemistry, structure, membrane transport, and ion channel formation. The goals of this workshop are to 1) link initially intractable concepts in biology like intracellular transport to the intuitive …

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline A. De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Epitaxially Grown Collagen Fibrils Reveal Diversity In Contact Guidance Behavior Among Cancer Cells, Juan Wang, Joseph W. Petefish, Andrew C. Hillier, Ian C. Schneider

Andrew C. Hillier

Invasion of cancer cells into the surrounding tissue is an important step during cancer progression and is driven by cell migration. Cell migration can be random, but often it is directed by various cues such as aligned fibers composed of extracellular matrix (ECM), a process called contact guidance. During contact guidance, aligned fibers bias migration along the long axis of the fibers. These aligned fibers of ECM are commonly composed of type I collagen, an abundant structural protein around tumors. In this paper, we epitaxially grew several different patterns of organized type I collagen on mica and compared the morphology …

Differentiation And Containment Of Derived Pancreatic Beta Cells, Caden Duffy, Alonzo Cook Ph.D.

Biomedical Engineering Western Regional Conference

Currently, the only permanent cure for Type 1 Diabetes is a pancreatic or islet transplant. With the shortage of donors, we are progressing research towards alternative therapies by differentiating induced pluripotent stem cells into derived pancreatic β-cells that can be transplanted and used as treatment for Type 1 Diabetes. We are investigating methods to increase the yield of fully derived, insulin producing pancreatic β-cells and are additionally researching the use of hydrophilized expanded polytetrafluoroethylene for use in cell containment devices. These devices could offer a future alternative for islet transplantation in human patients.

Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney

Doctoral Dissertations

To metastasize, a cell must travel through circulation to a secondary tissue, and this process causes 90% of all cancer deaths. Although inefficient, metastasis is not random, and only capable seeds in hospitable soils are capable of outgrowing into detectable metastases. The overall hypothesis in this work is that the secondary tissue microenvironment, particularly the extracellular matrix (ECM), mediates metastasis. We posit that the ability of metastatic cells to survive dormancy, exit quiescence, and colonize a tissue depends upon the ability of the soil to sustain survival, and subsequently trigger outgrowth. We created a simple biomaterial platform with systematic control …

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

The Role Of E-Cadherin Force In The Maintenance Of Homeostasis In Epithelial Acini, Fnu Vani Narayanan

Theses and Dissertations

Numerous three-dimensional model systems have emerged for emulating the biochemical and physiological states of native tissue. Yet little is known about the effects of mechanical forces on cell behavior in the context of an organized tissue structure in three-dimensional cell-culture. Epithelial cells cultured in a three-dimensional environment comprised of extracellular matrix proteins form spheroids of polarized cells. Cellular responses to mechanical cues, generated from dynamic interactions with the extracellular matrix and neighboring cells, are known to influence cellular behavior to a great extent. Previous studies have shown that tumorigenic progression has been frequently linked to the down regulation of E-cadherin, …

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 …

Three-Dimensional Confocal Microscopy Indentation Method For Hydrogel Elasticity Measurement, Donghee Lee, Md Mahmudur Rahman, You Zhou, Sangjin Ryu

Md Mahmudur Rahman

No abstract provided.

Terahertz Imaging Platform To Characterize The Growth Of In-Vitro Breast Tumors, Scarlett-Marie Acklin

Inquiry: The University of Arkansas Undergraduate Research Journal

This study aimed at evaluating the ideal plating method and density for imaging with the terahertz (THz) spectrometer. In this study, different methods were used to grow in-vitro tumors using the 4T1 cell line. Here, attempts to grow breast tumors in-vitro were conducted. Results were produced in two environments, flat-bottomed plates and round-bottomed multiwell plates. The second method allowed for faster clumping and increased cell aggregation, producing tumors up to 7mm. Terahertz spectroscopy produced images that correlated well to photomicrographs taken of the in-vitro tumors. This methodology shows great promise for providing a reliable, parameter-controlled source of in-vitro breast tumors …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Artificial Yeast Polarization Controlled By Chemical Gradient, James K. Nolan, Bernard Tao

The Summer Undergraduate Research Fellowship (SURF) Symposium

Engineering synthetic multicellular systems will lead to new synthetic biology technological platforms, inform developmental biology through recapitulation of natural systems and possibly unveil novel morphologies with practical applications not before reached throughout natural history (Maharbiz, 2012). Creating an exogenous molecular circuit that will polarize unicellular cells into “apical” and “basal” domains relative to a substrate plane would fulfill a missing component towards fully multicellular synthetic cellular communities (Maharbiz, 2012). To this end, a PIP₃ polarization network previously designed by Chau and associates (Chau, Walter, Gerardin, Tang, Lim 2012) was coupled to the specific activation by niacin of a recombinant …

Femtosecond Laser Patterned Templates And Imprinted Polymer Structures, Deepak Rajput

Doctoral Dissertations

Femtosecond laser machining is a direct-write lithography technique by which user-defined patterns are efficiently and rapidly generated at the surface or within the bulk of transparent materials. When femtosecond laser machining is performed with tightly focused amplified pulses in single-pulse mode, transparent substrates like fused silica can be surface patterned with high aspect ratio (>10:1) and deep (>10 μm) nanoholes. The main objective behind this dissertation is to develop single-pulse amplified femtosecond laser machining into a novel technique for the production of fused silica templates with user-defined patterns made of high aspect ratio nanoholes. The size of the …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …