Molecular, Cellular, and Tissue Engineering Commons^™

Matrix Stiffness Sensing By Nascent Adhesions And The Role Of Riam In Adhesion Assembly, Nikhil Mittal

Dissertations, Master's Theses and Master's Reports

Mechanical stiffness of the extracellular matrix (ECM) impacts many cellular functions such as proliferation, migration, and differentiation. ECM stiffness is sensed by a cell via integrin-based focal adhesions (FAs) by changing conformation and biochemical activities of molecules within FAs by the exchange of the force between the ECM and filamentous actin (F-actin). Cells in turn respond to this stiffness by generating traction force that plays an important role in many biological events such as tissue morphogenesis, stem cell differentiation, wound healing, and cancer cell metastasis. The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions. Understanding stiffness sensing …

Cellular Level Changes Induced In Cancer Cells Due To Microgravity, Sai Deepika Reddy Yaram

Graduate Theses, Dissertations, and Problem Reports (ETD)

The increase in human activity in space has revealed several kinds of physiological challenges brought on by the absence of Earth's gravitational pull. NASA observed that during spaceflight, astronauts experience a 1-1.5% monthly loss in the mineral density of weight-bearing bones, with rehabilitation efforts on Earth often proving ineffective. This issue extends to muscles, the neuro vestibular system, the cardiovascular system, and vision. Cancer has emerged as a significant cause of mortality among astronauts, with studies up to 2017 showing that 41.3% of natural cause deaths among U.S. astronauts were due to cancer, primarily due to space radiation exposure. Cancer …

4d Epr Oximetry Imaging For 4d Bioprinting And Tissue Engineering, Sajad Sarvari

Graduate Theses, Dissertations, and Problem Reports (ETD)

Bioprinting, akin to 3D printing, employs cell-laden hydrogels such as GelMA (Gelatine Methacrylate) and Alginate instead of plastic or resin to create biological structures. The printing process followed by subsequent tissue maturation is known as 4D bioprinting, where the fourth dimension is time. Ensuring adequate and consistent oxygen, O2, supply within 3D bioprint volume over the entire maturation period process is crucial, as even transient hypoxia can impact cellular behavior and phenotypes. However, printing of fully developed vasculature remains an unresolved technical challenge. Several approaches to chemically (peroxides) or biologically (photosynthesis) generate oxygen during bioprint maturation have been proposed. However, …

The Effects Of Various Nanoplastics On The Inflammatory Response In Primary Alveolar Epithelial Cells, Eunice J. Pak

Theses and Dissertations

As plastic pollution begins to multiply in the environment and the workplace, gradual degradation of these plastics creates an unseen threat to biological health: nanoplastics. These nanoplastics are common in day-to-day life, and have been found in various internal organs of the human body. The biological and health effects of these nanoplastics are still widely unknown, and only recently has research focused on the impacts of these particles on human health at the cellular level.

In this thesis, poly(methyl methacrylate) and three forms of polystyrene (carboxyl-modified, amine-modified, and neutral surface charge) have been tested on submerged primary C57BL/6 mouse alveolar …

The Regulation Of Laryngeal Cancer Cell Phenotype And Proliferation By 24r,25-Dihydroxyvitamin D3 Is Correlated With Erα Isoform Expression, Cydney Dennis

Theses and Dissertations

Laryngeal cancer is the most common type of head and neck cancer and is associated with poor prognosis due to common delayed diagnoses. The sex disparities associated with laryngeal cancer are constantly growing, as the risk of malignancy in males is continually increasing compared to women. Due to the high chance of late-stage diagnosis requiring aggressive treatments, there is a high demand for less aggressive treatment options and early-stage diagnostic markers. The apparent sex disposition of the larynx, the correlation between sex hormones, and the risk of malignancy in aging men suggest that estrogen may play a role in laryngeal …

A 3d Co-Culture Model Of Senescent Cell Burden And Salivary Gland Fibrosis, Stephen Rose

Electronic Theses & Dissertations (2024 - present)

Patients with head and neck cancer often suffer collateral radiation damage to the salivary glands, leading to fibrosis. Histological examinations indicate that radiation encourages fibrosis by promoting cellular changes leading to both senescent and myofibroblast phenotypes, coupled with a significant loss of regenerative and acinar cells. Chronic hypofunction remains a primary concern, even with modified radiation approaches to sparing salivary glands. Current treatments primarily offer symptomatic relief without rectifying irreversible glandular tissue damage. This limitation arises, in part, from a deficiency in predictive preclinical models to study this multifaceted problem.

We introduce a 3D in vitro microtissue model to address …

Wavelet-Based Harmonization Of Local And Global Model Shifts In Federated Learning For Histopathological Images, W. Farzana, A. Temtam, K. M. Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Federated Learning (FL) is a promising machine learning approach for development of data-driven global model using collaborative local models across multiple local institutions. However, the heterogeneity of medical imaging data is one of the challenges within FL. This heterogeneity is caused by the variation in imaging scanner protocols across institutions, which may result in weight shift among local models leading to deterioration in predictive accuracy of global model. The prevailing approaches involve applying different FL averaging techniques to enhance the performance of the global model, ignoring the distinct imaging features of the local domain. In this work, we address both …

Investigation Of The Effect Of Preparation Parameters On The Structural And Mechanical Properties Of Gelatin/Elastin/Sodium Hyaluronate Scaffolds Fabricated By The Combined Foaming And Freeze-Drying Techniques, Mansour Qamash, S. Misagh Imani, Meisam Omidi, Ciara Glancy, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

This paper aimed to evaluate the effects of different preparation parameters, including agitation speed, agitation time, and chilling temperature, on the structural and mechanical properties of a novel gelatin/elastin/sodium hyaluronate tissue engineering scaffold, recently developed by our research group. Fabricated using a combination of foaming and freeze-drying techniques, the scaffolds were assessed to understand how these parameters influence their morphology, internal microstructure, porosity, mechanical properties, and degradation behavior. The fabrication process used in this study involved preparing a homogeneous aqueous solution containing 8% gelatin, 2% elastin, and 0.5% sodium hyaluronate (w/v), which was then subjected to mechanical agitation at speeds …

Polarizable Amoeba Force Field Predicts Thin And Dense Hydration Layer Around Monosaccharides, Luke A. Newman, Mackenzie G. Patton, Breyanna A. Rodriguez, Ethan W. Summer, Valerie Vaissier Welbourn

Chemistry & Biochemistry Faculty Publications

Polarizable force fields crucially enhance the modeling of macromolecules in polar media. Here, we present new parameters to model six common monosaccharides with the polarizable AMOEBA force field. These parameters yield a thinner, but denser, hydration layer than that previously reported. This denser hydration layer results in eliminating non-physical aggregation of glucose in water-an issue that has plagued molecular dynamics simulations of carbohydrates for decades.

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Design, Development, And Validation Of A Perfusion-Compression Bioreactor To Study Osteogenesis In Bone Explants, Alexis Victoria Graham

Theses and Dissertations

The current gold standard treatment for bone defects is autologous cancellous bone graft, which involves increased surgery time and donor site morbidity, and limited supply of bone and cells for regeneration. Bioreactors may aid in the generation of mechanically conditioned bone grafts with more cells compared to traditional grafts. However, the specific parameters of fluid flow and mechanical loading which contribute to osteogenesis and cell viability in bioreactors are not fully characterized. Here, a perfusion-compression bioreactor system was developed to study osteogenesis in porcine trabecular bone explants. Loading accuracy was over 88% across six bioreactors at a 0.1 s-1 strain …

Experimental And Computational Platforms For Studying Systems Mechanobiology, Brendyn Miller

All Dissertations

Mechanical stimulation through physical activity has been shown to play an important role in treating and preventing several non-communicable diseases such as hypertension, lower back pain (LBP), type-2 diabetes mellitus, and several cancers. This is accomplished through the regulation of cellular behavior and tissue remodeling within the body at both the micro- and macro-scale levels. The goal of mechanobiology research is to gain in-depth knowledge and understanding of how cells sense physical forces in conjunction with other biochemical cues and translate those factors into important biological functions that either maintain tissue homeostasis or lead to pathological states. Understanding these processes …

Design Of Human Serum Albumin And Adenovirus Conjugation Via Catcher/Tag Molecular Glue, Peijie Zhao

McKelvey School of Engineering Graduate Student Theses & Dissertations

Adenovirus (Ad) has been the ideal cargo delivery mechanism, and its moderate immunological response makes it ideal for in vivo gene therapies since its discovery in 1953. However, the robust immunogenicity of the Ad capsid and low vaccine absorption via mucous membranes and epithelium put a limit on the process of developing intranasal vaccines. Efforts are being made to enhance the effectiveness of Ad vectors and numerous studies have demonstrated the remarkable capacity of human serum albumin (HSA) to extend plasma half-life and facilitate targeted intranasal delivery. In this study, we devised an innovative method for employing the Catcher/Tag molecular …

An In Vitro Platform To Characterize Myocardial Wound Remodeling, Jonathan Heywood

All Dissertations

Heart Failure, sometimes called Congestive Heart Failure, is a collection of pathological disruptions in which the heart is unable to pump blood properly. It affects over 6 million people in the United States, with the cost-per-patient at approximately $30,000 and the total cost estimated to be $160 billion by 2030. There is no single cause of heart failure, as it can manifest as a varying array of diseases, disorders, and syndromes. However, many of these underlying diseases result specifically from dysregulation of mechanically active cells called cardiac fibroblasts, which play a critical role in the remodeling of the extracellular matrix …

Tissue-Engineered Models For Investigating Nerve Infiltration In Fibrotic Microenvironments, Nikolas Ala-Kokko

Graduate Theses and Dissertations

Neuron infiltration is involved in a multitude of diseased states and is critical in the regeneration of physiologic conditions. Modeling of innervation in three-dimensional, heterogenous, environments would allow early investigation in the crosstalk of neurons and native cells in normal and pathophysiologic microenvironments to gain an understanding of mechanistic functions. This would allow for greater insight into the role of metabolism, cell adhesion, microenvironmental alternations, cellular crosstalk, and signaling pathways that play a role in the promotion and prevention of neurite growth. In this thesis, with the construction of collagen-based hydrogels as the foundation for cell culture, we investigate cell …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

All Dissertations

Cardiovascular diseases are the leading cause of death worldwide. Heart disease, in particular, accounted for 1 in every 5 deaths in the United States in 2021, representing a substantial public health burden that will require more effective treatment options to alleviate. Heart transplant surgery is currently the only option to completely restore cardiac function, but many patients die while waiting for a transplant due to a longstanding organ donor shortage. Thus, there is a dire need for accessible treatment options that can repair damaged hearts. Recent advances in tissue engineering and regenerative medicine have accelerated the development of therapies for …

Integrative Transcriptomics And Proteomics Profiling Of Arabidopsis Thaliana Elucidates Novel Mechanisms Underlying Spaceflight Adaptation, Gbolaga O. Olanrewaju, Natasha J. Haveman, Michael J. Naldrett, Anna-Lisa Paul, Robert J. Ferl, Sarah E. Wyatt

Nebraska Center for Biotechnology: Faculty and Staff Publications

Spaceflight presents a unique environment with complex stressors, including microgravity and radiation, that can influence plant physiology at molecular levels. Combining transcriptomics and proteomics approaches, this research gives insights into the coordination of transcriptome and proteome in Arabidopsis’ molecular and physiological responses to Spaceflight environmental stress. Arabidopsis seedlings were germinated and grown in microgravity (μg) aboard the International Space Station (ISS) in NASA Biological Research in Canisters – Light Emitting Diode (BRIC LED) hardware, with the ground control established on Earth. At 10 days old, seedlings were frozen in RNA-later and returned to Earth. RNA-seq transcriptomics and TMTlabeled LC-MS/MS proteomic …

Computational Modeling Using A Novel Continuum Approach Coupled With Pathway-Informed Neural Networks To Optimize Dynein-Mediated Centrosome Positioning In Polarized Cells, Arkaprovo Ghosal, Padmanabhan Seshaiyar Dr., Adriana Dawes Dr., General Genomics Inc.

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Development Of An Angiogenic Tissue-On-A-Chip Microenvironment, Eric Stuehr

Master's Theses

Preclinical testing is necessary to investigate the safety and efficacy of novel therapeutics before moving to clinical trials, yet approximately 90% of these therapies fail once tested in humans. This has led to increased interest in developing robust preclinical models that accurately mimic the complex human in vivo physiology. Microfluidic devices that can introduce dynamic conditions to 3D cell/organoid cultures, also known as tissue-on-a-chip, have emerged as physiologically relevant in vitro preclinical models that can achieve high throughput screening of therapeutics. The research presented here aimed to develop an angiogenic environment within a novel microfluidic device to stimulate formation of …

Characterization Of Influenza-Specific Antibodies, Xinping Ran

ENGS 86 Independent Projects (AB Students)

Influenza viruses cause respiratory illness that affects 8% of the U.S. population annually. However, current influenza vaccines have a limited efficacy of only 40-60%. This highlights the need for a universal vaccine design that can generate broadly neutralizing antibodies against influenza surface protein hemagglutinin (HA). Previous work by our group identified HA-specific monoclonal antibodies (mAbs) from serum samples through high-throughput antibody profiling. In this study, three of the identified mAbs were generated using mammalian cell expression and their binding affinity against three HA antigens was characterized via Enzyme-Linked Immuno-Sorbent Assay (ELISA). The ELISA results demonstrated specific binding affinity towards B/Yamagata/18/1998 …