Molecular, Cellular, and Tissue Engineering Commons^™

Investigating Endothelial Damage During Ischemic Stroke Treatment Using In Vitro And Computational Models, Zackary Lorton

Theses and Dissertations

Large vessel occlusion during acute ischemic strokes requires mechanical thrombectomy (MT) procedures using stent retrievers (SR). However, complete clot removal typically takes several attempts, which can amplify endothelial cell injury (EI). This project aims to characterize the extent of EI during MT using an in vitro vascular platform and a finite-element model (FEM). Impact of SR diameter and characterization of SR mechanical forces are assessed and correlated with human umbilical vein endothelial cell (HUVEC) response. HUVECs were seeded on fibronectin (4 µg/cm²) coated true-scale PDMS arterial phantoms with 2.5 mm luminal diameter. Test groups (n=6) either …

Novel Nucleus Pulposus Biomaterial Development And Low Field Mri Assessment For Intervertebral Disc Degeneration, Mario Krussig

All Dissertations

Intervertebral disc degeneration (IVDD) is a prominent pathology in the modern world that causes debilitating pain for many patients. The onset of IVDD occurs in the nucleus pulposus (NP). NP biomaterials will play a vital role in mitigating the progression of IVDD. Within this work, we sought to synthesize a solubilized extracellular matrix (ECM)-based NP biomaterial. Utilizing pepsin or urea extraction, bovine NP ECM was successfully solubilized (SBNPs). SBNP formulations were characterized biochemically, evaluated for cytotoxicity, and down-selected for front-running formulations. Leading candidate SBNPs were incorporated into an alginate bead biomaterial model to determine the potential bioactivity with human adipose-derived …

Low Impedance, Durable, Self-Adhesive Hydrogel Epidermal Electrodes For Electrophysiology Recording, Naiyan Wu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Traditional electrodes used for electrophysiology recording, characterized by their hard, dry, and inanimate nature, are fundamentally mismatched with the soft, moist, and bioactive characteristics of biological tissues, leading to suboptimal skin-electrode interfaces. Hydrogel materials, mirroring the high water content and biocompatibility of biological tissues, emerge as promising candidates for epidermal electronic materials due to their adjustable physicochemical properties. However, challenges such as inadequate electrical conductivity, elevated skin impedance, unreliable adhesion in moist conditions, and performance decline from dehydration have significantly restricted the efficacy and applicability of hydrogel-based electrodes. In this thesis, we report a high-performance hydrogel epidermal electrode patch for …

Review Of The Potential Use Of Poly (Lactic-Co-Glycolic Acid) As Scaffolds In Bone Tissue Recovery, Kushendarsyah Saptaji, Asriyanti Asriyanti, Nisa Khoiriyah, Laely Muryanti, Iwan Setiawan

Makara Journal of Science

Scaffolds are used as temporary tissue in the human body to expedite healing. Biocompatible materials play a vital role in the field of tissue engineering. Therefore, they can be used to reduce human pain as soon as possible. Polymeric materials are widely used to replicate bone tissue. Poly(lactic-co-glycolic acid) (PLGA) is a potential material for bone tissue scaffolds because of its superior properties, including compatibility with the human body. Accordingly, adding hydroxyapatite and introducing different fabrication methods can enable the production of PLGA scaffolds with good abilities to help cells grow, expand, differentiate, and proliferate. The paper reviews the current …

Development Of An In Vitro 3-Dimensional Co-Culture Human Colorectal Cancer Model In Microfluidic Devices, Abby Jens

Master's Theses

Colorectal cancer is the second most common cause of cancer-related deaths in the United States, with the relative 5-year survival rate for distant stage cancer being only 14%. The most common treatment for colorectal cancer is with chemotherapeutic drugs; however, the discovery of these drugs is costly, time-consuming, and often requires the use of animal models that do not yield results that translate to clinical trials. Due to these shortcomings, researchers seek to develop physiologically relevant in vitro tumor models that more accurately mimic the tumor microenvironment for cheaper and faster high-throughput drug screening. The aim of this research was …

Optimal Additive Fabrication Of Patient-Specific Bone Tissue Scaffolds Through Material Formulation, Computational Flow Simulation, And Material Deposition Monitoring, Ethan O’Malley

Theses, Dissertations and Capstones

The advancement of additive manufacturing technologies has opened new avenues for fabricating biocompatible and structurally functional bone tissue scaffolds, essential in treating osseous fractures, defects, and diseases. This research aims to develop mechanically strong, dimensionally precise, and patient-specific porous bone tissue scaffolds that provide both structural integrity and biological functionality. Through three interconnected studies, several key challenges in the fabrication of these structures using the PME additive manufacturing process are addressed. First, the influence of polysaccharide and hydroxyapatite concentrations on the compressive modulus of PME-printed porous scaffolds is investigated. By creating structures with varying hydroxyapatite and polysaccharide compositions, the study …

Numerical Design, Fabrication, And Characterization Of Porous Tissue Scaffolds For Bone Regeneration, Brandon Coburn

Theses, Dissertations and Capstones

With the recent advancements within biomedical engineering of bone tissue scaffolds, there is still a need to develop mechanically robust and biocompatible with low immunogenicity for bone regeneration. Additionally, the evaluation of the fluid dynamics of the porous Triply Periodic Minimal Surfaces (TPMS) bone scaffold also shows the need for investigation due to the complex fluid interaction of hemodynamics that occurs with the scaffold internal and external domains. To aid in the development of treating bone fractures, defects, and diseases. Furthermore, with the induction of a wide variety of TPMS architecture that yields different topologies, the Convolutional Neural Network (CNN) …

Long-Term Simulation Of Stem Cell Mechanobiology, Manoochehr Rabiei

Mechanical and Aerospace Engineering Dissertations - Archive

An accurate representation of cellular mechanobiology necessitates the inclusion of subcellular elements characterized by minute masses and dimensions. These minute objects yield multiscale dynamic models with disproportionate terms, which require inordinate amounts of computational time to simulate. The computational requirements limit the time span of the simulation to time histories shorter than one second, even when employing supercomputers. This work presents a high-speed approach to simulating the mechanobiology of stem cells. The proposed approach separates the computational time from the size, and distribution, of masses of the subcellular elements, enabling the simulation of weeks-long cellular processes within hours on a …

Dihydroethidium-Derived Fluorescence In Electrically Stressed Cells Indicates Intracellular Microenvironment Modifications Independent Of Ros, Esin B. Sözer, Iurii Semenov, P. Thomas Vernier

Bioelectrics Publications

Intracellular reactive oxygen species (ROS) generation is widely suggested as a trigger for biological consequences of electric field exposures, such as those in electroporation applications. ROS are linked with membrane barrier function degradation, genetic damage, and complex events like immunological cell death. Dihydroethidium (DHE) is commonly used to monitor ROS in cells. DHE is linked to intracellular ROS by a primary oxidation product, Ethidium (Eth⁺), that shows increased fluorescence upon binding to polynucleotides. We observed changes in DHE-derived fluorescence in Chinese hamster ovary (CHO) cells post 300-ns electric pulse exposures, comparing them to tert-butyl-hydroperoxide (t-BHP) induced oxidative stress. …

Quantification Of Antiviral Drug Tenofovir (Tfv) By Surface-Enhanced Raman Spectroscopy (Sers) Using Cumulative Distribution Functions (Cdfs), Marguerite R. Butler, Jana Hrncirova, Meredith Clark, Sucharita Dutta, John B. Cooper

Chemistry & Biochemistry Faculty Publications

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive spectroscopic technique that generates signal-enhanced fingerprint vibrational spectra of small molecules. However, without rigorous control of SERS substrate active sites, geometry, surface area, or surface functionality, SERS is notoriously irreproducible, complicating the consistent quantitative analysis of small molecules. While evaporatively prepared samples yield significant SERS enhancement resulting in lower detection limits, the distribution of these enhancements along the SERS surface is inherently stochastic. Acquiring spatially resolved SERS spectra of these dried surfaces, we have shown that this enhancement is governed by a power law as a function of analyte concentration. Consequently, by definition, …

Investigating The Regulation Of Epithelial-Mesenchymal Transition Through Fibronectin-Mediated Tgf-Β1 Mechanotransduction Using In Vitro Models Of Triple-Negative Breast Cancer, Michael M. Sofroniou

Theses and Dissertations

TGF-β1 is a potent regulator of epithelial-mesenchymal transtion (EMT), a cellular
transdifferentation process that promotes cellular motility and matrix remodeling, critical to tumorigenesis and metastasis. TGF-β1-induced EMT promotes the assembly of FN, which synergistically binds latent TGF-β1 to aid in its activation. The purpose of of this work is to further probe the effects of autocrine TGF-β1 signaling during EMT progression by utilizing CRISPR-Cas9 deletion of the TGFB1 gene in in vitro models of triple-negative breast cancer. The studies outlined in this work demonstrate that autocrine TGF-β1 maintains a baseline level of mesenchymal marker expression. It also functions to desensitize …

The Effect Of Phase-Separated Microstructures On Cell Migration In 3d Dextran Hydrogels, Jenifer Sidhwa

Honors Theses and Capstones

No abstract provided.

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

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, …

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.

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 …

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 …

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 …

The Sexually Dimorphic Role Of Connexin 43 In Bone Remodeling And Disuse-Induced Bone Loss, Gabriel A. Hoppock

Theses and Dissertations

Bone loss is frequently experienced by individuals undergoing long-term disuse, such as prolonged bedrest, immobilization due to paralysis or injury, and conditions such as spaceflight. Under normal physiological conditions, bone remodeling is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts, and the activity of osteoblasts and osteoclasts is orchestrated by osteocytes. Osteocytes are the most abundant cell type found in bone and ample evidence suggests they are bone’s main mechanosensory cell type. Therefore, understanding osteocyte biology and responses to mechanical signals, or lack thereof during unloading, may lead to new therapeutic targets to combat bone loss during disuse. Previous data has …

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 …

Muscle-Nerve Signaling And Its Role In Myogenesis, Synaptogenesis, And Regeneration, James T. Redden

Theses and Dissertations

Despite only comprising 0.1% of the myofiber surface area, a healthy motor endplate is densely packed with acetylcholine receptors (AChRs) responsible for mediating activity between the connected motor neuron and skeletal muscle via the neurotransmitter, acetylcholine. Loss of the endplate, known as fragmentation, is caused by car crashes, deep lacerations, and other traumatic injuries to the innervating nerve or direct injuries to the limb muscle(s) with intramuscular denervation as a common comorbidity. In both cases, endplate fragmentation begins within a week of injury proceeding muscle atrophy causing decreased mobility, paralysis, and quality of life. Endplate fragmentation of intact muscle fibers …

T Cell Polarization Regulates The Inflammatory Response And Tissue Regeneration At The Peri-Implant Interface, Derek Avery

Theses and Dissertations

Unresolved healing and localized chronic inflammation are common occurrences after biomaterial implantation, resulting in unfavorable clinical outcomes such as implant failure or fibrous encapsulation. T cells are adaptive immune cells found in lymph nodes, thymus, spleen, bone marrow, and around biomaterials, significantly impacting the degree of inflammation and wound healing. T cells are vital for inflammatory cytokine production and modulation of innate immune cells, including neutrophils and macrophages. T cells can be differentiated into two primary subsets, CD4⁺ and CD8⁺ T cells, playing distinctive roles in various pathologies and disease states. While T cells have been characterized well …

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 …

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 …

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 …

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 …

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 …