Biological Engineering Commons^™

A Computational Micropatterning Approach To Study Caveolae And Protein Localization In Vascular Biology, Andrew B. Grespin

Electronic Theses and Dissertations

Caveolae are specialized, flask-shaped membrane invaginations highly expressed in endothelium and dysregulated in atherosclerosis. Caveolae play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. Thus, we sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. However, cell culturing, the backbone of human-focused biological research, does not standardly do well to model physiologically relevant cell behaviors such as migration or polarity-based tissue formation, particularly for punctate proteins and structures like caveolae. Micropatterns are cell-adhesive shapes that biophysically confine cell(s) to a user defined geometry which stereotype organelle …

Strategic Enhancement Of Biofuel Production Using Bacillus Subtilis As A Model Organism: A Dual Approach Of Gene Essentiality Mapping And Optimization, Angela A. Zebede

Electronic Theses and Dissertations

With rising global demand for renewable energy, enhancing microbial platforms for biofuel production is vital. This study engineered Bacillus subtilis to improve resilience to solvent stress by targeting membrane lipid biosynthesis pathways essential for integrity. Growth curve analysis (OD₆₀₀) showed that phosphatidylserine (PS) and phosphatidylethanolamine (PE) knockout strains grew significantly slower than wild type (168), indicating the importance of these lipids under stress. Laurdan fluorescence spectroscopy was used to assess membrane properties. Generalized polarization (GP) analysis revealed a concentration-dependent reduction in membrane order upon 1%–2% 1-butanol exposure. GP values declined progressively from control to 2% treatment, reflecting increased membrane fluidity …

Reproducibility In Modeling Of Knee Joint Mechanics, Maryam Nazem

Electronic Theses and Dissertations

Computational modeling of knee joint biomechanics can provide valuable insights into joint function, injury mechanisms, and patient outcomes, and can support surgical planning and informed clinical decision-making. However, achieving consistent and repeatable results, or reproducibility, is a significant challenge that affects the credibility of these models. This thesis addresses reproducibility through two studies related to the KneeHub Project, which is a multi-institutional collaboration designed to investigate reproducibility in finite-element modeling of the knee.

The first study involved model benchmarking, where predicted results of the calibrated models were compared with the experimental data to evaluate model reproducibility. While all models replicated …

Influence Of Obesity On Knee Joint Mechanics: A Subject-Specific Musculoskeletal Modeling Approach, Ryan C. Knowles

Electronic Theses and Dissertations

Obesity has been consistently linked to knee osteoarthritis (KOA), a debilitating joint disease. While prior work has shown that obese individuals often walk with altered biomechanics compared to normal-weight (NW) individuals, which may accelerate KOA progression, less is known about how these mechanics affect load distribution between the medial and lateral tibiofemoral (TF) compartments, particularly during higher-demand activities. This study developed subject-specific musculoskeletal models of five obese and five NW individuals, incorporating CT-based bone measurements and individualized joint contact points. Simulations were driven by six degree-of-freedom (6DOF) kinematics obtained from high-speed stereo radiography (HSSR) to predict TF loading and associated …

Computational Fluid Dynamics And Fluid Structure Interaction Modeling In Healthy Vertebral Arteries: A Comparative Study, Bryce Clinkenbeard

Electronic Theses and Dissertations

Cerebral perfusion is critical for maintaining proper brain function, with each cerebrovascular artery playing an integral role in the overall cerebrovascular system. When these arteries become damaged or develop plaque, cardiovascular disease (CVDs) such as atherosclerosis can arise, leading to conditions like arterial stenosis. While CVDs are most prevalent in older individuals, they are also observed in young adults, particularly those engaged in high-endurance occupations such as military service. Diagnosis and prediction of CVDs often rely on imaging modalities supported by computational fluid dynamics (CFD) which account for low resolution in fluid flow. CFD models assume rigid arterial walls, which …

Alterations And Improvements Of The Photoacoustic Flow Cytometry Method, Nicholas J. Taylor

Electronic Theses and Dissertations

The emergence and proliferation of antibiotic-resistant bacteria present a significant and growing challenge to global public health, with the potential to render many existing antibiotics ineffective. Infections caused by these resistant pathogens are difficult to treat, resulting in higher morbidity, mortality, and healthcare costs. A major obstacle in combating these infections is the slow pace of traditional diagnostic methods, such as blood cultures, which typically take 2-3 days to identify the causative bacteria and determine their antibiotic resistance profiles. This delay in diagnosis hinders timely interventions and appropriate treatment, further contributing to the spread of resistant infections. As such, there …

The Impact Of Cumulative And Acute Loading On Achilles Tendon Health, Performance, And Reported Pain In Collegiate Gymnasts, Julio Serrano Samayoa

Electronic Theses and Dissertations

Gymnasts are at a high risk of Achilles tendon (AT) injuries due to intense loads during takeoffs and landings. To better understand better the relationship between impact loading and its effects on tendon adaptation and athletic performance, this study uses Inertial Measurement Units (IMUs) to track AT loading across a collegiate gymnastics season. This data were compared against physiological and athletic performance metrics, obtained through force plates and ultrasound imaging, to explore how mechanical load influences reported pain and athletic performance. Results varied, with cumulative impacts being correlated with improved jump height (Spearman 0.362, Pearson 0.348), while peak power and …

Statistical Modeling Of Knee Morphology And Material Properties Considering Diverse Populations, Gabrielle Jeannine Kindy

Electronic Theses and Dissertations

Total Knee Arthroplasty (TKA) is a widely performed surgical procedure aimed at alleviating pain and restoring function in patients with severe knee osteoarthritis. Despite its general success, disparities in postoperative outcomes have been observed across different racial and ethnic groups, with minority populations often experiencing less favorable results. One potential avenue for improving the generalizability of orthopaedic implants is using Statistical Shape and Intensity Models (SSIMs), which can be used to incorporate patient variability directly into the orthopaedic medical device development workflow through population-based finite element analysis.

This work aimed to construct an SSIM from a diverse subject set, incorporating …

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 …

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 …

Labeling Melanoma Cells With Black Microspheres For Improved Sensitivity In Detection Via Photoacoustic Flow Cytometry, Tori Kocsis

Electronic Theses and Dissertations

Melanoma is an aggressive form of skin cancer known for developing into metastatic disease. Current clinical diagnostics, including medical imaging and tissue biopsy, provide a poor prognosis since the cancer is in the late stages of disease progression. In recent years, photoacoustic flow cytometry has allowed for the detection of circulating melanoma cells within patient blood samples in vitro. Although this method exploits the naturally-produced melanin within the cells, it has only successfully detected highly-pigmented melanoma cell lines. Since various forms of melanoma exist, each with varying melanin concentrations, this research aims to provide a novel method for detecting lightly-pigmented …

Aerodynamics And Turbulent Wake-Flow Characteristics Of Owls During Flapping Flight, Krishnamoorthy Krishnan

Electronic Theses and Dissertations

Owls exhibit unique flight capabilities in the low Reynolds number flow regime which is prone to complex viscous flow phenomena. They possess unique feather features and flexible wing structures which are postulated to help them fly nearly silently and stably at low speeds in a complex flow setting. Understanding the aerodynamics of owls could pave the way to enhance the future designs of small flying vehicles. Though it has been a focus of research over multiple decades, no conclusive agreement has been attained on the aerodynamic mechanisms associated with owl flight. Particularly, the aerodynamics of flapping owl flight is severely …

Investigating The Effect Of Dissolved Oxygen-Assisted Corneal Cross-Linking (Cxl) On Porcine Corneas, Julianni Dar

Electronic Theses and Dissertations

Corneal cross-linking is a clinical procedure that is known to stop the progression of keratoconus, an eye disease that affects the cornea’s structure, ultimately leading to vision loss in its advanced stages. The typical treatment plan includes riboflavin and UV-A exposure in the hope to increase the mechanical properties of the cornea. There are two types of CXL pathways, with Type-II CXL requiring oxygen. Naturally, the dissolved oxygen is limited in the cornea; therefore, limiting the effect of Type-II CXL. This study proposes to improve the Type-II CXL contribution by integrating dissolved oxygen during the standard CXL treatment used in …

Fabrication And Characterization Of Lactobacillus Crispatus Containing Bioprints For Bacterial Vaginosis Application., Anthony J. Kyser

Electronic Theses and Dissertations

Bacterial vaginosis (BV) is a condition in which healthy lactobacilli are replaced by an overabundance of pathogenic bacteria in the female reproductive tract. Current antibiotic treatments often fail to “cure” infection, resulting in recurrence in more than 50% of women, 6 months post-treatment. Recently, probiotics have demonstrated promise to restore vaginal health; however, as with other active agents, delivery requires once-to-twice daily administration. Recently, three-dimensional (3D)-bioprinting has enabled the fabrication of well-defined cell-laden architectures with tunable agent release, thereby presenting a novel approach with which to deliver probiotics. One promising bioink, gelatin alginate, was selected for study, due to its …

Improving Quantification Of Mitral Regurgitation Through Computational Fluid Dynamics And Ex Vivo Testing, Alexandra Flowers

Electronic Theses and Dissertations

Mitral regurgitation (MR) is a prominent cardiac disease affecting more than two million people in the United States alone. In order for patients to receive proper therapy, regurgitant volume must first be quantified. As there are an array of methods to do so, the proximal isovelocity surface area (PISA) method continues to be the most accurate and clinically used method. However, there are some difficulties obtaining the necessary measurements need for this when performing transthoracic echocardiography. This study aims to evaluate and present techniques that may be used to more accurately quantify regurgitation through ex vivo testing and computational fluid …

Pulmonary Valve Replacement, Mina Shafiei

Electronic Theses and Dissertations

Currently, transcatheter pulmonary valve replacement (TPVR) is a well-established alternative for surgical pulmonary valve replacement (SPVR) to treat pulmonary valve disorders in patients with prior congenital heart surgery. Edwards Sapien 3 valve is a bioprosthesis originally designed for the aortic position but has been used off-label in native right ventricular outflow tract (RVOT). It is currently under clinical trial to get food and drug administration (FDA) approval.

This study is a comparison of the performance of Sapien 3 with surgical bioprosthetics. The in vitro tests result showed Sapien 3 experiences less degree of opening and effective orifice area in pulmonic …

Revision Total Hip Femoral Stem Micromotion And Statistical Shape Modeling Of The Knee, William Fugit

Electronic Theses and Dissertations

The first purpose of this thesis was to compare the amount of micromotion seen in the femoral stem in a revision total hip arthroplasty between simple loading conditions and loading conditions derived from activities of daily living, through the use of experimental and computational methods. The amount of micromotion at the bone-implant interface was larger for activities of daily living, with ranges of 200μm more than the largest simple loading conditions. The second purpose of this thesis was to compare measurements of accuracy in a statistical shape model between individual bone and joint-level models, specifically for the knee. Using computational …

Real-Time Monitoring Of Cell Death Progress Using Capacitance Spectroscopy, Suyang Wu

Electronic Theses and Dissertations

Biologics, including the monoclonal antibody (mAb), has experienced rapid development in the last decade. However, the price of biologics is often prohibitively high because of the low process efficiency. Delaying the inevitable cell death improves the productivity of upstream bioprocessing, whose success relies on monitoring the cell death onset that indicates the timing for preventive actions.

This study proposes to develop a real-time monitoring model that quantifies the dying cell percentage in lab-scale bioreactors using capacitance spectroscopy. The capacitance spectroscopy contains cell death-related information due to various physical properties changes during the cell death process, e.g., cytoplasmic conductivity change. The …

Correlating With Local Variation In Collagen Level And Mechanical Properties Of The Heart Tissues, Talayeh Tavangar

Electronic Theses and Dissertations

The determination of the myocardium's tissue properties is essential in constructing finite element (FE) models of the heart. To obtain accurate results, especially for functionally modeling the heart, we must determine the tissue properties in-vivo. The calculation of the heart tissue properties remains a challenging area as it is categorized as a heterogeneous, anisotropic, nonlinear soft tissue that undergoes large deformation. In this work, we tried to introduce and evaluated a finite element method to determine the mechanical properties of the cardiac tissue. The introduced method combined a finite element modeling with the experimentally obtained images from the left and …

Tibial Strains And Tray-Bone Micromotions After Total Knee Arthroplasty: Computational Studies Evaluating The Tibial Fixation, Huizhou Yang

Electronic Theses and Dissertations

Cemented and cementless fixation in total knee arthroplasty (TKA) have been successfully used for decades. As the number of younger and more active patients treated with TKA continues to increase, long-term implant survivorship is of increasing importance. One of the most common complications and hence the reason for revision is mechanical loosening (23.1% of all revised TKA). The loosening mechanisms have been proposed for different fixation types. For cemented fixation, bone remodeling after surgery is regulated by the changes in strain energy density (SED). The recruitment of osteoclasts and osteoblasts is controlled by SED-related signals. Insufficient stimuli can promote bone …

Bacteria Analysis By Using A Supervised Machine Learning Algorithm Based On Droplet Microfluidics, Yulder Daniel Angarita

Electronic Theses and Dissertations

Sepsis is a major medical problem and massive resources have been invested in developing and evaluating alternative treatments. Statistics indicate that sepsis causes between one third and one half of all hospital deaths in the United States. Sepsis has a high impact on health care in the US, with direct sepsis costs in 2009 exceeding $15.4 billion. A research study found that a 1-hour delay in appropriate antimicrobial care resulted in a 7% - 10% rise in mortality. Several professional societies seek to reduce sepsis mortality by targeting the timely use of diagnostic tests and antimicrobial therapy. The diagnostic instruments …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Fluid Dynamics Characterization Of Transcatheter Aortic Valves, Mohammed Barakat

Electronic Theses and Dissertations

Aortic stenosis due to degenerative calcific aortic valvular disease is the most reason for aortic valve replacement in developed countries. Aortic stenosis affects up to 7% of the world population, and current clinical data indicate that the number of the affected people could be triple by 2050, due to population ageing and health lifestyle. Transcatheter aortic valve replacement (TAVR) was introduced as a minimal invasive treatment of severe aortic stenosis. Even though surgical aortic valve replacement (SAVR) is considered the golden standard treatment for severe aortic stenosis patients, TAVR showed equivalent or even superior outcome compare to SAVR. Currently, transcatheter …

Tumor-Targeted Double Emulsions For Ultrasound-Triggered Delivery Of Molecular Therapeutics., Connor S Centner

Electronic Theses and Dissertations

Cancer is the second leading cause of death in the United States, with 1.74 million new cancer cases diagnosed and 610,000 cancer deaths expected in 2018 alone. Current treatments often result in negative systemic effects and ineffective treatment of the tumor. Drug delivery vehicles have been developed for more effective local delivery methods, but many drug delivery vehicles lack spatial and temporal control. Targeted double emulsions are a new class of drug delivery vehicles which present a promising option for a high payload and controlled delivery. The purpose of our project was to develop and characterize an aptamer-chelated double emulsion …

Probing The Effects Of Substrate Stiffness On Astrocytes Mechanics, Ariege Bizanti

Electronic Theses and Dissertations

Astrocytes are among the most functionally diverse population of cells in the central nervous system (CNS) as they are essential to many important neurological functions including maintaining brain homeostasis, regulating the blood brain barrier, and preventing build-up of toxic substances within the brain, for example. Astrocyte importance to brain physiology and pathology has inspired a host of studies focused on understanding astrocyte behavior primarily from a biological and chemical perspective. However, a clear understanding of astrocyte dysfunction and their link to disease has been hampered by a lack of knowledge of astrocyte behavior from a biomechanical perspective. Furthermore, astrocytes (and …

Mechanical Effects Of Surgical Adhesives On Ascending Thoracic Aortic Aneurysm Replacement, Dong Qiu

Electronic Theses and Dissertations

Ascending thoracic aortic aneurysm (aTAA) is a potentially lethal disease which grows gradually over time and may lead to aortic dissection and rupture. Currently, aTAA surgical repair using Dacron graft is a well-established treatment. In addition, surgical adhesives are frequently used in the surgeries to seal the anastomotic site. This study aims to investigate mechanical effects of four commonly used surgical adhesives, namely BioGlue, CoSeal, Crosseal, and Tisseel, on the suture site using in-vitro digital image correlation (DIC) method and finite element (FE) simulations in an ovine model. In this study, first, mechanical properties of ovine ascending aorta were obtained …

Development Of A Computational Approach To Assess Hip Fracture And Repair: Considerations Of Intersubject And Surgical Alignment Variability, Azhar Ali

Electronic Theses and Dissertations

Hip fracture remains a major public health concern due to the significant number of occurrences and mortality rates. Intertrochanteric fractures are the most common type of fracture and are typically caused by a fall. Intramedullary osteosynthesis is a common surgical practice to repair intertrochanteric fractures, but revisions are often required. The work presented in this thesis aims to improve the realism and fidelity of computational models of hip fracture, which can be an effective alternative to costly and labor-intensive clinical in-vivo and experimental in-vitro testing. Intersubject variability is inherently present in anatomy and material relations. Statistical shape and intensity models …