Biomedical Engineering and Bioengineering Commons^™

Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression And Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury In K18-Hace2 Transgenic Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, John D. Catravas

Bioelectrics Publications

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome. and increasing mortality. To investigate the mechanisms behind this interaction, we developed a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and are kept on an …

The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas

Bioelectrics Publications

Hydrochloric acid (HCl) exposure causes asthma-like conditions, reactive airways dysfunction syndrome, and pulmonary fibrosis. Heat Shock Protein 90 (HSP90) is a molecular chaperone that regulates multiple cellular processes. HSP90 inhibitors are undergoing clinical trials for cancer and are also being studied in various pre-clinical settings for their anti-inflammatory and anti-fibrotic effects. Here we investigated the ability of the heat shock protein 90 (HSP90) inhibitor AT13387 to prevent chronic lung injury induced by exposure to HCl in vivo and its protective role in the endothelial barrier in vitro. We instilled C57Bl/6J mice with 0.1N HCl (2 µL/g body weight, intratracheally) and …

The Paradox Of Pulmonary Vascular Resistance: Restoration Of Pulmonary Capillary Recruitment As A Sine Qua Non For True Therapeutic Success In Pulmonary Arterial Hypertension, David Langleben, Stylianos E. Orfanos, Benjamin D. Fox, Nathan Messas, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension …

In Vitro And In Vivo Correlation Of Skin And Cellular Responses To Nucleic Acid Delivery, M. Bosnjak, K. Znidar, A. Sales Conniff, T. Jesenko, B. Markelc, Nina Semenova, J. Tur, K. Kohena, S. Kranjc Brezar, L. Heller, M. Cemazar

Bioelectrics Publications

Skin, the largest organ in the body, provides a passive physical barrier against infection and contains elements of the innate and adaptive immune systems. Skin consists of various cells, including keratinocytes, fibroblasts, endothelial cells and immune cells. This diversity of cell types could be important to gene therapies because DNA transfection could elicit different responses in different cell types. Previously, we observed the upregulation and activation of cytosolic DNA sensing pathways in several non-tumor and tumor cell types as well in tumors after the electroporation (electrotransfer) of plasmid DNA (pDNA). Based on this research and the innate immunogenicity of …

Biomarkers Of Inflammation And Oxidative Stress In The Prediction And Management Of Acute Coronary Syndrome, Udaya Ralapanawa, Sivakanesan R

Health Sciences

The assessment of patients presenting with chest pain or symptoms indicative of cardiac ischemia remains a diagnostic challenge. Many types of research have focused on the search for ideal biological markers for the rapid detection of cardiac cell injuries. Markers of inflammation and oxidative stress are the way forward. At present, the biomarker most widely used for diagnosing acute coronary syndrome is cardiac troponin though it has some limitations. Apart from cardiac troponin, several other biomarkers, especially inflammation and oxidative stress markers in acute coronary syndrome, have been investigated. However, most of them still require validation in further studies. As …

Eye Movement And Pupil Measures: A Review, Bhanuka Mahanama, Yasith Jayawardana, Sundararaman Rengarajan, Gavindya Jayawardena, Leanne Chukoskie, Joseph Snider, Sampath Jayarathna

Computer Science Faculty Publications

Our subjective visual experiences involve complex interaction between our eyes, our brain, and the surrounding world. It gives us the sense of sight, color, stereopsis, distance, pattern recognition, motor coordination, and more. The increasing ubiquity of gaze-aware technology brings with it the ability to track gaze and pupil measures with varying degrees of fidelity. With this in mind, a review that considers the various gaze measures becomes increasingly relevant, especially considering our ability to make sense of these signals given different spatio-temporal sampling capacities. In this paper, we selectively review prior work on eye movements and pupil measures. We first …

Electroporation And Cell Killing By Milli- To Nanosecond Pulses And Avoiding Neuromuscular Stimulation In Cancer Ablation, Emily Gudvangen, Vitalii Kim, Vitalij Novickij, Federico Battista, Andrei G. Pakhomov

Bioelectrics Publications

Ablation therapies aim at eradication of tumors with minimal impact on surrounding healthy tissues. Conventional pulsed electric field (PEF) treatments cause pain and muscle contractions far beyond the ablation area. The ongoing quest is to identify PEF parameters efficient at ablation but not at stimulation. We measured electroporation and cell killing thresholds for 150 ns–1 ms PEF, uni- and bipolar, delivered in 10- to 300-pulse trains at up to 1 MHz rates. Monolayers of murine colon carcinoma cells exposed to PEF were stained with YO-PRO-1 dye to detect electroporation. In 2–4 h, dead cells were labeled with propidium. Electroporation and …

Reporter Chondrocyte Optimization Of Bioinks For Zonal 3d Bioprinting Of Cartilage, Kari Martyniak

Electronic Theses and Dissertations, 2020-2023

Osteoarthritis (OA) is the most common form of arthritis, often thought of as a disease of the elderly, but post traumatic OA predominantly impacts younger individuals. Articular cartilage is the tissue that coats the end of your bones in synovial joints. Since cartilage has limited healing capacity, defects, or injuries to it progressively erodes down to the subchondral bone. Unfortunately, current treatment options all have limitations, particularly for younger patients. Cartilage has a specific zonal architecture that is distinguished by the different cell morphologies and arrangements, biochemical composition, and mechanical properties. 3D bioprinting is a tissue engineering technique that involves …

Atmospheric Air Plasma Streamers Deliver Nanosecond Pulses For Focused Electroporation, Shu Xiao, Carol Zhou, Eric Appia, Shirshak Dhali

Bioelectrics Publications

Background: For electrotherapies that involve electrodes and high-intensity electric fields, such as in tissue ablation, we report a method of pulse delivery that can focus the electric field away from the electrodes, as demonstrated in vitro.

Materials and Methods: To electroporate cells in a monolayer seeded in a 35 mm culture dish, two atmospheric-pressure plasma channels generated by two thin, copper foil electrodes above the surface of the solution provided the current and established the electric field.

Results: Depending on the pulse duration, the plasma channels were observed as corona (100 ns), streamer (300 ns), and mixture of streamer …

Alkaline Plasma-Activated Water (Paw) As An Innovative Therapeutic Avenue For Cancer Treatment, Bolun Pang, Zhijie Liu, Sitao Wang, Yuting Gao, Miao Qi, Dehui Xu, Renwu Zhou, Dingxin Liu, Michael G. Kong

Bioelectrics Publications

Plasma-activated water (PAW) is considered to be an effective anticancer agent due to the diverse aqueous reactive oxygen and nitrogen species (RONS: ROS and RNS), but the drawback of low dose and short duration of RONS in acidified PAW limits their clinical application. Herein, this Letter presents an innovative therapeutic avenue for cancer treatment with highly-effective alkaline PAW prepared by air surface plasma. This anticancer alkaline formulation is comprised of a rich mixture of highly chemical RONS and exhibited a prolonged half-life compared to acidified PAW. The H₂O₂, NO₂-, and ONOO^-/O_{2 …}

Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide …

Design And Synthesis Of Α-Anomeric Diacetylene-Containing Glycosides As Photopolymerizable Molecular Gelators, Guijun Wang, Dan Wang, Anji Chen, Ifeanyi S. Okafor, Lalith Palitha Samankumara

Chemistry & Biochemistry Faculty Publications

Glycolipids with diacetylene functional groups are fascinating compounds with many practical uses. Among these, diacetylene-containing gelators are especially important because they can form photopolymerizable gels, which are useful stimuli-responsive materials. Inspired by the unique properties of diacetylene-containing gelators and to understand the structural influences especially the location of the diacetylene functional groups on the self-assembling properties, a series of 15 novel N-acetyl-d-glucosamine derivatives with the diacetylene functional group introduced at the anomeric position were designed and synthesized. The diacetylene function is attached to the sugar through α-glycosylation with the distance from the anomeric oxygen being varied from one, two, …

Theta Burst Brain Stimulation In Painful Diabetic Neuropathy Patients: Investigating Neural Mechanisms, Bhushan Thakkar

Theses and Dissertations

Chronic pain (CP) is a significant contributor to disability and disease burden globally. In 2019, approximately 50.2 million adults (20.4% of the US population) experienced chronic pain, contributing to $560-635 billion in direct medical costs. In addition, the worldwide prevalence of diabetes mellitus has reached epidemic proportions and is set to increase to 629 million by 2045. Almost 50% of patients with diabetes present with diabetic neuropathy (DN), and one in five patients with diabetes presents with painful DN (pDN) which is the most common cause of neuropathic pain (NP) in the US. Symptomatic treatment is the mainstay of management …

Exosome- And Microrna-Based Therapeutic Approach For Tendinopathy, Angela Wang Ilaltdinov

Dissertations and Theses

Tendinopathy, characterized by degeneration and chronic inflammation, is a significant clinical burden. Current treatments focus on symptom management but do not sufficiently address its underlying pathology; however, stem cell-based approaches aimed at repairing diseased tissues may overcome this limitation. Therapeutic effects of stem cells may be due in part to paracrine actions, including some mediated by exosomes – extracellular vesicles secreted by cells that play a role in cell communication. MicroRNA (miRNA), small non-coding RNA carried by exosomes, are likely responsible for many exosome effects. Exosomes and miRNA therapies show promise in treating diseases such as cancer and arthritis, but …

Modeling Of Patient-Specific Periaortic Mechanics And Pulmonary Artery Hemodynamics Based On Phase-Contrast Magnetic Resonance Imaging Sequences., Johane H. Bracamonte

Theses and Dissertations

Inverse modeling in cardiovascular medicine is a collection of methodologies that can provide non-invasive patient-specific estimations of clinical risk factors using medical imaging as inputs. Its incorporation into clinical practice has the potential to improve diagnosis and treatment planning with low associated risks and costs.

Herein, three different phase contrast magnetic resonance imaging (MRI) modalities were implemented as input data, displacement encoding with stimulated echoes (DENSE MRI) applied, and time-resolved velocity encoding phase-contrast MRI, in 1D and 3D, applied to pulmonary artery (PA) hemodynamics.

A model to account for the effect of periaortic interactions due to static and dynamic structures …

Therapeutic Approaches For Respiratory Distress Syndrome, Franck J. Kamga Gninzeko

Theses and Dissertations

Respiratory distress syndrome (RDS) is characterized by shortness of breath and low oxygen levels. RDS affects the neonatal and adult populations. In the neonatal population, RDS can be classified as NRDS (Neonatal respiratory distress syndrome), while in adults, it is known as ARDS (acute respiratory distress syndrome). This dissertation examines a therapeutic approach to NRDS and a mechanistic approach to ARDS with in vivo and in vitro models of lung injury. NRDS is characterized by a deficiency or lack of surfactant. Surfactant is an essential compound composed of phospholipids and proteins to prevent the lungs from collapsing. There are several …

Exploring Cell Differentiation Vs. Localization In Engineered Ligament-To-Bone Entheses, Saagar N. Sheth, Michael E. Brown, Jennifer L. Puetzer

UROP Posters

The anterior cruciate ligament (ACL) connects to bone via structurally complex insertions known as entheses that translate load from elastic ligament and stiff bone via gradients in organization, composition, and cell phenotype [1]. These gradients are not recreated in graft repair or engineered replacements, yielding limited repair options and high failure rates [2]. Previously, we developed a culture system that uses a tensile-compressive interface to guide ligament fibroblasts to develop early postnatal-like entheses by 6 weeks [3]; however, cells used were isolated from the entirety of the neonatal bovine ACL from bone to bone and likely contained multiple cell phenotypes …

Neuromotor Changes In Participants With A Concussion History Can Be Detected With A Custom Smartphone App, Christopher K. Rhea, Masahiro Yamada, Nikita A. Kuznetsov, Jason T. Jakiela, Chanel T. Lojacono, Scott E. Ross, F. J. Haran, Jason M. Bailie, W. Geoffrey Wright

Rehabilitation Sciences Faculty Publications

Neuromotor dysfunction after a concussion is common, but balance tests used to assess neuromotor dysfunction are typically subjective. Current objective balance tests are either cost- or space-prohibitive, or utilize a static balance protocol, which may mask neuromotor dysfunction due to the simplicity of the task. To address this gap, our team developed an Android-based smartphone app (portable and cost-effective) that uses the sensors in the device (objective) to record movement profiles during a stepping-in-place task (dynamic movement). The purpose of this study was to examine the extent to which our custom smartphone app and protocol could discriminate neuromotor behavior between …

Load Sharing Assessment Of Osseoligamentous Structures Within A Thoracic Spine Segment During Surgical Release, Michael Polanco, James Bennett, Austin Tapp, Michel Audette, Stacie Ringleb, Sebastian Bawab

Electrical & Computer Engineering Faculty Publications

Spinal surgical procedures often require release of intervertebral discs and ligaments to optimally achieve postural correction on a patient-specific basis. In this paper, a T7-T8 Finite Element (FE) model is utilized to examine internal load sharing during resection steps performed in a Ponte osteotomy. The FE model was rotated bidirectionally along three anatomical planes using an externally applied moment. In each step, the Ranges of Motion (RoM), Instantaneous Centers of Rotation (ICR), and forces from ligaments, discs, facet, and costovertebral joints were calculated. The product of each component’s force and the distance between the ICR and their position were used …

An Antimicrobial Polydopamine Surface Coating To Reduce Biofouling On Telemetry Tags Used In Marine Conservation Practices, Ariana Smies

Dissertations, Master's Theses and Master's Reports

Satellite telemetry tags are used to track the migration patterns of large cetaceans. These tags penetrate the dermis and remain embedded in the underlying blubber tissue. As the dermis of cetaceans is host to a diverse microbiome, and it is impossible to clean the skin before implanting the devices, the potential for infection is increased when the tags penetrate through the skin. H₂O₂ is a potential antimicrobial agent that, in addition to showing broad-spectrum efficacy against gram-negative and gram-positive bacteria, can promote wound healing outcomes by promoting proliferative factors and peptides that protect against oxidative stress. However, …

The Rotator Cuff Tendon-To-Bone Interface: Maturation, Aging, And 3d Bioprinting For Regeneration, Xiping Jiang

Theses & Dissertations

Rotator cuff tendon injuries often occur at the tendon-to-bone interface (i.e., enthesis) area with a high prevalence for the elderly population. In addition, regeneration of the gradient structure of the enthesis is still a significant clinical challenge. Our studies aim to identify the histological, molecular, and biomechanical alterations of the rotator cuff enthesis with maturation and aging, and develop a novel therapeutic method using three-dimensional (3D) bioprinting technique to regenerate a functional enthesis. Striking variations of the entheses were observed both histologically and biomechanically during the maturation process. The histological features did not show many differences at the insertion site …

Deep Learning Approach To Improved Image Quality For Medical Diagnostics, Olivia Loesch, Katie Leyba, Halyley Chan, Craig Goergen

Discovery Undergraduate Interdisciplinary Research Internship

The United Nation’s health-related Sustainable Development Goals are difficult to achieve in low- and middle-income countries due to workforce shortages and inadequate health surveillance systems. However, with the growth of artificial intelligence (AI) and computer algorithms, it is possible to apply AI to healthcare technologies to improve progress towards these UN standards. This project aims at using and improving computer algorithms and deep learning to aid in the extraction of important structural and functional information from murine carotid artery ultrasound and photoacoustic images. First, we created a large database of simulated photoacoustic images to optimize the algorithms. These images were …

Novel Approaches For Enhancing Cell Survival And Function In Vivo, Ou Wang

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

FDA has approved several cell-based therapeutics and hundreds of cell therapy clinical trials are ongoing. Cells will be a significant type of medicine after small molecule and protein drugs. However, several obstacles need to be addressed to achieve the widespread use of cellular therapeutics. The first challenge is the low efficacy of cell transplantation due to low retention, survival, integration, and function of cells in vivo. The second challenge is producing a massive number of cells for clinical treatment with cost-effectively and reproducibly technologies.

In this thesis, we proposed and investigated two approaches to address these challenges. To begin …

Advanced Risk Models To Predict Surgical Site Infections Using Machine Learning Approaches And Risk-Adjusted Control Charts, Rabia Emhamed Al Mamlook

Dissertations

Even though most infections are treatable with antibiotics, Surgical Site Infections (SSIs) remain a significant healthcare problem as they increase hospital stays, require additional treatments, reduce a patient’s quality of life, and increase morbidity and mortality. To reduce the risks and to encourage the highest quality healthcare, it is important to measure, predict, and monitor the risk of SSIs. Preoperative prediction of SSIs is essential to facilitate the implementation of preventative strategies for high-risk patients. The overarching goal of this dissertation is to investigate new opportunities of using machine-learning (ML) to improve the accuracy and use of pre-operative prediction models …

3-In-1 Medical Lancet, Jonathan J. Panella, Gage Vogtlin, Marissa Koski, Benjamin Neyland

Mechanical Engineering

First responders need a quick, sterile, and convenient way to sample blood for glucose testing because glucose levels are a vital metric in assessing time-critical emergency situations. The blood sampling process consists of pre-sterilizing the sample site on the skin with an alcohol pad, pricking the skin with a lancet, and lastly, after sampling, putting a bandage over the prick site. The scope of this project is to design a device which integrates and streamlines the use of the three sub-processes (sterilization, lancing, and bandaging) while upholding the necessary requirements of a single-use medical device and considering other factors which …

Siderophore-Mediated Zinc Acquisition Enhances Enterobacterial Colonization Of The Inflamed Gut, Judith Behnsen, Hui Zhi, Allegra T. Aron, Venkateswaran Subramanian, William Santus, Michael H. Lee, Romana R. Gerner, Daniel Petras, Janet Z. Liu, Keith D. Green, Sarah L. Price, Jose Camacho, Hannah Hillman, Joshua Tjokrosurjo, Nicola P. Montaldo, Evelyn M. Hoover, Sean Treacy-Abarca, Benjamin A. Gilston, Eric P. Skaar, Walter J. Chazin, Sylvie Garneau-Tsodikova, Matthew B Lawrenz, Robert D Perry, Sean-Paul Nuccio, Pieter C. Dorrestein, Manuela Raffatellu

Pharmacy Nuclear Magnetic Resonance Center Faculty Publications

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the …

Effects Of Il-10 On Local Cell Populations And Functional Recovery Following Vml Injury, Zain Blackwell

Biomedical Engineering Undergraduate Honors Theses

Volumetric muscle loss (VML) injuries are prevalent in both military personnel suffering from battlefield related incidents, and civilians following severe motor accidents. Despite its prevalence, VML has no pro-regenerative clinical treatments in place to recover some of the functional capabilities of the damaged muscle. Free flap grafting, debridement of damaged tissue, and physical therapy are the only clinical standards available that offer little functional recovery benefits, even after years of consistent treatment. In this study, anti-inflammatory cytokine interleukin-10 in conjunction with autologous minced muscle was assessed as a possible treatment for VML injuries and its influences on cellular behavior within …

Generation, Analysis, And Evaluation Of Patient-Specific, Osteoligamentous, Spine Meshes, Austin R. Tapp

Biomedical Engineering Theses & Dissertations

Scoliosis, an abnormal curvature of the spine, is traditionally corrected with bracing treatments or by a highly invasive posterior spinal fusion (PSF) operation. These correction strategies are constrained by current imaging modalities, which fail to elucidate the soft tissue anatomy that is known to play a critical role in spinal stiffness and overall structure. Osteoligamentous segmentations of the spinal column offer a foundation for downstream finite element (FE) studies seeking to optimize bracing treatments or determine ideal surgical approaches.

This thesis presents methods for automatically and semi-automatically segmenting vertebrae and surrounding soft tissues of the spinal column using X-ray computed …

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

Deep Learning Predicts Ebv Status In Gastric Cancer Based On Spatial Patterns Of Lymphocyte Infiltration, Baoyi Zhang, Kevin Yao, Min Xu, Jia Wu, Chao Cheng

Computer Vision Faculty Publications

EBV infection occurs in around 10% of gastric cancer cases and represents a distinct subtype, characterized by a unique mutation profile, hypermethylation, and overexpression of PD-L1. Moreover, EBV positive gastric cancer tends to have higher immune infiltration and a better prognosis. EBV infection status in gastric cancer is most commonly determined using PCR and in situ hybridization, but such a method requires good nucleic acid preservation. Detection of EBV status with histopathology images may complement PCR and in situ hybridization as a first step of EBV infection assessment. Here, we developed a deep learning-based algorithm to directly predict EBV infection …