Engineering Commons^™

Combining Adhesive And Nonadhesive Injectable Hydrogels For Intervertebral Disc Repair In An Ovine Discectomy Model., Christopher J Panebianco, Caroline Constant, Andrea J. Vernengo, Dirk Nehrbass, Dominic Gehweiler, Tyler J Distefano, Jesse Martin, David J Alpert, Saad B Chaudhary, Andrew C Hecht, Alan C Seifert, Steven B Nicoll, Sibylle Grad, Stephan Zeiter, James C Iatridis

Henry M. Rowan College of Engineering Faculty Scholarship

BACKGROUND: Intervertebral disc (IVD) disorders (e.g., herniation) directly contribute to back pain, which is a leading cause of global disability. Next-generation treatments for IVD herniation need advanced preclinical testing to evaluate their ability to repair large defects, prevent reherniation, and limit progressive degeneration. This study tested whether experimental, injectable, and nonbioactive biomaterials could slow IVD degeneration in an ovine discectomy model.

METHODS: Ten skeletally mature sheep (4-5.5 years) experienced partial discectomy injury with cruciate-style annulus fibrosus (AF) defects and 0.1 g nucleus pulposus (NP) removal in the L1-L2, L2-L3, and L3-L4 lumbar IVDs. L4-L5 IVDs were Intact controls. IVD injury …

Ti-6al-4v Β Phase Selective Dissolution: In Vitro Mechanism And Prediction, Michael A Kurtz

All Dissertations

Retrieval studies document Ti-6Al-4V β phase dissolution within total hip replacement systems. A gap persists in our mechanistic understanding and existing standards fail to reproduce this damage. This thesis aims to (1) elucidate the Ti-6Al-4V selective dissolution mechanism as functions of solution chemistry, electrode potential and temperature; (2) investigate the effects of adverse electrochemical conditions on additively manufactured (AM) titanium alloys and (3) apply machine learning to predict the Ti-6Al-4V dissolution state. We hypothesized that (1) cathodic activation and inflammatory species (H₂O₂) would degrade the Ti-6Al-4V oxide, promoting dissolution; (2) AM Ti-6Al-4V selective dissolution would occur …

Controlled Manipulation And Transport By Microswimmers In Stokes Flows, Jake Buzhardt

All Dissertations

Remotely actuated microscale swimming robots have the potential to revolutionize many aspects of biomedicine. However, for the longterm goals of this field of research to be achievable, it is necessary to develop modelling, simulation, and control strategies which effectively and efficiently account for not only the motion of individual swimmers, but also the complex interactions of such swimmers with their environment including other nearby swimmers, boundaries, other cargo and passive particles, and the fluid medium itself. The aim of this thesis is to study these problems in simulation from the perspective of controls and dynamical systems, with a particular focus …

Determining The Effects Of Glycocalyx Modifications On The Electrophysical Properties Of Human Mesenchymal Stem Cells, Rominna E. Valentine Ico

Electronic Theses, Projects, and Dissertations

Human mesenchymal stem cells (hMSCs) have gained popularity in clinical trials due to their multipotent differentiation characteristics, ability to secrete bioactive molecules, migrate into diseased or damaged tissues, and their immunosuppressive properties. HMSC cultures are heterogeneous, containing stem cells, partially differentiated progenitor cells, and fully differentiated cells. One of the major challenges with hMSCs therapeutic potential is the inability to select specific cell subpopulations due to an insufficient number of biomarkers. Often the biomarkers used, like those for fluorescence-activated cell sorting, are not sufficient to define hMSCs because they overlap with other cell types. Consequently, there is a need to …

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

McKelvey School of Engineering 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 …

Improving And Integrating Quantitative Single Cell Spatial Biology For Theranostic Medicine, Peng Lu

McKelvey School of Engineering Theses & Dissertations

Disease states are the result of a complex interplay of many different cell types interacting in close proximity in the context of often heterogeneous tissues. Alpha particles are drawing intense research and clinical interest because of their potent cytotoxic effects and their short path lengths. Analyzing the dose distribution and tissue micro-environment for alpha therapy plays a key role in predicting the efficacy of this targeted radiotherapy. However, to date there have been no direct on-tissue analytical methods for alpha dose distributions and the corresponding tissue microenvironments.

Therefore, we have developed a pipeline to overcome this limitation by utilizing quantitative …

Deep Learning And Generative Ai Approaches For Automated Diagnosis And Personalized Treatment: Bridging Machine Learning, Medicine, And Biomechanics In Predicting Tissue Mechanics And Biomaterial Properties., Yasin Shokrollahi

Theses and Dissertations

Machine learning, particularly deep neural networks, has demonstrated significant potential in predicting high-dimensional tasks across various domains. This work encompasses a detailed review of Generative AI in healthcare and three studies integrating machine learning with finite element analysis for predicting biomechanical behaviors and properties. Initially, we provide a comprehensive overview of Generative AI applications in healthcare, focusing on Transformers and Denoising Diffusion models and suggesting potential research avenues to address existing challenges.

Subsequently, we addressed soccer-related ocular injuries by combining finite element analysis and machine learning to predict retinal mechanics following a soccer ball hit rapidly. The prediction errors are …

Effects Of Indole Derivative Idc16 On Cell Proliferation, Transfection, And Alternative Splicing In Production Of Lentiviral Vectors By Transient Co-Transfection, Nataly Mier

All Graduate Theses and Dissertations, Fall 2023 to Present

Viruses can efficiently introduce genetic material into a variety of cells through cell infection. Therefore, viral vectors, defined as virus-based gene delivery systems, effectively transfer functional gene constructs to target cells. Among different viral vectors, lentiviral vectors are of interest due to the advantages offered to research and therapeutic applications. Low productivity of lentiviral vectors in mammalian producer cells and high production cost, however, remain barriers to the vectors’ routinary use, particularly in clinical settings.

Since most lentiviral vectors are derived from human immunodeficiency virus type I, their genome has been engineered to increase safety. Nevertheless, modifications of the lentiviral …

Process-Structure-Property Relationships Of Nanofibers For Biomedical Applications, Dipasree Bhowmick

Theses and Dissertations

This thesis explores the fabrication, characterization, and applications of nanofiber membranes utilizing Forcespinning® technology. Two distinct nanofiber systems were developed and evaluated, one focusing on pH-responsive Eudragit-baicalin loaded nanofibrous membranes for wound healing and the second one on thermo-responsive nanofiber-hydrogel (PNIPAAm) systems for biosensing applications, specifically dopamine detection. In the first project, nanofiber membranes loaded with Eudragit and baicalin demonstrated superior antibacterial properties against both gram-negative (E. coli) and gram-positive (B. meg) bacteria. Additionally, these membranes exhibited antioxidant properties and enhanced cell proliferation of 3TT cells, making them promising candidates for wound healing dressings. In the second project, a …

Characterizing Intervertebral Disc Strain Under Dynamic Loading Conditions Using Ultrasound Texture Analysis, Radhika Kulkarni

Discovery Undergraduate Interdisciplinary Research Internship

Herniated discs in the spine are a significant patient burden, with potential links to lower back and leg discomfort and a considerable impact on daily life. These discs, located between spinal vertebrae, are comprised of the annulus fibrosus (AF) and the nucleus pulposus (NP). Herniations happen when the NP protrudes through a full-thickness annular tear, possibly compressing spinal nerves. The mechanical factors underlying herniated discs are poorly understood, necessitating research into these mechanisms and accessible diagnostic techniques. Our study employs high-resolution ultrasound and texture correlation to quantify strain patterns in intervertebral discs during dynamic loading.

A motion segment from the …

Controlled Radiation Capsule For Precision And Rapid Cancer Treatment, Hoseon Lee, Zsolt Kollar, Bailey R. White, Junia Nguyen, David Roque, Sowjanya Palagani

Symposium of Student Scholars

This research aims to transform cancer treatment through the optimization of brachytherapy, with a focus on reducing treatment duration, setup complexities, and financial burdens, all while emphasizing patient safety. Patients living at a distance from radiation clinics, particularly those undergoing extended Low Dose Radiation brachytherapy, often struggle with the formidable financial challenges associated with securing nearby accommodations. In response to these issues, the research introduces a radiation capsule designed to condense the conventional six-month treatment period to approximately just one week, thereby significantly reducing the duration of required accommodations. This capsule is especially relevant considering the construction cost of $40 …

Deep Multi-Stage System For Liver And Lesions Segmentation Using Ct Images, Nermeen Elmenabawy, Mervat El-Seddek, Hossam El-Din Moustafa, Ahmed Elnakib

Mansoura Engineering Journal

Accurate tumor segmentation plays a pivotal role in cancer diagnosis and treatment planning. This study introduces an automated system for segmenting liver and tumors in CT images through a multi-stage process. Initial preprocessing improves image quality, followed by feature extraction using pretrained VGG16-Segnet and FCNAlexnet models. Outputs from both models are combined using a parallel fusion operation. Finally, pixel-wise classification designates pixels as liver, tumor, or background. Evaluation on the MICCAI'2017 LiTS database yielded a Dice coefficient of 95.3% for liver and 78.1% for tumors using 5-fold cross-validation. Comparative studies highlight the superior accuracy of our approach in liver and …

Occlusive Membranes For Guided Regeneration Of Inflamed Tissue Defects., Woojin Choi, Utkarsh Mangal, Jin-Young Park, Ji-Yeong Kim, Taesuk Jun, Ju Won Jung, Moonhyun Choi, Sungwon Jung, Milae Lee, Ji-Yeong Na, Du Yeol Ryu, Jin Man Kim, Jae-Sung Kwon, Won-Gun Koh, Sangmin Lee, Patrick T J Hwang, Kee-Joon Lee, Ui-Won Jung, Jae-Kook Cha, Sung-Hwan Choi, Jinkee Hong

Henry M. Rowan College of Engineering Faculty Scholarship

Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration …

The Effects Of Engineering Summer Camps On Middle And High School Students’ Engineering Interest And Identity Formation: A Multi-Methods Study, Timothy Robinson, Adam Kirn, Jenny Amos, Indira Chatterjee

Journal of Pre-College Engineering Education Research (J-PEER)

This multi-methods study explores changes in engineering interest and identity of middle and high school students (n = 79) attending introductory-level engineering summer camps at a large western land grant university. Middle school is a critical time when student interest, identity, and subsequently career choice begin to emerge and hence it is important that at this age students are given accurate information about engineering majors in college and future career opportunities in engineering. Data were collected over a period of two years in six summer camps. Three separate populations of middle and high school students participated in the summer …

Real-Time Arrhythmia Detection Using Convolutional Neural Networks, Thong Vu, Tyler Petty, Kemal Yakut, Muhammad Usman, Wei Xue, Francis M. Haas, Robert A. Hirsh, Xinghui Zhao

Henry M. Rowan College of Engineering Faculty Scholarship

Cardiovascular diseases, such as heart attack and congestive heart failure, are the leading cause of death both in the United States and worldwide. The current medical practice for diagnosing cardiovascular diseases is not suitable for long-term, out-of-hospital use. A key to long-term monitoring is the ability to detect abnormal cardiac rhythms, i.e., arrhythmia, in real-time. Most existing studies only focus on the accuracy of arrhythmia classification, instead of runtime performance of the workflow. In this paper, we present our work on supporting real-time arrhythmic detection using convolutional neural networks, which take images of electrocardiogram (ECG) segments as input, and classify …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Optimizing Channel Formation In Peg Maleimide Hydrogels, Bakthavachalam Kannadasan

Masters Theses

Blood vessels including the arteries, veins, and capillaries are a critical and indispensable component of various organisms. Some studies estimate that if all the blood vessels present in our body are arranged in line, they would amount to a total length of approximately 60,000 miles. This distance is enough to circle the world two and a half times! In addition to being all pervasive, blood vessels perform certain key functions such as delivery of oxygen and nutrients to various tissues in the body. They also assist in the spread of diseases such as cancer. Therefore, it is important to study …

Electrostatic Effects On Lipid Bilayer Physicochemal Properties And Vesicle Adhesion, Oscar Zabala-Ferrera

Doctoral Dissertations

Lipids are an integral part of cells, being the principal component of the cell membrane, and contributing to the function and regulation of biological processes. Lipid nanoparticles mimicking a cell’s endosomes or exosomes are of particular interest within the pharmaceutical industry for their ability to deliver cargo such as RNA into target cells. The delivery process faces a multitude of challenges, so a rational design approach for vesicles that considers a lipid’s physicochemical contribution to the membrane is desired. To that end, this thesis explores the creation of large area biomembranes along with the development of electromechanical and optical characterization …

Differential Impact Of Blood Pressure Control Targets On Epicardial Coronary Flow After Transcatheter Aortic Valve Replacement, Brennan Vogl, Alejandra Chavez-Ponce, Adam Wentworth, Eric Erie, Pradeep Yadav, Vinod H. Thourani, Lakshmi Prasad Dasi, Brian Lindman, Mohamad Alkhouli, Hoda Hatoum

Michigan Tech Publications, Part 2

Background: The cause for the association between increased cardiovascular mortality rates and lower blood pressure (BP) after aortic valve replacement (AVR) is unclear. This study aims to assess how the epicardial coronary flow (ECF) after AVR varies as BP levels are changed in the presence of a right coronary lesion. Methods: The hemodynamics of a 3D printed aortic root model with a SAPIEN 3 26 deployed were evaluated in an in vitro left heart simulator under a range of varying systolic blood pressure (SBP) and diastolic blood pressure (DBP). ECF and the flow ratio index were calculated. Flow index value …

Head Impact Effects In Small Remotely Piloted Aircraft System (Srpas) Collisions: Gender Specific Risks And Vulnerable Population Protection, Md Farhan Hoque Sagar

Electronic Thesis and Dissertation Repository

This study focuses on supporting the development of safety regulations for vulnerable populations during drone to head impacts. First, the small female head and neck model was compared to cadaveric data. Then, combined with lab’s previous work, gender-based disparities in head impact responses were highlighted, with small females experiencing higher injury risk metrics, despite lower skull von Mises stress. Beyond small females, children of various ages and their head responses during impacts were also analyzed. In addition to the previously developed quadcopter drone model, a new Mavic Pro drone model was developed, and this model was integrated with human head …

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …

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.

Multicellular And Multiscale Models Of Microbes And Host Systems, Elebeoba May

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

S-Net: A Multiple Cross Aggregation Convolutional Architecture For Automatic Segmentation Of Small/Thin Structures For Cardiovascular Applications, Nan Mu, Zonghan Lyu, Mostafa Rezaeitaleshmahalleh, Cassie Bonifas, Jordan Gosnell, Marcus Haw, Joseph Vettukattil, Jingfeng Jiang

Michigan Tech Publications, Part 2

With the success of U-Net or its variants in automatic medical image segmentation, building a fully convolutional network (FCN) based on an encoder-decoder structure has become an effective end-to-end learning approach. However, the intrinsic property of FCNs is that as the encoder deepens, higher-level features are learned, and the receptive field size of the network increases, which results in unsatisfactory performance for detecting low-level small/thin structures such as atrial walls and small arteries. To address this issue, we propose to keep the different encoding layer features at their original sizes to constrain the receptive field from increasing as the network …

Novel Method Of The Quantification Of Turbulent Fluid Flow In Silicone Artery Phantoms Using Acoustic Analysis, Julia Wong

Master's Theses

Cardiovascular disease is the leading cause of death globally and is responsible for taking 17.9 million lives per year. Despite the use of clinical treatments and detection methods, there remains a large population of individuals that suffer from CVD whose symptoms are left undetected and untreated prior to a life-threatening cardiac event. This highlights a need for an early detection method that can prevent the manifestation and worsening of the disease as well as address limitations of current early detection methods. An area of interest for early detection of CVD is subclinical atherosclerosis, which is the long, early, asymptomatic stage …

Microbial Glycosylation Of Antitubercular Agent Chlorflavonin, Jie Ren, Jixun Zhan

Biological Engineering Faculty Publications

Flavonoids have shown health-benefiting properties, such as antioxidative and anti-inflammatory activities, and are commonly used as nutraceuticals and pharmaceuticals. Although flavonoids are predominantly identified from plants, several filamentous fungal species have also been reported to produce bioactive flavonoids, including chlorflavonin from Aspergillus candidus, a novel halogenated flavonoid with potent antifungal and antitubercular (anti-TB) activities. Unfortunately, the low water-solubility of this molecule may hinder its bioavailability. Glycosylation is an effective method to enhance the polarity of natural products and alter their physicochemical properties. This work focuses on the development of novel water-soluble chlorflavonin derivatives to combat the threat of drug-resistant …

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 …

Exploration Of Motion Capture System To Investigate Human Shoulder Kinematics, Ola Alsaadi

Electronic Theses and Dissertations

The glenohumeral joint (GH) is commonly conceptualized as a ball-and-socket joint [1], and its center of rotation (COR) is presumed to coincide with the geometric center of the medial-superior region of the humeral head [2]. Recent research has endorsed improvements in COR estimation through invasive and noninvasive techniques, including cadaver studies, stereophotogrammetry, and motion capture (MOCAP) systems. Despite increased interest in wearable technology within human movement analysis, the problem of COR estimation employing MOCAP systems and its validation against bi-planar fluoroscopy remains relatively unexplored.

This study employed a marker-based MOCAP system to compare the accuracy, error, and precision of three …

Digital Twins Of The Living Knee: From Measurements To Model, Thor Erik Andreassen

Electronic Theses and Dissertations

Modern medicine has dramatically improved the lives of many. In orthopaedics, robotic surgery has given clinicians superior accuracy when performing interventions over conventional methods. Nevertheless, while these and many other methods are available to ensure treatments are performed successfully, far fewer methods exist to predict the proper treatment option for a given person. Clinicians are forced to categorize individuals, choosing the best treatment on “average.” However, many individuals differ significantly from the “average” person, for which many of these treatments are designed. Going forward, a method of testing, evaluating, and predicting different treatment options' short- and long-term effects on an …