Biomedical Engineering and Bioengineering Commons^™

Development Of A Crosslinked Osteochondral Xenograft And A Collagen Stabilizing Intra-Articular Injection To Remediate Cartilage Focal Lesions To Prevent Osteoarthritis, Mark Lewis Mosher

Theses and Dissertations

Osteoarthritis is one of the most common causes of disability in adults in America. It is a progressive and degenerative disease where the articular cartilage is broken down and lost from the surfaces of bones causing chronic pain and swelling in the joints, and currently has no cure. The most commonly osteoarthritis starts from a focal lesion on the cartilage surface, which will expand on the surface and downwards through the thickness of the tissue. The current gold standard for correcting cartilage focal lesions is the osteochondral autograft/allograft transplantation (OAT), which replaces the defect with a fresh osteochondral graft. The …

Oxidized Fibrin Alginate Microbeads To Treat Vascular Calcification, Brittany Nichole Macha

Theses and Dissertations

Calcification is linked to a high prevalence of cardiovascular events and mortality due to arterial stiffness. Stiffening of the arteries in the case of medial calcification is due to hydroxyapatite mineral deposited in the artery thus leading to the loss of elastin. A possibility of removing this rogue mineral along the vessel walls could be the use of osteoclasts. Osteoclasts, a type of osteocyte, have the unique ability to absorb bone in the bone turnover process. It is proposed that in the future, osteoclasts be delivered to the site of mineralization through oxidized alginate-fibrin microbeads. Alginate hydrogels have proven great …

Image-Based Cancer Diagnosis Using Novel Deep Neural Networks, Hosein Barzekar

Theses and Dissertations

Cancer is the major cause of death in many nations. This serious illness can only be effectivelytreated if it is diagnosed early. In contrast, biomedical imaging presents challenges to both clinical institutions and researchers. Physiological anomalies are often characterized by modest modifications in individual cells or tissues, making them difficult to detect visually. Physiological anomalies are often characterized by slight abnormalities in individual cells or tissues, making them difficult to detect visually. Traditionally, anomalies are diagnosed by radiologists and pathologists with extensive training. This procedure, however, demands the participation of professionals and incurs a substantial expense, making the classification of …

Deciphering The Firing Patterns Of Hippocampal Neurons During Sharp-Wave Ripples, Kourosh Maboudi Ashmankamachali

Theses and Dissertations

The hippocampus is essential for learning and memory. Neurons in the rat hippocampus selectively fire when the animal is at specific locations - place fields - within an environment. Place fields corresponding to such place cells tile the entire environment, forming a stable spatial map supporting navigation and planning. Remarkably, the same place cells reactivate together outside of their place fields and in coincidence with sharp-wave ripples (SWRs) - dominant electrical field oscillations (150-250 Hz) in the hippocampus. These offline SWR events frequently occur during quiet wake periods in the middle of exploration and the follow-up slow-wave sleep and are …

Importance Of Light Activation For Plant Cryptochrome And Antibacterial Drug Delivery Strategies, Merfat Ahmed Hammad

Theses and Dissertations

The goal of this project is to investigate the benefits of applying light in different systems. In the first part, the magnetoreception process that occurs in the light activated cryptochrome of Arabidopsis Thaliana was investigated. In the second part, photo-carbon monoxide releasing molecules (photo-CORMs) were investigated for their antibacterial effect to develop biomedical strategies. Overall, this has been achieved in three different studies. The first study investigated if the forward lightdriven reaction is involved in the magnetoreception process or not in cryptochrome (CRY). To accomplish this, the plant seedlings were tested for 90 minutes as follows: 5 minutes in the …

Investigating The Role Of Cryptochrome Activity In Arabidopsis Plant And Blue Light Exposure In Saos-2 Cell-Mediated Mineralization, Maria Nijr Albaqami

Theses and Dissertations

Cryptochromes (CRYs) are flavoproteins that absorb blue light and are associated with the perception of electromagnetic stimuli in a variety of organisms including animals and plants. When exposed to blue light, CRYs undergo flavin redox cycles and form radical pairs intermediates that are assumed to be magnetically sensitive as predicted by the radical-pair hypothesis. However, it is unknown if CRYs fulfill the criteria to act as biological magnetosensors. In the first aim, Arabidopsis thaliana seedlings were exposed to blue light and a time-dependent weak magnetic field at radiofrequency (RF) of 7 MHz as a diagnostic tool to test the radical-pair …

Bioactive Self-Forming Hydrogels For Biomedical Applications, Kirstene Arcuino Gultian Giddings

Theses and Dissertations

Hydrogels are soft biomaterials that feature a wide range of physical and biochemical properties. Although highly versatile, hydrogels typically require an exogeneous input (e.g., light, pH, temperature) to form, and this limits their use to conditions where a catalyst is present. The goal of this dissertation is to expand the use of catalyst-based hydrogels by developing hydrogels with independently tunable properties which gel in situ without external stimuli. This new class of hydrogels was developed by first modifying macromers with norbornene (Nor) or tetrazine (Tet) moieties. Macromers containing Nor or Tet remain liquid when dissolved, and upon mixing self-form into …

Histomechanical Compatibility Of Coronary Artery Bypass Grafts, Colton J. Kostelnik

Theses and Dissertations

Coronary artery disease is a localized form of atherosclerosis that can severely restrict blood flow to the heart often requiring a surgical intervention known as coronary artery bypass grafting (CABG) to reestablish perfusion to this essential circulation. To some extent, the selection of the autograft tissue is at the surgeon’s discretion with factors such as stenosis location and the existing tissue’s pathological state contributing to a choice that could be deterministic in surgical outcomes. Many post-operative complications and premature graft failures originate from graft-target tissue incompatibilities and altered blood flow patterns. We hypothesize that mechanical mismatching between the graft material …

Investigating The Impact Of Endothelial Dysfunction And Aging On Vascular Remodeling Using Mouse Models, Liya Du

Theses and Dissertations

Endothelial dysfunction, characterized by a reduction in the bioavailability of nitric oxide (NO), is a major factor in the initiation and progression of atherosclerosis, an age-related chronic inflammatory process in the arterial wall and the leading cause of mortality and morbidity globally. A better understanding of alterations in vascular structure and function associated with endothelial dysfunction can facilitate the early detection of atherosclerosis and the development of potential pharmaceutical interventions. This study aims to clarify the impact of endothelial dysfunction in conjunction with aging on the microstructure of aortic extracellular matrix (ECM) and to elucidate the relationship between microstructural adaptation …

Effects Of Cell-Cell Signaling On Mesenchymal Stem Cell Mechanosensing And Adaptation To Dynamic Material, Matthew E. Lowe

Theses and Dissertations

The goal of this research is to identify the role of engineered cell-cell signals on how cells sense material properties. Mesenchymal stem cells (MSCs) are adult cells whose behavior is regulated by matrix mechanosensing, which is characterized by stiffness-dependent changes in cell shape and the nuclear localization of mechano-transducer proteins including YAP (Yes-associated Protein). MSC area and nuclear YAP translocation increase with increasing stiffness, and although low levels of N-cadherin-based cell-cell signaling reduce this effect, two fundamental questions remain: (1) do engineered cell-cell signals at higher concentrations further reduce matrix mechanosensing, and (2) does N-cadherin signaling affect MSC adaptation to …

The Role Of Small Gtpases In Regulating Blood-Brain Barrier Mechanotransduction, Brandon Jude Deore

Theses and Dissertations

Fluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the effect of shear on the blood-brain barrier (BBB) have yet to be clarified in cerebral vasculature despite its importance for brain homeostasis.. Neurological symptoms including the formation of microclots, stroke, and other neurological pathologies associated with changes in cerebral blood flow are hallmarks of BBB dysfunction. The in vitro model used in this dissertation is compatible with real-time measurement of barrier function using a transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level …

Bioengineered Scaffolds To Induce Alignment And Promote Axon Regeneration Following Spinal Cord Injury, Kiet Anh Tran

Theses and Dissertations

Scaffolds delivered to injured spinal cords to stimulate axon connectivity often act as a bridge to stimulate regeneration at the injured area, but current approaches lack the permissiveness, topology and mechanics to mimic host tissue properties. This dissertation focuses on bioengineering scaffolds through the means of altering topology in injectables and tuning mechanics in 3D-printed constructs as potential therapies for spinal cord injury repair. A self-assembling peptide scaffold, RADA-16I, is used due to its established permissiveness to axon growth and ability to support vascularization. Immunohistochemistry assays verify that vascularized peptide scaffolds promote axon infiltration, attenuate inflammation and reduce astrogliosis. Furthermore, …

Behavioral And Histological Inflammatory Analysis Of A Single, Mild Traumatic Brain Injury And Repeated Subconcussive Brain Injury Using A Rodent Model., Anna Marie Clay

Theses and Dissertations

Subconcussive (SC) impacts have become a growing concern within the neuroscience community regarding the immediate and long-lasting effects of sports-related injuries. While a single low-level impact, i.e., a subconcussion, may not cause cerebral perturbations, it has been increasingly recognized that repeated SC exposure can induce deleterious effects. Therefore, determining the lower limits of systematic perturbation resulting from multiple SC impacts is of critical importance in expanding our understanding of cerebral vulnerability and recovery. Currently, there is a lack of correlation between a mild traumatic brain injury (mTBI) and repeated SC impacts with respect to injury biomechanics. Moreover, the cumulative threshold …

Python-Based Analysis To Segment Bone And Soft Tissue In A Healing Callus, Roberto Lopez

Theses and Dissertations

The main objective of this study was to produce a Python script that would help facilitate the segmentation process of both bone and soft tissue. The proposed script, in tangent with ImageJ and Mimics, was successful in producing viable results when the bone and soft tissue sample was placed near hydroxyapatite (HA) phantoms during the image acquisition process. It was important to acquire both the HA phantoms and the sample within the same image sequence as the script functioned by analyzing the statistical distribution of the different HA regions to locate the most ideal thresholding ranges to determine the bone …

Ethanol-Induced Impacts On Nervous System Development And Dopamine Transporter Characterization In Schmidtea Mediterranea Planaria, Brennen Covely

Theses and Dissertations

Fetal alcohol spectrum disorders (FASD) are diagnosed in 2-5% of newborns, but the biology underlying FASD is poorly understood and challenging to study with existing model organisms. A new model for FASD research is Schmidtea mediterranea (Smed) planaria. Smed have a remarkable ability to regenerate their central nervous system (CNS), and possess a well-studied, simple genome. Previous studies have shown that ethanol exposure delays this regeneration, yet this relationship is not fully understood. Here, we show that alcohol exposure affects Smed in a dose-dependent manner, eliciting characteristic withdrawal-like behaviors and impacting cognitive function. Interestingly, prior exposure does not alter subsequent …

Optimizing Left Ventricular Assist Device Hemodynamics Via Patient Specific Computational Analysis, Jasmine Josefina Martinez

Theses and Dissertations

The best treatment for patients with end stage heart failure is a heart transplant but given the scarcity of donor hearts, a promising alternative treatment has become left ventricular assist devices (LVAD). However, complications such as right heart failure, stroke, and adverse hemodynamic outcomes continue to occur. This thesis will cover investigations into continuous flow LVAD treatment optimization techniques to improve patient outcomes. Optimization techniques explored include an in-house developed optimization algorithm that is completed in three phases on a computational lumped parameter model that is representative of the cardiovascular system using an electrical circuit analogy. This three-phase optimization technique …

The Effect Of Pulsed Field Dc Electrophoresis And Field Amplified Sample Stacking On The Microchip Electrophoretic Separation Of Organic Dyes, Travis Geoffrey Stewart

Theses and Dissertations

The utility of field amplified sample stacking and pulsed field electrophoresis toward improving electrophoretic outcomes was studied with regards to the electrophoretic separation of three organic dyes rhodamine B, 2’,7’-dichlorofluorescein, and fluorescein salt in microchip electrophoresis conditions. In this study, there were four experimental groups: nonstacking nonpulsed, nonstacking pulsed, sample stacking nonpulsed, and sample stacking pulsed.

Electrophoretic outcomes were evaluated by examining the electrophoretic separations under an epifluoresence detection method, plotting the signal intensities vs. time, and comparing separation resolutions and signal-to-noise ratios between experimental groups. From this it was shown that sample stacking nonpulsed conditions yielded the best outcome …

Neurochemical, Molecular, And Behavioral Effects Of Intranasal Insulin, Jennifer Marie Erichsen

Theses and Dissertations

Age-related cognitive decline (ARCD) is one of the most dreaded aspects of growing old and a public health concern. Unfortunately, there is currently no treatment that effectively ameliorates ARCD. In recent decades, intranasal insulin (INI) has demonstrated promising memory enhancements for rodents and individuals with Alzheimer’s disease, both in basic science research laboratories and multi-center clinical trials. Other studies have shown INI improves memory and cognition in healthy rodents and humans, indicating that INI may hold promise as a successful ARCD therapeutic. However, there is a glaring lack of evidence regarding how INI produces these effects. The goal of these …

Long Non-Coding Rna Pvt1 – An Exploratory Study In Ovarian And Endometrial Cancer, Kevin Tabury

Theses and Dissertations

Gynecological cancers, ovarian and endometrial cancer, are still leading causes of cancer-related death in women worldwide. Early detection methods as well as treatment resistance remain a challenge. Long non-coding RNAs (lncRNAs) are emerging as therapeutic targets with diagnostic and prognostic potential with lncRNA PVT1 being one of them.

Here I test and demonstrate the role of PVT1 in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer and has predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to cellular stress, particularly loss …

Electro-Mechanical Data Fusion For Heart Health Monitoring, Kemal Yakut

Theses and Dissertations

Heart disease is a major public health problem and one of the leading causes of death worldwide. Therefore, cardiac monitoring is of great importance for the early detection and prevention of adverse conditions. Recently, there has been extensive research interest in long-term, continuous, and non-invasive cardiac monitoring using wearable technology. Here we introduce a wearable device for monitoring heart health. This prototype consists of three sensors to monitor electrocardiogram (ECG), phonocardiogram (PCG), and seismocardiogram (SCG) signals, integrated with a microcontroller module with Bluetooth wireless connectivity. We also created a custom printed circuit board (PCB) to integrate all the sensors into …

Biomimetic Strategies To Control Therapeutic Release From Novel Dna Nanoparticles, Robert J. Mosley

Theses and Dissertations

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the …

Electromechanical Fatigue Properties Of Dielectric Elastomer Stretch Sensors Under Orthopaedic Loading Conditions, Andrea Karen Persons

Theses and Dissertations

Fatigue testing of stretch sensors often focuses on high amplitude, low-cycle fatigue (LCF) behavior; however, when used for orthopaedic, athletic, or ergonomic assessments, stretch sensors are subjected to low amplitude, high-cycle fatigue (HCF) conditions. As an added layer of complexity, the fatigue testing of stretch sensors is not only focused on the life of the material comprising the sensor, but also on the reliability of the signal produced during the extension and relaxation of the sensor. Research into the development of a smart sock that can be used to measure the range of motion (ROM) of the ankle joint during …

Effects Of Orthopedic Implant And Host Bone Properties On Stress-Shielding Induced Osteopenia, Scott Jason Jan Baskerville

Theses and Dissertations

Stress shielding is a term commonly used in literature to describe a bone density reducing phenomenon which occurs due to long-term exposure of bone tissue to sub-homeostatic levels of mechanical stimuli. A number of mechanobiological models ranging in complexity and purpose have been developed with the general overall intent of predicting bone remodeling behavior under a set of prescribed conditions. A previously developed heuristic model is expanded in the present work through model calibration with physiological data and the development of a reduced bone-implant-construct (BIC) mechanical model configurable for patient factors such as age, gender, and associated bone properties. The …

Computer Vision And Machine Learning Applications In Cellular Images And Clinical Data, Guochang Ye

Theses and Dissertations

With the progressive development of artificial intelligence (AI), automated analysis has been explored for substituting tedious manual methods in cellular image analysis. Additionally, medical information not included in the conventional statistical methods is now being reconsidered with AI-based personalized medicine. The adaptivity and flexibility of AI ensure its efficiency and accuracy. In this work, computer vision and machine learning (ML) methods under the scope of AI are explicitly investigated and applied to cellular images and clinical data for cytological analysis and to provide diagnosis-based assistance/predictions. Firstly, novel computer vision algorithms achieve cell detection and differentiation estimation on phase-contact microscopic images …

Full-Body Biomechanical Characterization Of Children With Hypermobile Ehlers-Danlos Syndrome During Gait And Activities Of Daily Living, Anahita Alahmoradiqashqai

Theses and Dissertations

Hypermobile Ehlers-Danlos syndrome (hEDS) is an inherited connective tissue disorder, often under-diagnosed, and presenting with frequent chronic pain and severe musculoskeletal symptoms that can drastically reduce the quality of life during one’s life span. While there are limited quantitative approaches in the literature on adult movements, the biomechanics of movements during activities of daily living (ADLs) in children have not been investigated comprehensively. Therefore, the primary purpose of this dissertation was to characterize the biomechanics of the musculoskeletal system and investigate the biomechanics of hEDS by quantifying joint dynamics and muscle activations during ADLs and gait in the pediatric population. …

Cellular Migration As A Function Of Magnetic Field Intervention, Amy Marie Vecheck

Theses and Dissertations

This work aims to assess cellular migration in three-dimensional structures as a function of Zeeman resonance. By using Zeeman resonance to initialize intersystem crossing of electrons, also known as the Radical Pair Mechanism, bioenergetics processes would be modulated. Processes such as oxygen consumption rate and extracellular acidification rate are indicative of cellular respiration and glycolysis and can be altered based on the orientation of the magnetic field applied: parallel and perpendicular, respectively. This study focused on the parallel orientation and looked to used Zeeman resonance to increase flavin adenosine dinucleotide, which results in preventing the breakdown of F-actin. Cellular viability …

Influence Of Mouthguard Design On Sports Performance And Injury Prevention, Mohammad Ahmed

Theses and Dissertations

Contact sports are associated with some invisible injuries after the incident when symptoms do not appear until weeks after. This can be dangerous as players may continue to engage in the sport and risk further injury. Athletic mouthguards are used to reduce the risk of injury, but there is insufficient data to quantify the effectiveness of mouthguard design on sports performance and injury prevention. In this work, the thickness and material selection of the mouthguard design were characterized in terms of airway resistance, electromyography muscle activation, and energy absorption. First, the effect of thickness on the condyle and temporal bone …

Bio-Ionic Liquid Functionalized Hydrogels Towards Smart Tissue Regeneration, Vaishali Krishnadoss

Theses and Dissertations

A blend of scaffolds, biologically active molecules, and cells are required to assemble functional constructs to repair and regenerate damaged tissue or organ via tissue engineering. The scaffold supports cell growth and proliferation and acts as a medium for diverse cellular activities. Even though hydrogel's high-water content and flexible nature make it a pronounced applicant as a scaffold, they exhibit significant technical limitations such as the absence of cell-binding motifs, lack of oxygen, conductivity, adhesive properties, growth of cells in a 3-dimensional (3D) microenvironment. In this thesis, a novel material platform is evaluated and studied to address the concerns mentioned …

Image Processing Algorithms For Detection Of Anomalies In Orthopedic Surgery Implants, Alexander William Wiese

Theses and Dissertations

Orthopedic implant procedures for hip implants are performed on 300,000 patients annually in the United States, with 22.3 million procedures worldwide. While most such operations are successfully performed to relieve pain and restore joint function for the duration of the patient's life, advances in medicine have enabled patients to outlive the life of their implant, increasing the likelihood of implant failure. There is significant advantage to the patient, the surgeon, and the medical community in early detection of implant failures.The research work presented in this thesis demonstrates a non-invasive digital image processing technique for the automated detection of specific arthroplasty …

The Submission Of A Section 513(G) Request For Information, Morgan Ashley Lano

Theses and Dissertations

The Food and Drug Administration designates all medical devices into one of three general classes contingent on their intended use, indications for use, and potential risk to the user. This classification dictates the further path the device must take to be approved for the commercial market. Section 513(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360c(g)) is submitted in order to gain the agency’s unofficial classification and suggested regulatory requirements. The Coagulation Companion (MicroVide) is a device designed to fluorescently quantify a key enzyme involved in the coagulation cascade, plasmin, in pediatric patients. clot formation and degradation …