Biomedical Engineering and Bioengineering Commons^™

3d Bioprinted Coaxial Tubule Optimization For Human Aortic Endothelial Cell Growth, Ilse Gabriela Perez Garcia

Theses and Dissertations

This paper introduces a research study of printing parameter optimization of extruded, cell-laden, 3D bioprinted coaxial tubules, as well as cell interaction observations. Optimization of printing parameters seeks to reduce variability of the tubules’ inner and outer diameters. The tubules were manufactured from a 0.4% Collagen I - 1.6% NaC6H7O6 (Sodium Alginate) bioink, that reaches gelation through interaction with a 3.2% CaCl2 (Calcium Chloride) solution. The bioinks were extruded through a dual syringe pump mechanism connected to a coaxial nozzle, which is mounted on an adapted 3D FDM (Fused Deposition …

Demonstrating Feasibility Of Ultrasound-Sensitive Microbubbles Delivery To Treat Disruptions In The Blood Brain Barrier Endothelium, Rubens Jourdain

Theses and Dissertations

Vascular cognitive impairment and dementia (VCID) is one of the main causes of dementia. VCID is caused by age and other genetic factors that lead to disruptions in the blood brain barrier (BBB) and allow blood components to enter the brain. The currently available treatments of VCID include opening the BBB with high-frequency-ultrasound to deliver drugs to the brain. However, this only treats the already developed disease. Consequently, we developed a new drug delivery system whose goal is to restore the brain capillary endothelial cells (BCEC) lining the blood vessel. The objective of this study was to demonstrate the feasibility …

Effect Of Storage Time And Temperature On Aggregation Of Alzheimer's Disease Amyloid-Β Protein, Amy Veihdeffer

Theses and Dissertations

Amyloid-β protein (Aβ) is widely studied due to its key role in Alzheimer’s disease (AD) pathology. One characteristic of patients suffering from AD is the deposition of amyloid plaques comprised of Aβ aggregates, which are associated with synapse damage. Thus, studying Aβ aggregation and aggregation inhibition may provide pathological and therapeutic insights. Aggregation of Aβ is a nucleation dependent process that may be influenced by the presence of pre-formed Aβ aggregate seeds that can facilitate formation of protein aggregates. These seeds may appear during preparation or storage of monomer, posing impact on experiments that study the aggregation process and the …

Vascular Calcification In A Mouse Model Of Chronic Kidney Disease And In Human Peripheral Arterial Disease, Breanna Pederson

Theses and Dissertations

Vascular calcification is a process in which calcium and phosphate crystallize to form hydroxyapatite in the extracellular matrix of blood vessels. There are two forms of arterial calcification: intimal and medial, which occur via different etiologies. Intimal calcification is associated with atherosclerosis and occurs in the layer of endothelial cells adjacent to the artery lumen. Medial arterial calcification (MAC) is independent of atherosclerosis and occurs in the middle, muscular layer of the artery. MAC is strongly associated with aging, diabetes mellitus, and chronic kidney disease (CKD). MAC is frequently in patients with peripheral arterial disease (PAD). Most studies to date …

Development Of A Haptic System For Robot-Assisted Femur Fracture Surgery, Fayez H. Alruwaili

Theses and Dissertations

Robot-assisted surgery has emerged within the field of surgical technology, driven by the need for greater accuracy and speed in the ongoing evolution of healthcare. This advancement has influenced numerous areas requiring enhancements to achieve optimal surgical results. However, surgical robotics tends to lack the surgeon’s connection to the operation, creating a gap in the intuitive skill set required for successful operations. The gap is seen through the lack of sense of touch, which may result in tissue damage and additional injury when the robot interacts with the patient. Furthermore, challenges faced during femur fracture surgery have positioned robot-assisted surgery …

Injectable Hydrogels That Can Measure Radiation At Body Temperature, Daniel Joseph Ball

Theses and Dissertations

Hydrogel-based radiation dosimeters are used to calibrate and validate radiation delivered by linear accelerators used in radiotherapy. Specifically, Fricke hydrogel-based dosimeters containing ferrous ion complexes oxidize upon exposure to radiation, leading to a change in optical density that can be measured via a color change in a photometric reagent. While gelatin-based Fricke hydrogels are routinely used to measure radiation, these hydrogels are unstable at body temperature, and it is currently not possible to noninvasively measure radiation dose inside a patient. This study reports the synthesis and characterization of self-forming hydrogels containing Fricke components that are stable at body temperature. The …

Nanofiber-Hydrogel Composite Scaffold Fabrication Methods For Peripheral Nerve Regeneration, Jacob Lee Carter

Theses and Dissertations

Nerve graft conduits (NGCs) are a rapidly advancing field for treating peripheral nerve injuries that aim to guide the growth of regenerating axons across damaged gaps. A more effective NGC can be manufactured by combining the use of nanofibers to act as guidewires within a 3-D hydrogel that imitates the extracellular matrix of nerve tissue. Several methods have been developed to embed aligned nanofibers in an ordered architecture within a hydrogel matrix. The first method involves layer-by-layer additive manufacturing to create NGCs with rows of polycaprolactone (PCL) nanofibers surrounded by a gelatin methacrylate (GelMe) hydrogel in a 3-D structure. A …

A Novel Perfused Contusion Spinal Cord Injury Model To Assess Rapid Mechanical Properties Changes After Blood Spinal Cord Barrier Breakdown, Laura De Marchi

Theses and Dissertations

Blood-spinal cord barrier (BSCB) disruption exacerbates the tissue damage caused by spinal cord injury (SCI), but the mechanisms and dynamics of how the barrier breakdown affects the mechanical properties of the tissue remain unclear. The perfused bovine ex vivo indentation injury model described here represents a new platform to investigate the short-term effects of altered blood flow and vascular permeability following traumatic spinal cord injury. Our results indicate that injured cords exhibit changes to bulk perfusion, as evidenced by laser speckle contrast imaging, in addition to decreased barrier function shortly after injury. Indentation tests that simultaneously simulate a crush injury …

Investigating The Effects Of Calcitonin Gene Related Peptide On Heart Failure And The Gut Microbiome, Talia Charlotte Kepniss

Theses and Dissertations

Heart failure affects millions of people worldwide with current available treatments that are limited in their efficacy. The financial burden for care of those with heart failure is over 20 billion dollars in the US alone. Calcitonin gene related peptide has demonstrated cardioprotective and powerful vasodilator effects. In this study our objective is to prevent the onset of heart failure and treat early stages of heart failure with injections of calcitonin gene related peptide in C57BL/6 mice. In order to model heart failure, experimental mice underwent a transverse aortic constriction surgery. Echocardiograms and fecal collections were completed to observe changes …

Enabling Novel Nanopore Sensing Approaches For Personalized Medicine Through Chemical Modifications To Analytes, Zehui Zhang

Theses and Dissertations

Nanopore sensors have garnered significant attention recently, not only for their groundbreaking advancements in single-molecule DNA sequencing but also for their diverse applications in stochastic sensing, single-molecule chemistry, and protein unfolding. The interaction of single molecules with the nanopore sensing interface leads to characteristic ionic current modulations, reflecting the composition, charge, distribution, structure, and sequence of the translocating molecule. With the electrical resistive pulse nanopore sensing, its single-molecule sensitivity and specificity have opened doors to numerous potential applications in personalized medicine. I will discuss recent advancements in the sensitivity and specificity of personalized medicine using nanopore sensors, focusing on proteomic …

Innovative 4d Printing Of Biomimetic Collagen-Tcp Scaffolds For Bone Regeneration, Karly Morgan Liebendorfer

Theses and Dissertations

Bone tissue engineering (BTE) is a promising alternative approach to autografts and allografts when treating various bone diseases and disorders. BTE enables the fabrication of biocompatible, biomimetic, and osteo-stimulating constructs for the repair and regeneration of damaged bone tissue. The native bone environment primarily consists of anisotropic type 1 collagen (organic) and hydroxyapatite nanocrystals (inorganic). Composite biomimetic scaffolds fabricated by combining collagen with bioceramics have shown immense promise for BTE applications. Prior work has reported on different biofabrication methods to synthesize collagen-based composite scaffolds for use in BTE applications. However, to date, a customizable 3D composite scaffold that resembles the …

Patient-Specific Hemodynamic Modeling For Optimizing Left Ventricular Assist Device And Right Heart Health, Holly Felice Grant

Theses and Dissertations

LVAD speed optimization is essential for efficient LVAD therapy and to minimize complications. However, the ideal LVAD speed is unknown and must be tailored for each patient. The interplay between the LVAD, systemic, and pulmonary circulations is critical and should be considered during optimization. A computational hemodynamic model that can be tailored for each patient may provide clinicians with useful guidance and reduce the need for repeated invasive studies. This study sought to customize and evaluate a patient-specific LVAD hemodynamic optimization model.

We conducted a retrospective analysis on 25 patients implanted with HM3 and who underwent right heart catheterization (RHC) …

Chemotherapy Drug Release From Hollow Core Polyethyleneimine Nanoparticles, Brian Boyle

Theses and Dissertations

Novel anticancer delivery vehicles are arising from engineered nanostructured materials. This work involved the synthesis, characterization, and release of novel hollow core polymeric nanoparticles (HCPNPs) for controlled drug delivery. Polyethyleneimine (PEI) was bound to AuNPs, forming polymer-shell nanoparticles with dissolution of the gold core via iodine forming HCPNPs with drug intercalated DNA bound to the surface. A high density (85 molecules/particle) of DNA intercalated with daunorubicin was conjugated. Particles were spherical with an average diameter of 105.7 ± 17.3 nm and zeta potential of 20.4 ± 3.54 mV. We hypothesize the DNA backbone electrostatically condensed to the primary amines on …

Shape Memory Alloy Capsule Micropump For Drug Delivery Applications, Youssef Mohamed Kotb

Theses and Dissertations

Implantable drug delivery devices have many benefits over traditional drug administration techniques and have attracted a lot of attention in recent years. By delivering the medication directly to the tissue, they enable the use of larger localized concentrations, enhancing the efficacy of the treatment. Passive-release drug delivery systems, one of the various ways to provide medication, are great inventions. However, they cannot dispense the medication on demand since they are nonprogrammable. Therefore, active actuators are more advantageous in delivery applications. Smart material actuators, however, have greatly increased in popularity for manufacturing wearable and implantable micropumps due to their high energy …

Transforming Orthopedic Surgery: Autonomous Image-Guided Techniques For Femur Fracture Robotic Surgery, Marzieh Sadat Saeedi-Hosseiny

Theses and Dissertations

Long-bone fractures, particularly femur fractures, are prevalent and necessitate surgical intervention due to traumatic forces. Manual reduction procedures pose challenges, including excessive traction forces and reliance on limited X-ray imaging, resulting in malalignment-related complications and repeated surgeries. Current methods for femur fracture reduction are prone to inaccuracies, prolonged surgical times, and postoperative complications. This research introduces image-guided methods to automate a surgical robotic system, Robossis, to enhance femur alignment accuracy, reduce procedure times, and improve patient outcomes. To address these challenges, a marker-based approach utilizing a few X-ray images is developed to detect the spatial relative position of the femur …

Design And Development Of Contactless Capacitive Coupled Electrodes For Cardiovascular Signal Acquisition, Ramya Lakshmi Vs

Theses and Dissertations

In biosignal acquisition and physiological monitoring, developing advanced electrode technologies is crucial in enhancing signal quality, minimizing interference, and improving overall reliability. One such innovative approach is the utilization of capacitive-coupled electrodes, a cutting-edge solution that addresses some of the challenges associated with traditional electrodes in biosignal recording.

Capacitive-based sensors have become prominent in physiological signal measurement over the past decade. The electric field from the external affects both the human body and the electrode. The primary aim while designing the capacitive electrode is to maximize the signal-to-noise ratio. Hence, we introduce shielding and guarding techniques to improve the signal-to-noise …

Analysis And Evaluation Of Different Transformer Architectures For The Protein Sequence Representation And The Corresponding Hypothetical Applications, Mary Mao

Theses and Dissertations

This project is to investigate and assess several Transformer topologies for the modeling of protein sequences and their corresponding uses. Each major model for the protein sequence representations is inspected with its mathematical theory and analyzed for the different performance of the models with various validation repositories.

Photo-Carbon Monoxide Releasing Molecules For Antibacterial Benefits In Vascular Grafts, Beste Caner

Theses and Dissertations

Globally, the annual hemodialysis procedures surpass 1.5 million, emphasizing the vital role of reliable vascular access methods. However, common challenges like access infections and clot-induced blood flow reduction necessitate innovative solutions. This study delved into the potential therapeutic role of carbon monoxide (CO) and its effects on both endothelialization and non-pathogenic bacteria causing infections. The primary focus was evaluating the impact of loading different concentrations of carbon monoxide-releasing molecules (CORMs), specifically CORM diketone 4 (DK4), within 2D spin-coated films on cultured E. coli and endothelial cells. Initial assessments of CO release kinetics from DK4-loaded films demonstrated that the 10% condition …

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

Theses and Dissertations

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

Controlled Delivery Of Peptide And Gasotransmitter For Promoting Vascular Endothelialization, Shirin Changizi

Theses and Dissertations

Endothelial cells (ECs) are vital for maintaining proper vascular function and regulating processes such as hemostasis and inflammation. Disruption of endothelial cells integrity can lead to several pathological conditions, including coronary artery disease, vascular cognitive impairment, and dementia (VCID). Alterations in ECs distribution may lead to compromised blood-brain barrier (BBB) function, facilitating the passage of blood components and contributing to conditions such as Alzheimer's disease. Additionally, disruptions in ECs function can lead to early-stage thrombosis and intimal hyperplasia, resulting in graft failure in small-diameter (

This study aimed to develop innovative approaches for drug delivery to the BBB and TEVGs …

Microwave Imaging Technique For Breast Cancer Detection, Nure Alam Chowdhury

Theses and Dissertations

Breast cancer is a global problem, and it is inevitable to detect cancerous cells at early stages. In recent years, microwave imaging technology has been widely applied in biomedical applications for its non-ionizing radiation. In this study, we design a micro-strip patch antenna with an inverted T-type notch in the partial ground to detect tumor cells inside the human breast. The size of the current antenna is small enough (18 mm × 21 mm × 1.6 mm) to distribute around the breast phantom. The operating frequency has been observed from 6–14 GHz with a minimum return loss of −61.18 dB …

Tunable Dual-Phase Dual-Drug Delivery System Using A Plga Microparticle/Pva Hydrogel Composite, Timothy John Eck

Theses and Dissertations

Current drug-eluting coatings have demonstrated controlled long-term, sustained release but have only tried to mitigate short-term burst release as a negative side effect. For applications like wound healing, there is a need for a drug-eluting coating which is adjustable in both short- and long-term release, independent of each other. We present a tunable dual-phase dual-drug delivery coating composed of drug-loaded polymer microparticles and drug-loaded hydrogel which can control short term and long term release individually in this study. This coating was created using lidocaine and dexamethasone encapsulated in poly(D,L-lactide-co-glycolide) particles combined with lidocaine- and dexamethasone-loaded poly(vinyl alcohol) hydrogel. Hydrogel drug …

Development Of 3d Printed Anatomically Equivalent Thermoplastic Polyurethane Conduits For Peripheral Nerve Regeneration, Allen Zennifer M

Theses and Dissertations

Three-dimensional (3D) printing is an emerging tool for creating patient-specific tissue constructs analogous to the native tissue microarchitecture. In this study, anatomically equivalent 3D nerve conduits were developed using thermoplastic polyurethane (TPU) by combining reverse engineering and material extrusion (i.e., fused deposition modelling) technique.

Printing parameters were optimized to fabricate nerve-equivalent TPU constructs. The TPU constructs printed with different infill densities supported the adhesion, proliferation, and gene expression of neuronal cells. Subcutaneous implantation of the TPU constructs for three months in rats showed neovascularization with negligible local tissue inflammatory reactions and was classified as a non-irritant biomaterial as per ISO …

Deploying Field-Capable Genome Sequencing: Human Performance Considerations Under Various Personal Protective Equipment Ensembles, Steven A. Torres

Theses and Dissertations

Field-portable genome sequencing enhances the Department of Defense's strategy for detecting biological threats, particularly in resource-limited environments. While current field-capable detection methods are effective, challenges in identifying emerging threats pose risks to personnel safety. As biotechnological advancements like portable nanopore genome sequencing can advance biological detection capabilities, the viability of conducting laboratory tasks under Mission-Oriented Protective Posture (MOPP) ensembles lacks sufficient data. This research assesses the effectiveness of tools like pipettes, centrifuges, vortexes, and nanopore sequencing within a MOPP ensemble. Novice participants were utilized to explore the extension of this capability, and they completed tasks in three conditions: Fatigues, Laboratory …

Mri Image Regression Cnn For Bone Marrow Lesion Volume Prediction, Kevin Yanagisawa

Theses and Dissertations

Bone marrow lesions (BMLs), occurs from fluid build up in the soft tissues inside your bone. This can be seen on magnetic resonance imaging (MRI) scans and is characterized by excess water signals in the bone marrow space. This disease is commonly caused by osteoarthritis (OA), a degenerative join disease where tissues within the joint breakdown over time [1]. These BMLs are an emerging target for OA, as they are commonly related to pain and worsening of the diseased area until surgical intervention is required [2]–[4]. In order to assess the BMLs, MRIs were utilized as input into a regression …

Performance Analysis And Evaluation Of Image Processing Techniques, Dcnn And Bsn Model For Detection And Classification Of Diabetic Retinopathy, Sudha S

Theses and Dissertations

Diabetes is a disorder that arises when blood sugar level increases. Insufficient secretion of insulin hormone is the ground for the evolution of diabetes, and it affects most of the critical organs in our body. Diabetes causes leakage of blood in the retinal blood vessels, inducing an eye disease, Diabetic Retinopathy (DR). The visual identification of micro features in fundus images makes the clinicians complex and challenging tasks. Therefore, timely diagnosis and proper treatment can prevent eye blindness. This research is proposed to identify and classify diabetic retinopathy using an Image Processing technique, Deep Convolutional Neural Network (DCNN), Biological Sensor …

Cancer Treatment By Targeting Hdac4 Translocation Induced By Microsecond Pulsed Electric Field Exposure: Mechanistic Insights Through Kinases And Phosphatases, Zahra Safaei

Theses and Dissertations

Epigenetic modifications, arising from sub-cellular shifts in histone deacetylase (HDAC) activity and localization, present promising strategies for diverse cancer treatments. HDACs, enzymes responsible for post-translational histone modifications, induce these epigenetic changes by removing acetyl groups from ε-N-acetyl-lysine residues on histones, thereby suppressing gene transcription. Within the HDAC group, class IIa HDACs are notable for their responsiveness to extracellular signals, bridging the gap between external stimuli, plasma membrane, and genome through nuclear-cytoplasmic translocation. This localization offers two significant mechanisms for cancer treatment: nuclear accumulation of HDACs represses oncogenic transcription factors, such as myocyte-specific enhancer factor 2C (MEF2C), triggering various cell death …

Development Of A Xenograft For Annular Repair Using Pulsed Electric Field Exposures For Enhanced Decellularization, Prince Mensah Kwaku Atsu

Theses and Dissertations

Severe back injuries and chronic pain necessitate surgical replacement of damaged intervertebral disc (IVD) cartilage in advanced disease stages. Bovine IVD tissue has been exposed to an upper threshold pulsed electric field (PEF) dose, causing cell death without thermal damage to the tissue. Subsequent PEF exposures at lower magnitudes have accelerated the removal of immunogenic biomolecules though electrokinetic extraction using optimized aqueous solutions. This approach yields a natural scaffold, ready for biocompatibility and mechanical strength assessment. The effects of microsecond pulsed electric fields (µsPEF) on primary bovine AF fibroblast-like cells have been characterized in vitro. PEFs of 10 and 100 …

Insights Into The Characterization And Degradation Of Electrospun Polycaprolactone Scaffolds For Tissue Engineering Applications, Caleb B. Wells

Theses and Dissertations

Electrospun polymeric biodegradable scaffolds are essential in tissue engineering, particularly for Engineered Tissue Vascular Grafts (ETVGs), which promise advancements in treating coronary artery disease, peripheral arterial disease, congenital cardiovascular defects, and renal disease. These scaffolds present a solution to issues with autologous graft availability and durability. While large-diameter grafts in low-pressure environments have seen success, small-diameter grafts in high-flow scenarios remain challenging. Understanding polymeric scaffold degradation and behavior during incubation, especially under dynamic mechanical loading, is vital for clinical translation of small-caliber ETVGs.

This research focuses on characterizing the mechanical and microstructural properties of electrospun polycaprolactone (PCL) scaffolds and their …

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

Theses and Dissertations

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