Biomedical Engineering and Bioengineering Commons^™

Rational Design Of Rama-Labeled Nanoparticles For A Dual-Modaility, Light Scattering Immunoassay On A Polystyrene Substrate, Nathan D. Israelsen, Donald Wooley, Cynthia Hanson, Elizabeth Vargis

Biological Engineering Faculty Publications

Background: Surface-enhanced Raman scattering (SERS) is a powerful light scattering technique that can be used for sensitive immunoassay development and cell labeling. A major obstacle to using SERS is the complexity of fabricating SERS probes since they require nanoscale characterization and optical uniformity. The light scattering response of SERS probes may also be modulated by the substrate used for SERS analysis. A typical SERS substrate such as quartz can be expensive. Polystyrene is a cheaper substrate option but can decrease the SERS response due to interfering Raman emission peaks and high background fluorescence. The goal of this research is to …

Bioactive Poly(Beta-Amino Ester) Biomaterials For Treatment Of Infection And Oxidative Stress, Andrew L. Lakes

Theses and Dissertations--Chemical and Materials Engineering

Polymers have deep roots as drug delivery tools, and are widely used in clinical to private settings. Currently, however, numerous traditional therapies exist which may be improved through use of polymeric biomaterials. Through our work with infectious and oxidative stress disease prevention and treatment, we aimed to develop application driven, enhanced therapies utilizing new classes of polymers synthesized in-house. Applying biodegradable poly(β-amino ester) (PBAE) polymers, covalent-addition of bioactive substrates to these PBAEs avoided certain pitfalls of free-loaded and non-degradable drug delivery systems. Further, through variation of polymer ingredients and conditions, we were able to tune degradation rates, release profiles, cellular …

Synthesis And Characterization Of Antioxidant Conjugated Poly(Βeta-Amino Ester) Micro/Nanogels For The Suppression Of Oxidative Stress, Prachi Gupta

Theses and Dissertations--Chemical and Materials Engineering

Oxidative stress is a pathophysiological condition defined by an increased production of reactive oxygen species (ROS), which can result in the growth arrest of cells followed by cell disintegration or necrosis. A number of small molecule antioxidants (e.g. curcumin, quercetin and resveratrol) are capable of directly scavenging ROS, thereby short-circuiting the self-propagating oxidative stress state. However, poor solubility and rapid 1^st pass metabolism results in overall low bioavailability and acts as a barrier for its use as a drug to suppress oxidative stress efficiently.

To overcome this limitation, these small molecule antioxidants were covalently conjugated into poly(β-amino ester) (PβAE) …

Modeling Early Stage Bone Regeneration With Biomimetic Electrospun Fibrinogen Nanofibers And Adipose-Derived Mesenchymal Stem Cells, Michael P. Francis, Yas M. Moghaddam-White, Patrick C. Sachs, Matthew J. Beckman, Stephen M. Chen, Gary L. Bowlin, Lynne W. Elmore, Shawn E. Holt

School of Medical Diagnostics & Translational Sciences Publications

The key events of the earliest stages of bone regeneration have been described in vivo although not yet modeled in an in vitro environment, where mechanistic cell-matrix-growth factor interactions can be more effectively studied. Here, we explore an early-stage bone regeneration model where the ability of electrospun fibrinogen (Fg) nanofibers to regulate osteoblastogenesis between distinct mesenchymal stem cells populations is assessed. Electrospun scaffolds of Fg, polydioxanone (PDO), and a Fg:PDO blend were seeded with adipose-derived mesenchymal stem cells (ASCs) and grown for 7-21 days in osteogenic differentiation media or control growth media. Scaffolds were analyzed weekly for histologic and molecular …

Accessible Bioprinting: Adaptation Of A Low-Cost 3d-Printer For Precise Cell Placement And Stem Cell Differentiation, John A. Reid, Peter A. Mollica, Garett D. Johnson, Roy C. Ogle, Robert D. Bruno, Patrick C. Sachs

School of Medical Diagnostics & Translational Sciences Publications

The precision and repeatability offered by computer-aided design and computer-numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive 'off-the-shelf' commercially available 3D printer. We also demonstrate via goal based …

Fluoroscopic System For Assessment Of In Vivo Hindfoot Kinematics During Gait: Control Data And Applications In Osteogenesis Imperfecta, Ben Mchenry, Jason Long, Peter Smith, Haluk Altiok, Gerald F. Harris

Biomedical Engineering Faculty Research and Publications

No abstract provided.

Categorizing Fetal Heart Rate Variability With And Without Visual Aids, Amanda J. Ashdown, Mark W. Scerbo, Lee A. Belfore Ii, Stephen S. Davis, Alfred Z. Abuhamad

Psychology Faculty Publications

Objective This study examined the ability of clinicians to correctly categorize images of fetal heart rate (FHR) variability with and without the use of exemplars.

Study Design A sample of 33 labor and delivery clinicians inspected static FHR images and categorized them into one of four categories defined by the National Institute of Child Health and Human Development (NICHD) based on the amount of variability within absent, minimal, moderate, or marked ranges. Participants took part in three conditions: two in which they used exemplars representing FHR variability near the center or near the boundaries of each range, and a third …

A Software Application For Cardiac-Gated Computerized Tomography Scanning, Stephen Caldwell, Trevor Engelsman

Williams Honors College, Honors Research Projects

Computerized tomography (CT) scans are a common clinical imaging procedure used worldwide. Operating in the X-Ray spectrum, these machines rotate scanners around a stationary body in order to compile two-dimensional images into a unified three-dimensional image. With adjustment to scan frequency and intensity, internal features such as muscles, organs, and tendons can easily be viewed. However, the heart has long evaded CT use due to its near-constant motion. Recently, cardiac-gated scans have entered the market as a technique to image the heart at a specific moment in time when it is nearly still - the quiescent period. Occurring during rapid …

Characterization Of Fibrin Matrix Incorporated Electrospun Polycaprolactone Scaffold, Cho Yi Wong

Theses and Dissertations

Specific objective: Guided tissue regeneration (GTR) aims to regenerate the lost attachment apparatus caused by periodontal disease through the use of a barrier membrane. For the GTR procedures to be successful, barrier membranes are required to be present at the surgical site for an extended period of time (weeks to months). Synthetic membranes have the advantage of prolonged presence in a wound site; however, they do not actively contribute to wound healing. Biologic membranes are recognized by the host tissue and participate in wound healing but have the disadvantage of early resorption. Therefore, the goal of this study is …

The Protective Role Of Mlcp-Mediated Erm Dephosphorylation In Endotoxin-Induced Lung Injury In Vitro And In Vivo, Anita Kovacs-Kasa, Boris A. Gorshkov, Kyung-Mi Kim, Sanjiv Kumar, Stephen M. Black, David J. Fulton, Christiana Dimitropoulou, John D. Catravas, Alexander D. Verin

Bioelectrics Publications

The goal of this study was to investigate the role of MLC phosphatase (MLCP) in a LPS model of acute lung injury (ALI). We demonstrate that ectopic expression of a constitutively-active (C/A) MLCP regulatory subunit (MYPT1) attenuates the ability of LPS to increase endothelial (EC) permeability. Down-regulation of MYPT1 exacerbates LPS-induced expression of ICAM1 suggesting an anti-inflammatory role of MLCP. To determine whether MLCP contributes to LPS-induced ALI in vivo, we utilized a nanoparticle DNA delivery method to specifically target lung EC. Expression of a C/A MYPT1 reduced LPS-induced lung inflammation and vascular permeability. Further, increased expression of the …

Effects Of High Voltage Nanosecond Electric Pulses On Eukaryotic Cells (In Vitro): A Systematic Review, Tina Batista Napotink, Matej Reberšek, P. Thomas Vernier, Babara Mali, Damijan Miklavčič

Bioelectrics Publications

For this systematic review, 203 published reports on effects of electroporation using nanosecond high-voltage electric pulses (nsEP) on eukaryotic cells (human, animal, plant) in vitro were analyzed. A field synopsis summarizes current published data in the field with respect to publication year, cell types, exposure configuration, and pulse duration. Published data were analyzed for effects observed in eight main target areas (plasma membrane, intracellular, apoptosis, calcium level and distribution, survival, nucleus, mitochondria, stress) and an additional 107 detailed outcomes. We statistically analyzed effects of nsEP with respect to three pulse duration groups: A: 1–10 ns, B: 11–100 ns and C: …

Nanosecond Pulsed Platelet-Rich Plasma (Nsprp) Improves Mechanical And Electrial Cardiac Function Following Myocardial Reperfusion Injury, Barbara Y. Hargrave, Frency Varghese, Nektarios Barabutis, John Catravas, Christian Zemlin

School of Medical Diagnostics & Translational Sciences Publications

Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial …

Relating Ion Release And Ph To In Vitro Cell Viability For Gallium-Inclusive Bioactive Glasses, Timothy J. Keenan, L. M. Placek, T. L. Mcginnity, Mark R. Towler, M. M. Hall, A. W. Wren

Chemical and Biochemical Engineering Faculty Research & Creative Works

A bioactive glass (BG) in which Ga was substituted for Zn was formulated to investigate whether the ionic form of Ga can elicit effects similar to gallium nitrate. The ion release and pH of BG extracts were evaluated, as well as the in vitro cytocompatibility of extracts in contact with mouse fibroblasts and human osteoblasts. After incubation times of 1 year, the glass (TGa-1) containing the smaller Ga-addition (8 mol%) released the most sodium (Na) (1420 mg/L), silicon (Si) (221 mg/L), and Ga (1295 mg/L), while the glass (TGa-2) containing the larger Ga-addition (16 mol%), exhibited release levels between TGa-1, …

Oxygen Mass Transport In Stented Coronary Arteries, Eoin Murphy, Adrian S. Dunne, David Martin, Fergal Boyle

Articles

Oxygen deficiency, known as hypoxia, in arterial walls has been linked to increased intimal hyperplasia, which is the main adverse biological process causing in-stent restenosis. Stent implantation has significant effects on the oxygen transport into the arterial wall. Elucidating these effects is critical to optimizing future stent designs. In this study the most advanced oxygen transport model developed to date was assessed in two test cases and used to compare three coronary stent designs. Additionally, the predicted results from four simplified blood oxygen transport models are compared in the two test cases. The advanced model showed good agreement with experimental …

Self-Powered Microfluidic Device For Rapid Assay Of Antiplatelet Drugs, Bincy Jose, Peter Mccluskey, Niamh Gilmartin, Martin Somers, Dermot Kenny, Antonio J. Ricco, Nigel Kent, Lourdes Basabe-Desmonts

Articles

We report the development of a microfluidic device for the rapid assay in whole blood of platelet-protein interactions indicative of the efficacy of antiplatelet drugs—e.g., aspirin and Plavix, two of the world’s most widely used drugs—in cardiovascular patients. Because platelet adhesion to surface-confined protein matrices is modulated by fluid shear rates at the blood/protein interface, and because such binding is a better indicator of platelet function than platelet self-aggregation, we designed, fabricated, and characterized the performance of a family of disposable, self-powered microfluidic chips with well-defined flow and interfacial shear rates suitable for small blood volumes (≤ 200 µL). We …

Assessment Of Optimized Electrode Configuration In Electrical Impedance Myography Study Using Genetic Algorithm Via Finite Element Model, Somen Baidya

College of Graduate Studies: Theses & Dissertations

Electrical Impedance Myography (EIM) is a neurophysiologic technique in which high- frequency, low-intensity electrical current is applied via surface electrodes over a muscle or muscle group of interest and the resulting electrical parameters (resistance, reactance and phase) are analyzed to isolate diseased muscles from healthy ones. Beside muscle properties, some other anatomic and non-anatomic factors like muscle shape, subcutaneous fat (SF) thickness, inter-electrode distance, etc. also impact the major EIM parameters and thus affect the EIM analysis outcomes. The purpose of this study is to explore the effects of variation in some of these factors impose on EIM parameters and …

An Algorithm For Extracting The Ppg Baseline Drift In Real-Time, Tuan Ngoc Nguyen

Theses: Doctorates and Masters

Photoplethysmography is an optical technique for measuring the perfusion of blood in skin and tissue arterial vessels. Due to its simplicity, accessibility and abundance of information on an individual’s cardiovascular system, it has been a pervasive topic of research within recent years. With these benefits however there are many challenges concerning the processing and conditioning of the signal in order to allow information to be extracted. One such challenge is removing the baseline drift of the signal, which is caused by respiratory rate, muscle tremor and physiological changes within the body as a response to various stimuli.

Over the years …

Predicting Asthma Exacerbations Employing Remotely Monitored Adherence, Isabelle Killane, Imran Sulaiman, Elaine Mac Hale, Aoife Breathnach, Terrence Taylor, Martin Holmes, Richard B Reilly, Richard W Costello

Articles

This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant's inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate …

Oxygen Transport, Shear Stress, And Metabolism In Perfused Hepatocyte-Seeded Scaffolds With Radial Pore Architecture: Experimental And Computational Analyses, Chijioke Mbanu

Wayne State University Dissertations

Several modalities have been proposed as treatments or temporary stop-gap for patients suffering from liver failure until a suitable organ is available. However there is still an urgent need for an off-the-shelf device that can accommodate clinically relevant cell numbers, be cultured at physiological oxygen tensions and, can be fully integrated into and heal the injured hepatic space. In this study we investigated the effects that convective and direct oxygenation had on hepatocyte functionality, morphology and viability while cultured in bulk 3D chitosan scaffolds and perfusion bioreactor systems. Cylindrical chitosan scaffolds with radial directed pore structures were fabricated by a …

A Scalable Low-Cost Cgmp Process For Clinical Grade Production Of The Hiv Inhibitor 5p12-Rantes In Pichia Pastoris, Fabrice Cerini, Hubert Gaertner, Knut Madden, Ilya Tolstorukov, Scott Brown, Bram Laukens, Nico Callewaert, Jay C. Harner, Anna M. Oommen, John T. Harms, Anthony R. Sump, Robert C. Sealock, Dustin J. Peterson, Scott K. Johnson, Stephan B. Abramson, Michael M. Meagher, Robin Offord, Oliver Hartley

Department of Chemical and Biomolecular Engineering: Faculty Publications

In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV …

Retargeting The Clostridium Botulinum C2 Toxin To The Neuronal Cytosol, Benjamin J. Pavlik, Elizabeth J. Hruska, Kevin E. Van Cott, Paul H. Blum

Department of Chemical and Biomolecular Engineering: Faculty Publications

Many biological toxins are known to attack specific cell types, delivering their enzymatic payloads to the cytosol. This process can be manipulated by molecular engineering of chimeric toxins. Using toxins with naturally unlinked components as a starting point is advantageous because it allows for the development of payloads separately from the binding/translocation components. Here the Clostridium botulinum C2 binding/translocation domain was retargeted to neural cell populations by deleting its non-specific binding domain and replacing it with a C. botulinum neurotoxin binding domain. This fusion protein was used to deliver fluorescently labeled payloads to Neuro-2a cells. Intracellular delivery was quantified by …

Finite Element And Probabilistic Analysis Of Soft Tissue Structures Of The Human Lumbar Spine, Dana Joseph Coombs

Electronic Theses and Dissertations

Human lumbar spine mechanics are influenced by soft tissue structures. Understanding and properly modeling these structures can help determine pathology, treatment, and implant design and performance. Finite element models of the L4-L5 level of the lumbar spine are often used, which include a representation of the intervertebral disc and spinal ligaments. Validation of these models are typically based on torque rotation data from a single subject or the models use average properties reported in literature. However, experimental testing reports variation up to 40% in ligament stiffness and even greater variability for annulus fibrosis properties. Probabilistic approaches enable consideration of the …

Anatomy, Implant Selection And Placement Influence Spine Mechanics Associated With Total Disc Replacement, Justin F.M. Hollenbeck

Electronic Theses and Dissertations

Through aging and injury, the intervertebral disc of the lumbar spine can undergo degeneration, leading to collapse of the vertebrae and low back pain, a symptom that affects half the adult population in any given year. In an effort to reduce low back pain, total disc replacement treatment removes the degenerated disc, restores natural height and lordosis of the segment, and preserves motion at the joint. Patient anatomy, implant selection, and implant placement play significant roles in a patient's outcomes after total disc replacement surgery. Thus, the objective of the work presented in this thesis was to develop a suite …

Regional Mechanical Properties And Microstructure Of Ovine Heart Chambers, Shahnaz Javani

Electronic Theses and Dissertations

Mechanical properties of cardiac tissue play an important role in the normal heart function. As a baseline for understanding of physiology and pathophysiology of the heart, and for development and validation of new therapies, it is crucial to first understand the mechanical behavior of the normal heart tissue. Although heart chambers have the same embryonic origin, differences in the development of mechanical properties are expected to manifest over time during the adulthood period. Therefore, the goal of this study was to determine the passive mechanical properties of all heart chambers through a paired comparison study in an ovine model. Ovine …

Multiscale Musculoskeletal Modeling Of The Lower Limb To Perform Personalized Simulations Of Movement, Alessandro Navacchia

Electronic Theses and Dissertations

Computational modeling has been used for many decades to inform design and decision-making in several fields of engineering, such as aerospace, automotive, petroleum, and others. However, it still struggles to have a similar impact in fields of medicine, such as orthopaedics. Three of the challenges that have limited the use of computational modeling in the clinical practice and in product development are model validation, personalization, and realism. Validation is a challenge because several internal parameters of the human body, such as muscle forces, are not safely measurable in vivo and, consequently, a thorough comparison between model outputs …

Expanded 3d Nanofiber Scaffolds: Cell Penetration, Neovascularization, And Host Response, Jiang Jiang, Zhuoran Li, Hongjun Wang, Yue Wang, Mark A. Carlson, Matthew J. Teusink, Matthew R. Macewan, Linxia Gu, Jingwei Xie

Department of Mechanical and Materials Engineering: Faculty Publications

Herein, a robust method to fabricate expanded nanofiber scaffolds with controlled size and thickness using a customized mold during the modified gas-foaming process is reported. The expansion of nanofiber membranes is also simulated using a computational fluid model. Expanded nanofiber scaffolds implanted subcutaneously in rats show cellular infiltration, whereas non-expanded scaffolds only have surface cellular attachment. Compared to unexpanded nanofiber scaffolds, more CD68+ and CD163+ cells are observed within expanded scaffolds at all tested time points post-implantation. More CCR7+ cells appear within expanded scaffolds at week 8 post-implantation. In addition, new blood vessels are present within the expanded scaffolds at …

Noninvasive Measurement Of Electrical Events Associated With A Single Chlorovirus Infection Of A Microalgal Cell, Seung-Woo Lee, Eun-Hee Lee, Gerhard Thiel, James L. Van Etten, Ravi Saraf

Department of Chemical and Biomolecular Engineering: Faculty Publications

Chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) contains a viral-encoded K⁺ channel imbedded in its internal membrane, which triggers host plasma membrane depolarization during virus infection. This early stage of infection was monitored at high resolution by recording the cell membrane depolarization of a single Chlorella cell during infection by a single PBCV-1 particle. The measurement was achieved by depositing the cells onto a network of one-dimensional necklaces of Au nanoparticles, which spanned two electrodes 70 μm apart. The nanoparticle necklace array has been shown to behave as a single-electron device at room temperature. The resulting electrochemical field-effect transistor …

Spatio-Temporal Progression Of Cortical Activity Related To Continuous Overt And Covert Speech Production In A Reading Task, Jonathan S. Brumberg, Dean J. Krusienski, Shreya Chakrabarti, Aysegul Gunduz, Peter Brunner, Anthony L. Ritaccio, Gerwin Schalk

Electrical & Computer Engineering Faculty Publications

How the human brain plans, executes, and monitors continuous and fluent speech has remained largely elusive. For example, previous research has defined the cortical locations most important for different aspects of speech function, but has not yet yielded a definition of the temporal progression of involvement of those locations as speech progresses either overtly or covertly. In this paper, we uncovered the spatio-temporal evolution of neuronal population-level activity related to continuous overt speech, and identified those locations that shared activity characteristics across overt and covert speech. Specifically, we asked subjects to repeat continuous sentences aloud or silently while we recorded …

Gallium-Containing Mesoporous Bioactive Glass With Potent Hemostatic Activity And Antibacterial Efficacy, Sara Pourshahrestani, Ehsan Zeimaran, Nahrizul Adib Kadri, Nicola Gargiulo, Shani Samuel, Sangeetha Vasudevaraj Naveen, Tunku Kamarul, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga⁺³) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …