Biomedical Engineering and Bioengineering Commons^™

Development Of A Lab-On-A-Chip Device For Rapid Nanotoxicity Assessment In Vitro, Pratikkumar Shah

FIU Electronic Theses and Dissertations

Increasing useof nanomaterials in consumer products and biomedical applications creates the possibilities of intentional/unintentional exposure to humans and the environment. Beyond the physiological limit, the nanomaterialexposure to humans can induce toxicity. It is difficult to define toxicity of nanoparticles on humans as it varies by nanomaterialcomposition, size, surface properties and the target organ/cell line. Traditional tests for nanomaterialtoxicity assessment are mostly based on bulk-colorimetric assays. In many studies, nanomaterials have found to interfere with assay-dye to produce false results and usually require several hours or days to collect results. Therefore, there is a clear need for alternative tools that can …

Long-Acting Antituberculous Therapeutic Nanoparticles Target Macrophage Endosomes, Benson J. Edagwa, Dongwei Guo, Pavan Puligujja, Han Chen, Joellyn Mcmillan, Xinming Liu, Howard Gendelman, Prabagaran Narayanasamy

Nebraska Center for Biotechnology: Faculty and Staff Publications

Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl- INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/106 cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/106 cells for native …

Development And Characterization Of An Autologous Whole Cell Breast Cancer Vaccine, Samantha Leigh Kurtz

Graduate Theses and Dissertations

Approximately 40,000 women will die from breast cancer in the United States in 2014. About 90% of these deaths will be due to metastases, rather than the primary tumor and majority of metastases are due to the recurrence and progression of non-metastatic disease. Current adjuvant treatments, such as chemotherapy and radiation, have severe side effects and may result in overtreatment and drug resistance.

Since greater than 90% of patients are diagnosed between stages I-III and have minimal residual disease after treatment, there is an opportunity to treat patients with an autologous breast cancer vaccine. Autologous vaccines under development have a …

Low Molecular Weight Glucosamine/L-Lactide Copolymers As Potential Carriers For The Development Of A Sustained Rifampicin Release System: Mycobacterium Smegmatis As A Tuberculosis Model, Jorge Ragusa

Department of Chemical and Biomolecular Engineering: Theses and Student Research

Tuberculosis, a highly contagious disease, ranks as the second leading cause of death from an infectious disease, and remains a major global health problem. In 2013, 9 million new cases were diagnosed and 1.5 million people died worldwide from tuberculosis. This dissertation aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (molecular core building unit) and L-lactide (GluN-LLA). Stable particles with a very high 50% drug loading capacity were made via electrohydrodynamic atomization. Prolonged …

Characterization Of Bone Material Properties And Microstructure In Osteogenesis Imperfecta/Brittle Bone Disease, John Robert Jameson

Dissertations (1934 -)

Osteogenesis imperfecta (OI) is a genetic disorder primarily associated with mutations to type I collagen and resulting in mild to severe bone fragility. To date, there is very little data quantifying OI cortical bone mechanics. The purpose of this dissertation was to investigate bone microstructure, mineralization, and mechanical properties in adolescents with OI. Characterization studies were performed on small osteotomy specimens obtained from the extremities during routine corrective surgeries. Nanoindentation was used to examine the longitudinal elastic modulus and hardness at the material level for mild OI type I vs. severe OI type III. Both modulus and hardness were significantly …

Virus-Host Mucosal Interactions During Early Siv Rectal Transmission, Wuxun Lu, Fangrui Ma, Alexander Churbanov, Yanmin Wan, Yue Li, Guobin Kang, Zhe Yuan, Dong Wang, Chi Zhang, Jianqing Xu, Mark Lewis, Qingsheng Li

Nebraska Center for Biotechnology: Faculty and Staff Publications

To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggests that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into …

Metabolic Modeling Of Secondary Metabolism In Plant Systems, Lisa M. Leone

Masters Theses

In the first part of this research, we constructed a Genome scale Metabolic Model (GEM) of Taxus cuspidata, a medicinal plant used to produce paclitaxel (Taxol®). The construction of the T. cuspidata GEM was predicated on recent acquisition of a transcriptome of T. cuspidata metabolism under methyl jasmonate (MJ) elicited conditions (when paclitaxel is produced) and unelicited conditions (when paclitaxel is not produced). Construction of the draft model, in which transcriptomic data from elicited and unelicited conditions were included, utilized tools including the ModelSEED developed by Argonne National Laboratory. Although a model was successfully created and gapfilled by ModelSEED …

Using Collagen Binding Poly(N-Isopropylacrylamide) Nanoparticles To Prevent Intravascular Platelet Adhesion And Activation, Anna E. Searle, Alyssa Panitch, James Mcmasters

The Summer Undergraduate Research Fellowship (SURF) Symposium

Balloon angioplasty, the most prevalent non-surgical treatment for Atherosclerosis, damages the endothelial layer of the artery, baring an underlying collagenous layer, which causes platelet adhesion and activation and eventual thrombosis and intimal hyperplasia. Previous work in our lab has used a collagen-binding peptidoglycan, dermatan-sulfate-SILY (DS-SILY), that has been shown to bind to type I collagen and prevent platelet adhesion and activation. Our goal is to fabricate nanoparticle-SILY by cross-linking SILY to a poly(N-isopropylacrylamide) (NIPAm) nanoparticle instead of a DS backbone, while retaining the SILY’s high collagen binding affinity and platelet inhibition capacity observed in DS-SILY. Using a biotin-streptavidin assay, we …

Tissue Engineering: Applications In Developmental Toxicology, Stephanie N. Thiede, Nimisha Bajaj, Kevin Buno, Sherry L. Voytik-Harbin

The Summer Undergraduate Research Fellowship (SURF) Symposium

In vivo toxicology assays are expensive, low-throughput, and often not predictive of a human response. Three-dimensional in vitro human cell-based tissue systems incorporating cell-cell and cell-matrix interactions have promise to provide high-throughput, physiologically-relevant information on the mechanism of the toxin and a more accurate assessment of the toxicity of a chemical before progression to human trials. Quantification of the disruption of vasculogenesis, the de novo formation of blood vessels from endothelial progenitor cells, can serve as an appropriate indicator of developmental toxicity since vasculogenesis is critical to the early development of the circulatory system. The current routinely used in vitro …

Tumor-Microenvironment-On-Chip To Mimic Tumor Heterogeneity, Victoria Noe-Kim, Altug Ozcelikkale, Bumsoo Han

The Summer Undergraduate Research Fellowship (SURF) Symposium

Ductal Carcinoma In Situ (DCIS) is a non-invasive cancer that forms around breast milk ducts that can potentially progress into invasive breast cancer if untreated. Lack of models to study its diverse pathophysiology and differential response to treatments poses a challenge to develop standard treatment modalities with improved therapeutic outcomes. The traditional in vitro models such as cell monolayer are convenient but insufficient to represent the physiological characteristics of DCIS tumor microenvironment and often fail to predict clinical outcomes. The animal models effectively simulate the in vivo environment but also lack the ability to control the environmental parameters to match …

Characterization Of Swelling Ratio And Water Content Of Hydrogels For Cartilage Engineering Applications, Emily E. Gill, Renay S.-C. Su, Julie C. Liu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Due to the high prevalence of arthritis and cartilage-related injuries, tissue engineers are studying ways to grow cartilage tissue replacements. Resilin, an elastomeric protein found in insect cuticles, is known for its extraordinary resilience and elasticity. In previous studies, recombinant resilin-based hydrogels, or cross-linked protein networks, exhibited potential for use in cartilage tissue scaffolds. Our lab successfully developed resilin-based proteins with a sequence based on the mosquito gene and showed that resilin-based hydrogels possess mechanical properties of the same order of magnitude as native articular cartilage. In addition, these mechanical properties can be controlled by changing the protein concentration. To …

Biological Implications Of Satellite Cells For Scaffold-Based Muscle Regenerative Engineering, Maggie R. Del Ponte, Charter Chain, Meng Deng Dr., Feng Yue Dr., Shihuan Kuang Dr.

The Summer Undergraduate Research Fellowship (SURF) Symposium

Satellite cells are anatomically localized along the surface of muscle fibers and have been regarded as a population of muscle-specific progenitors that are responsible for muscle regeneration. In response to muscle injuries, satellite cells are activated to enter the cell cycle, then proliferate and differentiate into mature muscle cells to regenerate damaged myofibers. Unfortunately, this natural repair mechanism is interrupted in conditions such as muscle degenerative diseases or volumetric muscle loss. The function of stem cells is regulated by signals from their local microenvironment which is called the stem cell niche. Current satellite cell-based strategies such as direct cell transplantation …

Spatiotemporal Changes In Nuclear Strain Measured By Traction Force Microscopy, Ryan D. Watts, Corey Neu, Jonathan Henderson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The knowledge of how cells interact with and sense their surroundings is missing the key components of time dependency and how substrate stiffness affects amount and rate of strain. This new knowledge of cell-substrate interaction can be applied further to research regarding chromatin spatiotemporal dynamics to better understand gene accessibility for transcription. Studying how the cell functions on a deeper level will provide understanding of cellular morphological changes and proliferation. This study uses the methods of optical microscopy and traction force microscopy (TFM) to image substrate deformation as well as analyze its strain profile to find where forces are interacting …

Microvascular Topology And Intravascular Endothelial Cell Labeling In The Gracilis Anterior Muscle Of Balb/C Mice, Paul Heckler Ii

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) affects approximately 200 million individuals globally. The major underlying cause of PAOD is an inflammatory disease known as atherosclerosis, which results from the build-up of low-density lipoproteins (LDL) in the sub-intimal space. This initiates a complex cascade of events that lead to plaque growth. Plaque growth can then expand into the lumen of the vessel and result in occlusion and/or thrombosis. Symptoms of the disease can include claudication, ulcers, and/or gangrene, although many patients are asymptomatic. Similar to other forms of ischemic disease, risk factors for PAOD include hypertension, diabetes, and smoking. Common treatments include …

Construction Of 3d Biomimetic Tissue Niches For Directing Pancreatic Lineage Differentiation Of Human Embryonic Stem Cells, Weiwei Wang

Graduate Theses and Dissertations

The potential of human embryonic stem cells (hESCs) to differentiate into insulin producing beta cells offers great hope for cell-based therapy for diabetes treatment. However, in vitro pancreatic differentiation of hESCs remains challenging. In the past decade, most protocols for differentiating pancreatic cells have been focused on the use of signaling molecule cocktails on 2D substrates. Studies on embryonic development biology strongly suggest that extracellular matrix (ECM) plays a critical role on hESCs behavior. In this work, we first established a 3D collagen scaffold culture system for hESCs differentiating into definitive endoderm (DE), which is the first and most important …

A Novel Cell Based Assay For Mmp Inhibitor Screening, Pantrika Krisanarungson

Graduate Theses and Dissertations

Up to date, a plethora of protein based materials are used as implants to stimulate tissue regeneration or fillers to alleviate tissue or organ impairment. This includes glottal insufficiency, urinary bladder incontinence and especially in cosmetic industrial to improve facial contour. Once in vivo, protein-based materials are decomposed by cell secreted matrix metalloproteinases (MMP) and lose their volume within months. By introducing MMP inhibitor (MMPI), the extent of material degradation over time may be reduced. In this dissertation, the development of cell-based assay capable of identifying MMPI candidates for protein-based implant lifetime prolongation is described. To visualize the degradation, DQ-gelatin, …

Application Of Limited Mixing In The Hele-Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

Md Mahmudur Rahman

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

Thermoelectric Elisa For Quantification Of 8ohdg In A Microfluidic Device, Gergana Nestorova

Doctoral Dissertations

This research demonstrates the feasibility of a novel method for performing thermoelectric enzyme-linked immunosorbent assay (ELISA) in a microfluidic device. The feasibility of the thermoelectric ELISA is demonstrated by measuring the concentration of 8-hydroxy 2-deoxyguanosine (8OHdG) in urine samples from amyloid precursor protein (APP) transgenic mice. The detection method is based on formation of a complex between 8OHdG and anti-8OHdG capture antibody conjugated to biotin. The complex is immobilized over the measuring junctions of a thermopile via biotin streptavidin interaction. The concentration of the analyte is determined by using enzyme linked secondary IgG antibody specific to the primary one. The …

Investigation Of Membrane Mechanics Using Spring Networks: Application To Red-Blood-Cell Modelling, Mingzhu Chen, Fergal Boyle

Articles

In recent years a number of red-blood-cell (RBC) models have been proposed using spring networks to represent the RBC membrane. Some results predicted by these models agree well with experimental measurements. How- ever, the suitability of these membrane models has been questioned. The RBC membrane, like a continuum mem- brane, is mechanically isotropic throughout its surface, but the mechanical properties of a spring network vary on the network surface and change with deformation. In this work spring-network mechanics are investigated in large deformation for the first time via an assessment of the effect of network parameters, i.e. network mesh, spring …

Commodification Of The Female Egg: Stem Cell Technology And The Future, Rachel Ostander

North Carolina Central University Science & Intellectual Property Law Review

No abstract provided.

Functional Vasodilation Is Impaired In Arterialized Capillaries In The Spinotrapezius, Joshua P. Cutts

Biomedical Engineering

Ischemic diseases are the result of atherosclerotic plaques, which occlude conduit arteries. Ischemic disease in different tissues leads to different conditions, such as coronary artery disease (CHD), cerebrovascular disease (CVD), and peripheral arterial occlusive disease (PAOD). Patient vasculature architecture is variable; some patients having many collateral vessels, which are connect one arterial branch to another, and readily serve as natural bypass routes to atherosclerotic occlusions, to enlarge and provide blood flow to tissue distal to the occlusion. Patients with many natural collateral vessels are ischemia protected. Unfortunately, not all patients have collateral arterioles to remodel into conduit vessels and provide …

Developing Defined And Scalable 3d Culture Systems For Culturing Human Pluripotent Stem Cells At High Densities, Yuguo Lei, Daeun Jeong, Jifang Xiao, David V. Schaffer

Department of Chemical and Biomolecular Engineering: Faculty Publications

Human pluripotent stem cells (hPSCs)—including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)—are very promising candidates for cell therapies, tissue engineering, high throughput pharmacology screens, and toxicity testing. These applications require large numbers of high quality cells; however, scalable production of human pluripotent stem cells and their derivatives at a high density and under well-defined conditions has been a challenge. We recently reported a simple, efficient, fully defined, scalable, and good manufacturing practice (GMP) compatible 3D culture system based on a thermoreversible hydrogel for hPSC expansion and differentiation. Here, we describe additional design rationale and characterization of this …

Development And Implementation Of Assessment Methods For Tissue-Engineered Blood Vessel Mimics, Tanner Stevenson

Biomedical Engineering

Coronary Artery Disease (CAD), the most prevalent form of heart disease, is the result of clogged or damaged coronary arteries and claims around 380,000 Americans annually. A common treatment for CAD involves placing a stent into the artery in order to open the lumen and support the native tissue—a procedure that drastically reduces patient recovery times in comparison to heart bypass surgery. However, stents do not always interact well with the body and require additions such as surface coatings or drug elution in order for additional biocompatibility. These additions necessitate extensive in vitro and in vivo testing which are expensive …

Fluid Flow-Induced Mesenchymal Stem Cell Migration: Role Of Fak And Rock Mechanosensors, Brandon D. Riehl

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

The study of mesenchymal stem cell (MSC) migration under mechanical stimulation conditions with investigation of the underlying molecular mechanism could lead to a better understanding and outcomes in stem cell-based regenerative medicine. MSCs having multipotent regenerative capability exist in niches in the bone marrow, muscle, vasculature, and in other tissues throughout the body, and their migration through tissues and vasculature for the repair of damaged tissue is a key process of cell and tissue homeostasis, remodeling, and regeneration. While cell migration in response to cytokines and other chemo-attractants is relatively well understood, little is revealed in regard to the effect …

Application Of Limited Mixing In The Hele-Shaw Geometry In Fabrication Of Janus Hydrogels, Md Mahmudur Rahman

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

It is widely accepted that cells behave differently responding to the stiffness of their extracellular matrix (ECM). Such observations were made by culturing cells on hydrogel substrates of tunable stiffness. However, it was recently proposed that cells may sense how strongly they are tethered to ECM, not the local stiffness of ECM. To investigate both hypotheses, we developed a method to fabricate Janus polyacrylamide (PAAM) gels. We squeeze two drops of different concentrations in the Hele-Shaw geometry to generate radial Stokes flow. When the drops coalesce, limited mixing occurs at the interface due to the narrow confinement, and diffusion normal …

Humidity Effect On The Structure Of Electrospun Core-Shell Pcl-Peg Fibers For Tissue Regeneration Applications, Adam P. Golin

Electronic Thesis and Dissertation Repository

With the aim of creating a biodegradable scaffold for tympanic membrane (TM) tissue regeneration, core-shell nanofibers composed of a poly(caprolactone) shell and a poly(ethylene glycol) core were created using a coaxial electrospinning technique. In order to create fibers with an optimal core-shell morphology, the effect of relative humidity (RH) on the core-shell nanofibers was systematically studied, with a FITC-BSA complex encapsulated in the core to act as a model protein. The core-shell nanofibers were electrospun at relative humidity values of 20, 25, 30, and 40% RH within a glove box outfitted for humidity control. The core-shell morphology of the fibers …

Utilizing Fast Spin Echo Mri To Reduce Image Artifacts And Improve Implant/Tissue Interface Detection In Refractory Parkinson’S Patients With Deep Brain Stimulators, Subhendra N. Sarkar, Pooja R. Sarkar, Efstathios Papavassiliou, Rafael Rojas

Publications and Research

Introduction. In medically refractory Parkinson’s disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detectDBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity.

Methods. Using an IRB approved protocol 8 advanced PDpatientswere imagedwithinMRconditional safety guidelines at lowRF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences.The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads.

Results …

Bioengineered Hearts, Rivky Loeb

The Science Journal of the Lander College of Arts and Sciences

Heart disease is one of the highest causes for fatality in the world. Although many such diseases can be treated by a heart transplant, this in itself can cause countless problems. Aside from the high demand for donor hearts, there is the risk of the patient’s immune system rejecting the transplanted heart. A bioengineered heart would reduce the need for donor hearts, and thus save countless lives. Finding a suitable scaffold, obtaining appropriate cells, and ensuring that the tissue will function properly are the main focuses in creating an artificial heart. While most of the studies done have been concentrated …

Tissue Engineering Scaffold Fabrication And Processing Techniques To Improve Cellular Infiltration, Casey Grey

Theses and Dissertations

Electrospinning is a technique used to generate scaffolds composed of nano- to micron-sized fibers for use in tissue engineering. This technology possesses several key weaknesses that prevent it from adoption into the clinical treatment regime. One major weakness is the lack of porosity exhibited in most electrospun scaffolds, preventing cellular infiltration and thus hosts tissue integration. Another weakness seen in the field is the inability to physically cut electrospun scaffolds in the frontal plane for subsequent microscopic analysis (current electrospun scaffold analysis is limited to sectioning in the cross-sectional plane). Given this it becomes extremely difficult to associate spatial scaffold …

Analysis And Modeling Of The Roles Of Actin-Myosin Interactions In Bladder Smooth Muscle Biomechanics, Seyed Omid Komariza

Theses and Dissertations

Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length …