Search Results (1 - 25 of 687 Results)

Sort By  
Sort Dir
 
Results per page  

Bodle, Sarah J.Adhesion Based Early Detection of Colorectal Cancer
Master of Science (MS), Ohio University, 2017, Biomedical Engineering (Engineering and Technology)
Colorectal cancer (CRC) is the fourth most diagnosed cancer and the second leading cause of cancer death with 135,430 new cases and 50,260 deaths predicted to occur in the United States in 2017 “Cancer Statistics Center,” ACS Available: http://cancerstatisticscenter.cancer.org/. With current screening tests, the percentage of diagnosis occurring at localized, regional, distant, and unknown stages are 39, 35, 21, and 5 percent with corresponding 5-year survival rates of 90.1, 71.2, 13.5, and 35.5 percent, respectively “Cancer of the Colon and Rectum - Cancer Stat Facts,” NCI Available: https://seer.cancer.gov/statfacts/html/colorect.html. The high mortality rate can be attributed to the percentage of later stage diagnosis. As such, there is a demand for novel diagnostics that increase the percentage of diagnosis occurring at an early stage when the survival rate is most promising. It is possible that a novel diagnostic could be designed based on the increased expression of adhesion molecules on transforming tissue relative to normal tissue. Transforming tissue would be identified by detection constructs consisting of microparticles conjugated to ligands cognate to the adhesion molecules. The detection constructs would be administered to the epithelium of the colorectum via a spray catheter through the biopsy channel of an endoscope during colonoscopy. The broad working hypothesis of this study is that differential expression of adhesion molecules on transforming and cancerous, relative to normal tissue, can be exploited to develop a ligand conjugated particle based in situ diagnostic assay. As a first step, the goal of this thesis was to characterize the expression of sialyl Lewis A (sLeA), sialyl Lewis X (sLeX), and CD44 on transforming and cancerous, relative to normal, cell lines and tissues. Expression levels of CD44 proteins as well as sLeA and sLeX glycans on cancerous relative to normal human colorectal cell lines were quantified by flow cytometry. This analysis revealed that CD44v3 and CD44v5 proteins have increased expression on cancerous relative to normal human colorectal cell lines when identified by anti- CD44v3 mAb 3G5 and anti- CD44v5 mAb VFF-8. In addition, sLeA and sLeX glycans have increased expression on cancerous relative to normal human colorectal cell lines when identified by anti- sLeA mAb KM231, anti- sLeA mAb C241:5:1:4, anti- sLeX mAb CSLEX1, anti- sLeX mAb FH6, and anti- cutaneous lymphocyte antigen (CLA) mAb HECA-452. Expression levels of sLeA and sLeX were characterized on human colorectal tissues by immunohistochemistry. The average percent staining of each core for sLeA is significantly lower on normal tissues and normal adjacent tissues compared to stage I adenocarcinoma tissues when identified by anti- sLeA mAb KM231 and anti- sLeA mAb C241:5:1:4. Results also show the average percent of staining of each tissue core for sLeX is significantly lower on normal tissues and normal adjacent tissues compared to stage I adenocarcinoma tissues when identified by anti- sLeX mAb CSLEX1. Anti- CLA mAb HECA-452 recognizes a carbohydrate domain shared by glycans including sLeA and sLeX. Results show the average percent of each core staining positive for glycans identified by anti- CLA mAb HECA-452 is significantly lower on normal tissues and normal adjacent tissues compared to stage I adenocarcinoma tissues. Interestingly, the results indicate that the average percent of glands staining positive for sLeA is significantly higher on normal tissues compared to neoplasia tissues when identified by anti- sLeA mAb C241:5:1:4. In summary, this thesis revealed differences between the expression of CD44, sLeA, and sLeX on transforming and cancerous versus normal cell lines and tissues. These differences in adhesion molecule expression could be exploited for the design of a novel assay for the diagnosis of colorectal cancer.

Committee:

Douglas Goetz (Advisor); Monica Burdick (Committee Member); David Drozek (Committee Member); Ramiro Malgor (Committee Member); Amir Farnoud (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

colorectal; cancer; diagnostic; CD44; sialyl Lewis A; sialyl Lewis X

Camardo, Andrew TC-JUN N-TERMINAL KINASE INHIBITORY NANOTHERAPEUTICS FOR REGENERATIVE ELASTIC MATRIX REPAIR IN ABDOMINAL AORTIC ANEURYSMS
Master of Science in Biomedical Engineering, Cleveland State University, 2017, Washkewicz College of Engineering
Abdominal aortic aneurysms (AAA) are localized expansions of the aorta wall that continue to grow until they reach a critical size and fatally rupture. This growth is driven by the chronic disruption, degradation, and subsequent loss of aortal wall elastic fibers by matrix metalloproteinases (MMPs) secreted by inflammatory cells recruited to the aorta wall following an injury stimulus, and the inherent inability of vascular smooth muscle cells (SMCs) to naturally repair or regenerate elastic fibers. This leads to a net loss of elastic matrix and the continuing weakening of the aortal wall until eventual rupture. Current treatments seek to reinforce the vessel wall with grafts or stents, but do not arrest or reverse AAA growth. Therefore, inhibiting the proteolytic degradation of the elastic matrix while also stimulating elastic matrix neoassembly is needed to stop AAA growth and regenerate the vessel wall. We have previously shown utility of doxycycline (DOX), an MMP inhibitor drug, to stimulate elastic matrix neoassembly and crosslinking at low µg/ml doses in addition to inhibiting MMPs. We currently show in aneurysmal SMC cultures, that effects of exogenous DOX in this dose range are linked to its upregulation of transforming growth factor beta (TGF-ß1) via its inhibition of the regulatory protein c-Jun-N-terminal kinase isoform 2 (JNK 2). We have identified a DOX dose range that stimulates elastogenesis and crosslinking without adversely impacting cell viability. Using JNK 2 inhibition as a metric for pro-regenerative matrix effects of DOX, we further demonstrate that sustained, steady state release of DOX at the useful dose, from poly(ethylene glycol)-poly(lactic glycolic acid) nanoparticles (NPs) provides pro-elastogenic and anti-proteolytic effects that could potentially be more pronounced than that of exogenous DOX. We attribute these outcomes to previously determined synergistic effects provided by cationic amphiphile groups functionalizing the polymer NP surface. Released DOX inhibited expression and phosphorylation of JNK to likely increase expression of TGF-ß1, which is known to increase elastogenesis and lysyl oxidase-mediated crosslinking of elastic matrix. Our results suggest that JNK inhibition is a useful metric to assess pro-elastic matrix regenerative effects and point to the combinatorial regenerative benefits provided by DOX and cationic-functionalized NPs.

Committee:

Anand Ramamurthi, Ph.D. (Committee Chair); Chandrasekhar Kothapalli, Ph.D. (Committee Member); Nolan Holland, Ph.D. (Committee Member)

Subjects:

Biomedical Engineering

Varghai, KavehThe Production of Hydroxyapatite Standards, Used for Post CBCT Scan Hounsfield Unit Calibration
Master of Sciences, Case Western Reserve University, Biomedical Engineering
We think that we can help ease patients’ concerns by altering diagnostic x-rays. Our goal is to use CT information to pre-surgically determine the likelihood of success of an operation. This technique could help expectation setting or, moreover, could help oral physicians make procedural decisions which result in higher rates of implant stability and functionality. Currently, cone beam computerized tomographies (CBCT) are commonly used in the dental community for morphological assessment of the mandible and maxilla. Previous studies have shown the potential of using a single set of phantoms in the oral cavity, to derive Hounsfield Units (HU). However, due to the polychromatic x-ray source in CBCT scanners, variation in average grey level for a single phantom exists, as a function of location. This thesis will focus on using common biomaterials, used in biomedical implants, to design and fabricate a set of standards, small enough so that a single set is fixed adjacent to the region of interest (ROI). This set of phantoms would allow dental clinicians to quantitatively assess bone quality by ultimately comparing derived HU to mass density without the need for expensive medical software.

Committee:

Steven Eppell, Ph.D (Advisor); Russell Wang, DDS, MSD (Committee Member); David Wilson, Ph.D (Committee Member)

Subjects:

Biomedical Engineering

Seshadri, Dhruv RamakrishnaImmuno-nanotherapeutics to Inhibit Macrophage Polarization for Non-Small-Cell Lung Cancers
Master of Sciences, Case Western Reserve University, 2017, Biomedical Engineering
Lung cancer is the leading cause of cancer-related mortalities in the USA with a five-year survival rate of ~15%. For patients with Non-Small-Cell Lung Cancer (NSCLC), chemotherapy, oncogene targeted therapy, or immunotherapy are the primary modes of treatment. Response rates to immunotherapies for NSCLCs are < 20%, due to the tumor micro-environment (TME) that favors immune-evasion and pro-tumorigenic pathways such as macrophage polarization from a pro-inflammatory (M1) to a pro-tumorigenic/angiogenic (M2) phenotype. Additionally, the TME is compromised by the chronic enzymatic breakdown of the elastic matrix which catalyzes polarization. Exogenous delivery of Doxycycline (DOX) has shown to inhibit the M1-M2 phenotypic switch. We explored the utility of antibody-conjugated DOX-poly(ethylene glycol)-poly(lactic glycolic-acid) (PEG-PLGA) nanoparticles (NPs) to inhibit macrophage polarization and demonstrate that steady-state release of DOX from these NPs is possible in a low dose range to inhibit polarization and repolarize macrophages back to the M1 phenotype.

Committee:

Anand Ramamurthi (Advisor); Eben Alsberg (Committee Member); Colin Drummond (Committee Member)

Subjects:

Biomedical Engineering; Biomedical Research; Polymer Chemistry; Polymers

Keywords:

Tumor Microenvironment, Nanomedicine, Nanoparticles, Polymers, Lung Cancer, Macrophages, Immunotherapy, Extracellular Matrix, Elastin

Gabbard, Ryan DwightIdentifying the Impact of Noise on Anomaly Detection through Functional Near-Infrared Spectroscopy (fNIRS) and Eye-tracking
Master of Science in Biomedical Engineering (MSBME), Wright State University, 2017, Biomedical Engineering
Occupational noise frequently occurs in the work environment in military intelligence, surveillance, and reconnaissance (ISR) operations. This impacts cognitive performance by acting as a stressor, potentially interfering with the analysts’ decision making process. In this study the effects of different noise stimuli on analysts’ performance and workload in anomaly detection were investigated by simulating a noisy work environment. Functional near infrared spectroscopy (fNIRS) was utilized to quantify oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbD) concentration changes in the prefrontal cortex (PFC), as well as behavioral measures which include eye-tracking, reaction time, and accuracy rate. It was found that HbO for some of the channels analyzed were significantly different across noise types (p<0.05). The results indicated that HbO activation for short intermittent noise stimuli was greater in the PFC compared to long intermittent noises. Target transition rates were also significantly higher (p<0.05) for no noise conditions compared to noise filled environments. These approaches using fNIRS in conjunction with an understanding of the impact on human analysts in anomaly detection, could potentially lead to better performance by optimizing work environments.

Committee:

Mary Fendley, Ph.D. (Advisor); Nasser Kashou, Ph.D. (Committee Member); Rik Warren, Ph.D. (Committee Member)

Subjects:

Biomedical Engineering; Neurosciences

Keywords:

functional near-infrared spectroscopy; workload; prefrontal cortex; eye tracking; noise; anomaly detection

Liu, YuchiDEVELOPMENT OF DYNAMIC PHOSPHORUS-31 AND OXYGEN-17 MAGNETIC RESONANCE SPECTROSCOPY AND IMAGING TECNIQUES FOR PRECLINICAL ASSESSMENT OF ENERGY METABOLISM IN VIVO
Doctor of Philosophy, Case Western Reserve University, 2018, Biomedical Engineering
Adenosine triphosphate (ATP) is the energy currency that maintains physiological activities of the cell. The major source of ATP in aerobic organisms is oxidative phosphorylation occurred in mitochondria. Disruptions of oxidative phosphorylation are associated with various metabolic diseases. Hetero-nuclei MRI plays an important role in assessing functional cell processes such as oxidative metabolism. Specifically, phosphorous-31 (31P) and oxygen-17 (17O) MRS/MRI provide a non-invasive tool to probe mitochondrial oxidative capacity and oxygen consumption, respectively. However, hetero-nuclei MRI in general is challenging due to the low in vivo concentrations and low MR sensitivity. Long acquisition time is usually required even with low spatial resolution. In this thesis, novel approaches for imaging 31P and 17O with high spatial resolution and temporal resolution were developed and demonstrated in small animals at high fields. In particular, this thesis focused on fast 31P MR Spectroscopic Imaging (MRSI) and 17O MRI approaches with non-Cartesian encoding schemes that assess mitochondrial function in skeletal muscle and cerebral oxygen metabolism/water movement across the blood-brain barrier (BBB), respectively. 15 Four projects are described in this thesis. First, an ischemia-reperfusion protocol was established to evaluate mitochondrial oxidative capacity in type 2 diabetic rats using 31P MRS. Second, a fast dynamic 31P MRSI method using a low-rank model was developed and demonstrated in rat skeletal muscle during ischemia-reperfusion. Third, a dynamic 17O MRI method using golden-angle radial acquisition combined with k-space weighted image contrast (KWIC) reconstruction was developed and validated in simulation studies and phantom experiments. Finally, the 17O MRI method was demonstrated in a mouse model with glioblastoma (GBM) to assess the water movement across BBB after a bolus in injection of 17O-labeled water. The 17O MRI approach was also applied to a mouse model of middle cerebral artery occlusion (MCAO) in 17O-labeled gas inhalation experiments to assess cerebral oxygen metabolism in vivo. The success of these studies will pave the way for fast metabolic imaging using 31P and 17O MRI techniques and allow for the assessment of metabolic alterations in various disease models, such as diabetes, ischemic stroke, etc.

Committee:

Xin Yu, Sc.D. (Advisor); Nicole Seiberlich, Ph.D. (Committee Chair); Mark Griswold, Ph.D. (Committee Member); John Kirwan, Ph.D. (Committee Member); Nicola Lai, Ph.D. (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

magnetic resonance imaging, magnetic resonance spectroscopy, energy metabolism, phosphorus-31, oxygen-17

Yuning, GuFast Magnetic Resonance Fingerprinting of Mouse Using a Spiral Trajectory
Master of Sciences, Case Western Reserve University, Biomedical Engineering
Purpose: To fulfill preliminary implementation of spiral-based magnetic resonance fingerprinting (MRF) sequences for fast T1 and T2 mapping of mouse brain at 7T. Methods: MRF-bSSFP and MRF-FISP sequence sensitive to T1 and T2 were implemented with a variable density spiral trajectory, which fully sample the k-space with 48 interleaves. Phantom and mouse brain studies were performed on a 7T animal scanner. Undersample capability was explored by retrospective undersampling, and validated by directly undersampled data on scanner. Results: With inner 10×10 k-space fully sampled by 6 interleaves, an 8-fold acceleration was validated in vitro and in vivo for both MRF sequences, corresponding to a 2.5-minute scan under current implementation.

Committee:

Xin Yu (Advisor); Chris Flask (Committee Member); Weihong Guo (Committee Member)

Subjects:

Biomedical Engineering

Jia, XinghuaPhysical Origin of Biological Propulsion and Inspiration for Underwater Robotic Applications
Doctor of Philosophy, The Ohio State University, 2017, Biomedical Engineering
Robotic design, especially in underwater robots, is critical to research, national defense, deep sea exploration and sea disaster rescue. Developing an advanced underwater robot, however, is complicated, as it involves propulsion, depth regulation, motion between propellers and other auxiliary system coordination, as well as sensing and feedback signals synchronization. Additionally, it is more challenging to manage the aquatic environment and guarantee the robotic design. In particular, the propulsion system could fit well in this environment and allow for efficient swimming. These challenges make the development of an underwater robot much more difficult, and finding the best solutions to building a robot in a standard and robust manner is critical to satisfying the large amount of requirements of the underwater robots in different perspectives. Aquatic creatures have developed swimming capabilities far superior in many ways to what has been achieved by nautical science and technology and have inspired alternative ideas of developing smart and advanced novel robotic mechanisms for propulsion in different fluid environments. Many bioinspired aquatic robots mimic the structure design, locomotion behaviors and even control method of their counterparts in nature and achieved great swimming performance. The further development of a more general design methodology for bioinspired underwater robots, however, has been impeded due to the diversity of biological sources for underwater propulsion. Consequently, there have been several studies attempting to understand basic propulsion principles to synchronize the biological diversity. In this dissertation, we first review the current stages and challenges of design of underwater robots. Afterwards, we provided a methodology for the design of efficient underwater robots from a biological perspective at multiple scales. To achieve this goal, we introduced the unique propulsion features of aquatic species in terms of locomotion mechanism as the swimmer increased in size from the micro/nanoscale to the macro-scale. Then, we discussed the biological propulsion principles for aquatic robotic design, including design of propeller, body, propulsion appendages, locomotion control and auxiliary system. In addition, we introduced the method for the implementation of bioinspired robots, including mechanical design, electronic engineering and system integration (Chapter 1). The following chapters show that four aquatic robots from the micro/nanoscale to the macro-scale were designed by learning unique features from biology and providing specific investigation of propulsion principle for robotic design at each scale. We validated and demonstrated the design of each robot using both mathematical model based simulation and hardware implemented robot experiments. In chapter 2, propulsion was investigated at micro/nanoscale (body length<10-2m). Due to the constraints imposed at micro/nanoscale which has low Reynolds number (Re < 0.1), the design of efficient propulsive systems for nanorobots has proven challenging. An approach for the design of an efficient nanorobotic propulsive system was proposed. First, resistive force theory was used to develop a dynamic model for the propulsion of nanorobots, accounting for the fluid dynamics generated by the propeller (flagellum). Second, an optimal control problem was formulated to balance the trade-off between energy utilization and tracking efficiency. Finally, simulations were conducted to analyze the effect of different body to flagellum ratios (BFR) on propulsive efficiency. It was found that the optimal flexural rigidity of the nanorobot propeller was 5.8×10-19 N·m2, within the range of sperm flagellum, 0.7×10-19 -74.0×10-19 N·m2. Further, simulations of multiples BFRs demonstrated that multipoint actuation of the nanopropeller was more efficient at BFRs of less than 1.0, while single actuation was only effective for nanorobots with a BFR >0.2. The results from this study provide useful insight for the design of nanorobotic propulsive systems, in terms of energy efficiency and trajectory tracking accuracy. In chapter 3, propulsion was investigated at transition scale by using example of whirligig beetle inspired robot. The whirligig beetle, claimed to be one of the most energy-efficient swimmers in the animal kingdom, has evolved a series of propulsion strategies that may serve as a source of inspiration for the design of propulsion mechanisms for energy-efficient surface swimming. In this study, we introduce a robot platform that was developed to test an energy-efficient propulsion mechanism inspired by the whirligig beetle. A propeller-body-fluid interaction dynamics model is proposed and based on this model, the propeller flexural rigidity and beating patterns are optimized in order to achieve energy-efficient linear swimming and turning. The optimization results indicate that a propeller with decreasing flexural rigidity enhances vortex shedding and improves thrust generation. It has also been found that an alternating asymmetrical beating sequence and optimal beating frequency of 0.71 Hz improves propulsion efficiency for linear swimming of the robot. The alternating beating of the outboard propellers and the unfolded inboard propellers working as brakes results in efficient turning with a smaller turning radius. Both simulation and experimental studies were conducted and the results illustrate that decreasing flexural rigidity along the propeller length, an oscillating body motion, and an S-shaped trajectory are critical for energy-efficient propulsion of the robot. In chapter 4, a generic propulsion method, undulatory locomotion was investigated by comparing the propulsion principles across scale, expecting to come out a guidance for the robot design at multiple scales. In nature, swimmers commonly utilize undulation for propulsion. The Undulatory locomotion patterns, in fluid environments, at different Reynolds (Re) numbers (i.e., scale) vary as a result in variation among aspects that affect undulation patterns. Aspects include actuation. Swimmer’s inertia, damping, stiffness, and fluid viscosity. Here, we investigated the natural propulsion principles driving anguilliform and carangiform undulation using spermatozoa, eels, alligators, and trout fish as a means to identify universal aquatic propulsion principles and enhance underwater robotic design. Through biological observations of these species, we identified that as propulsion area stiffness increased, wave number decreases and mass center shifts away from the propulsion area, indicating a conserved biological trend for undulation based swimming that could be applied to designing bio-inspired swimming robotics. To quantitatively test and investigate the mechanistic aspects of this biological trend, a hydrodynamics model, combining resistive force and reactive force theory across scales, was formulated. Using this model, simulations were used to determine the material and kinematic features for effective propulsion. We found that for material features, simulation results showed mass had a diminishing effect as Re increased, while elasticity demonstrated the opposite trend. For the kinematics parameters, simulation results showed that a larger Re usually corresponded to a smaller optimal wavenumber, an increased amplitude, but the amplitude has larger frequency dependent behavior. These results were experimentally validated using a modular robotic platform built to allow robot disassemble and reassemble as a means to mimic undulation modes of the four biological swimmers and controlled by a Central Pattern Generators (CPGs) based algorithm and a PD control. Experimental results validated our simulation and biological findings; as well as, demonstrated a conserved aquatic propulsion principle for underwater swimming that could be translated to the design of future autonomous underwater vehicles with optimal propulsion mechanisms. In chapter 5, an autonomous underwater vehicle was designed by integrating several propulsion mechanism to allow efficient swimming. Underwater propulsion using flexible propeller is usually observed in aquatic species. Unique propulsion features, such as three dimensional (3D) propulsion surface and the manipulation of the fluid through the coordination of multiple propellers allow energy-efficient swimming with high maneuverability. In this study, propulsion features from four aquatic animals, including batoidea fish, diving beetle, alligator and box fish, were used to inspire an autonomous under vehicle (AUV). A 1.3 meter long robot was built to implement the AUV locomotion. Modular design method was employed. Five propulsion modules and one central control module with independent power, communication and control system were integrated to the AUV body. This design significantly increased the operation robustness of the AUV. Five propellers that actuated by 15 motors were designed to allow three propulsion pattern, including flapping, rowing and undulating motion, provided big potentials for agile swimming. A 3D hydrodynamics model that incorporate resistive and reactive force theory was constructed for the quantitatively characterize the AUV’s underwater swimming. A hybrid control method that combines the adaptive control, Central pattern generators based control and PD control were developed to achieve optimal synchronization of the multiple propellers. Finally, simulation and experiments were conducted, and the results show the effectiveness of the proposed AUV design. This insights dawn from this paper provided a guidance for the next generation of AUV using flexible propellers To conclude, we proposed and demonstrated a design methodology for aquatic robotics from biological perspective. We identified and extracted biological principles for efficient propulsion and derived the robotic design after theoretical optimization. Experiment results from four types of robotic platform demonstrated the effectiveness of the proposed aquatic robotic design at multiple scales.

Committee:

Mingjun Zhang (Advisor); Yi Zhao (Committee Member); Xiaoming He (Committee Member); Derek Hansford (Committee Member)

Subjects:

Biomedical Engineering

Fox, Jonathan MCathepsin K Targeting Matrix Regenerative Nanoparticles for Small Abdominal Aortic Aneurysm Repair
Master of Science in Biomedical Engineering, Cleveland State University, 2017, Washkewicz College of Engineering
Abdominal aortic aneurysms (AAAs) are characterized by the loss of elasticity in the aorta wall leading to a chronic increase in diameter and resulting in rupture. This is due to the lack of regeneration of elastic fibers and chronic proteolytic breakdown of elastic fibers within the aorta mediated by matrix metalloproteinases (MMPs), specifically MMP-2 and -9. Previous studies in our lab have shown cationic amphiphile-surface functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with doxycycline (DOX) to inhibit MMP activity and stimulate elastic matrix synthesis, effects we attributed to both low doses (< 10 mg/ml) of DOX released and independent effects of cationic amphiphile pendant groups on the NP surface. This promises application of these NPs to arrest or regress AAA growth since high oral DOX dosing inhibits new elastic matrix formation in the AAA wall and has undesirable side effects. In this study, we investigated feasibility of antibody-based active targeting of intravenously infused NPs to the AAA wall. Cathepsin K, a cysteine protease, is a biomarker for AAA and overexpressed in abdominal aortic aneurysm tissue making it an ideal target moiety. We have shown using a covalent conjugation method of modifying the surface of the NPs with a cathepsin K antibody resulted in a more robust antibody attachment which did not affect the DOX release profile. Cathepsin K expression was confirmed to be localized on the cell surface and utilizing cathepsin K Ab-conjugated NPs, we demonstrated an increased NP localization to the cathepsin K overexpressing cells in vitro and ex vivo. Importantly, the DOX-loaded NPs demonstrated pro-elastogenic and anti-proteolytic effects in aneurysmal smooth muscle cells supporting their use as regenerative therapies to arrest and regress AAA growth. Preliminary data has been collected indicating cathepsin K Ab-conjugated NP targeting to AAAs in elastase-injured rat models. The study outcomes support the feasibility of using cathepsin K Ab-conjugated NPs as a targeted therapy for elastic matrix regeneration in AAA tissue and will serve as a basis for already initiated follow up studies to assess NP biodistribution, in situ retention in the AAA wall, and safety as a function of time.

Committee:

Anand Ramamurthi, Ph.D. (Advisor); Nolan Holland, Ph.D. (Committee Member); Chandrasekhar Kothapalli, Ph.D. (Committee Member)

Subjects:

Biomedical Engineering

Ingels, Marcel LMechanics of Patellofemoral Maltracking in Total Knee Arthroplasty: A Finite Element Analysis
Master of Science, University of Toledo, 2016, Bioengineering
The patellofemoral joint is a complex joint that accounts for a large percentage of knee problems both in knee arthroplasty and in intact knee mechanics. In the United States alone, a 673% increase in primary total knee arthroplasty surgeries performed per year is projected to occur by 2030 (i.e., 3.48 million procedures). Consequently, the total revision rate per year is also projected to increase by 601% by 2030 (i.e., 268,200 revisions). Complication of the patellofemoral joint, associated with the patella maltracking, is one of the most common reasons for revisions in total knee arthroplasty and anterior pain of the intact knee. Thus, understanding patellofemoral maltracking mechanics and its associated risk factors is necessary. This study developed a validated finite element model of an intact knee to compare with instrumented knee patellar mechanics. The biomechanics of a maltracking patella are complex and have been shown to be associated with patellar subluxation, increased Q-angle, and increased external tibial rotation. These risk factors were applied individually and in combination to both an intact knee model and a knee instrumented with a total knee arthroplasty system to observe their effect on patellar mechanics. Thecombination of risk factors resulted in a worst-case maltracking model that was instrumented with a translating patellar implant with the goal of improving patellofemoral mechanics under maltracking conditions. The results of this study showed that the worst occurrence of patellar maltracking occurs because of a combination of various risk factors, such as patellar subluxation, increased Q-angle, and increased external tibial rotation for both intact and instrumented knees. Of these risk factors, the former contributes substantially more toward inducing non-physiological patellar mechanics than the latter two. Among the kinematic indicators for patellar maltracking in intact knees, medial/lateral patellar translation and tilt were ideal, whereas patellar rotation, although provided valuable insight on the patellofemoral joint kinematics, failed in showing any trend toward patellar maltracking. Among the kinematic indicators for patellar maltracking in instrumented knees, medial/lateral patellar translation was ideal, whereas patellar tilt and rotation, although provided valuable insight on the patellofemoral joint kinematics, failed in showing any trend toward patellar maltracking. Nevertheless, implant designers and clinicians should consider the rotation and tilt of the patella under various physiological conditions as design inputs for devices and conservative treatments. Lastly, the results of this study were used in designing a translating patellar implant that showed to reduce the risk of patellar maltracking, corroborating the value of aforementioned trends and kinematic indicators.

Committee:

Vijay Goel, PhD (Committee Chair); Anand Agarwal, PhD (Committee Member); Ronald Fournier, PhD (Committee Member)

Subjects:

Biomedical Engineering

Gawlik, Anna SComputer Extracted Nuclear Morphologic Features from Tumor and Benign Regions of H&E and Feulgen Stained Pathology Images Predict Biochemical Recurrence and Metastasis in Prostate Cancer Patients Post-Surgery
Master of Sciences (Engineering), Case Western Reserve University, 2017, Biomedical Engineering
Gleason score and nomograms are current methods used to evaluate prostate cancer (CaP) but are subject to inter-observer variability. The combination of computer extracted measurements from H&E and Feulgen stained CaP images could allow for improved characterization of disease appearance and enable accurate prediction of which patients are at risk for biochemical recurrence (BCR) and metastasis following radical prostatectomy. Nuclear morphology, architecture, and texture features were extracted from the tumor and tumor-adjacent benign regions of stained tissue microarray images of 260 CaP patients. A machine learning classifier was trained with the most predictive features identified on the training set to predict outcomes on the validation set. Clinical predictors of Gleason score and nomograms had a maximum prediction accuracy of 70.4% for BCR and 60% for metastasis on the validation set. The combination of H&E and Feulgen features yielded an accuracy of 95.63% for BCR and 70.8% for metastasis predictions.

Committee:

Anant Madabhushi (Advisor); Satish Viswanath (Committee Member); David Wilson (Committee Member); Robin Elliott (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

Prostate cancer; biochemical recurrence; metastasis; Feulgen; quantitative histomorphometry; image analysis

Babaie, ElhamSynthesis of Amorphous Alkaline Earth phosphate and its Applications in Orthopedics
Doctor of Philosophy, University of Toledo, 2016, Biomedical Engineering
The focus of this dissertation is synthesis and applications of amorphous alkaline earth phosphate such as magnesium-calcium phosphate and magnesium phosphate. Phosphates of alkaline earths such as calcium phosphates, are of great interest as bone replacement materials because they are biocompatible and resorbable in physiological conditions. As such, they have been studied for a long time. With growing research interest in magnesium alloys, magnesium phosphates have been gaining attention as a bone substitute material with comparable or in some cases, better properties than calcium phosphates. The compositional similarities between calcium phosphates (Ca Ps) and natural bone matrix prompted vigorous research activities in calcium phosphates. By comparison, research on magnesium-calcium phosphates are rare. Among the Ca P, amorphous calcium phosphates (ACP), have found applications as an important class of materials since their presence is important in commercial products such as plasma sprayed coatings on implants to self-setting CaP cements, or the fact that amorphous phase is as an intermediate phase in the synthesis of various crystalline phases of CaP. On the other hand, an understanding of the amorphous phases of magnesium phosphate or magnesium-calcium phosphate, or their transformation into their relevant crystalline phases is rare. For instance, it is shown that doping magnesium (small amount) in calcium phosphate can stabilize amorphous calcium phosphate prior to conversion to hydroxyapatite, However, not much information is available on amorphous magnesium phosphate as reports of synthesis of amorphous magnesium phosphate is scarce in the literature. Accordingly, this dissertation is broadly divided into five sub-sections. The first section reviews the state-of-the-art on processing of porous biomaterials. Porous biomaterials are an important class of materials and important goal of this research is to be able fabricate them in a cost-effective way. The second section discusses the synthesis and applications of amorphous magnesium-calcium phosphate, and amorphous magnesium phosphate as promising biomaterials in comparison to amorphous calcium phosphates or other relevant crystalline phases of calcium phosphates. The focus is on the mechanisms of formation and functional properties such as biocompatibility. In general, several methods have been proposed on the synthesis of amorphous phase, including synthesis from aqueous medium (wet route), using high energy processing or high temperatures (dry route) etc. Among them precipitation (wet route) was chosen in this study, because it is relatively simple and reproducible. Additionally, based on the method of the formation and experimental conditions (solution supersaturation, pH, etc.) different ratios of Ca/P, Mg/P, (Ca+Mg)/P ranging from 1 to 2 or even higher can be produced.The as-synthesized materials were characterized using Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR). In vitro studies were conducted on mouse osteoblasts, and SEM was used as the imaging methods. In the next of the work, the theme is to investigate the applications of amorphous magnesium-calcium phosphate, and amorphous magnesium phosphate as dense bodies (sintered bioceramic), as cement and also as porous cement scaffold in orthopedic applications. We show that amorphous magnesium phosphate, and amorphous magnesium-calcium phosphate can be produced through ethanol-assisted precipitation method. They are also shown to be biocompatible for relevant applications. The sinterability of amorphous magnesium-calcium phosphate and magnesium phosphate was studied. The results indicate that the amorphous phase of magnesium magnesium-calcium phosphates was able to transform into relevant crystalline phases upon sintering using microwave sintering technique. Next, the development of cement composite consisting of amorphous magnesium phosphate and hydrophilic poly vinyl alcohol (PVA) biopolymer, was carried. Finally, the ability of amorphous magnesium phosphate in fabrication of macroporous composite scaffold through gas-foaming technique was studied. Biodegradable Mg-particles were used as the porogen to produce macroporous structure. This method uses the fast corrosion kinetics of Mg to create macro pores in real time during the setting of the cement.

Committee:

Sarit Bhaduri (Committee Chair); Sarit Bhaduri (Advisor); Arunan Nadarajah (Committee Member); Vijay Goel (Committee Member); Mehdi Pourazady (Committee Member); Champa Jayasuriya (Committee Member)

Subjects:

Biomedical Engineering

Yang, DongqingMechanism and Mitigation of Biocorrosion by Nitrate Reducing Pseudomonas aeruginosa against Stainless Steel
Master of Science (MS), Ohio University, 2016, Biomedical Engineering (Engineering and Technology)
Biocorrosion, also known as microbiologically influenced corrosion (MIC), is the deterioration of metals and other materials due to the metabolic activity of microorganisms. MIC is a major problem in the oil and gas field and many other industries. It is caused by microbes in biofilms. In addition, biofilms have been recognized to be the cause of infections. It also occurs in medical devices and implants in the human body. Biocatalytic cathodic sulfate reduction (BCSR) theory illustrates the mechanism of MIC caused by sulfate reducing bacteria (SRB) from a bioenergetics perspective. BCSR can be adapted to explain MIC caused by other types of microbes such as nitrate reducing bacteria (NRB) in the form of biocatalytic cathodic nitrate reduction (BCNR). Pseudomonas aeruginosa is known as an opportunistic pathogen, which can grow as NRB using denitrification under anaerobic condition. In this work, the BCNR theory was supported by the starvation test using the wild-type P. aeruginosa (PAO1) in an anaerobic environment. The results suggested that NRB switched to elemental iron (Fe0) as an electron donor when there was a shortage of carbon sources under anaerobic condition. Compared to the control test, the highest weight loss (58% increase) and pit depth (more than twice deeper) were achieved under no carbon source condition. Extracellular electron transfer (EET) explains how electrons transfer from steel surface to sessile cells and cause MIC pitting corrosion of NRB. Two common electron mediators, riboflavin and flavin adenine dinucleotide (FAD), were tested to accelerate the electron transfer and enhance MIC in lab tests. The results showed that the maximum pit depth increased about 40% by adding either 10 ppm (w/w) FAD or 10 ppm riboflavin. Biocorrosion can occur in various fields and affect a variety of metal materials. Primarily due to their corrosion resistance, stainless steels have been widely used in the biomedical field. However, stainless steel is not antimicrobial and it may suffer MIC attack. The experimental data in this work showed that MIC pitting corrosion occurred in 304 type stainless steel caused by anaerobic PAO1 culture. A maximum pit depth of 3.91 µm was obtained after the 7-day culture. For the 14-day culture, more pits and larger pit diameters were observed. The maximum pit depth was 7.4 µm. D-amino acids have been investigated as antimicrobial enhancers to trigger biofilm disassembly under an antimicrobial stress. In order to inhibit and kill P. aeruginosa, a cocktail of D-tyrosine (D-tyr) and ciprofloxacin (CIP) was investigated in both the biofilm prevention test and the biofilm removal test using anaerobic PAO1 biofilms grown on carbon steel. The combined effect showed less weight loss and lower pit depth in the prevention test and achieved lower sessile cell counts in both the biofilm prevention test and the biofilm removal test. Compared to 30 ppm CIP alone treatment, there were one extra log reduction in the sessile cell count, an extra 24% reduction in the weight loss, an extra 17% decrease in the average maximum pit depth by using the cocktail of 30 ppm CIP + 2 ppm D-tyr in the biofilm prevention test.

Committee:

Tingyue Gu (Advisor); Douglas Goetz (Committee Member); Monica Burdick (Committee Member); Xiaozhuo Chen (Committee Member)

Subjects:

Biomedical Engineering; Chemical Engineering

Keywords:

microbiologically influenced corrosion; nitrate reducing bacteria; Pseudomonas aeruginosa; mitigation; stainless steel

Ramachandra, RakshitInjury and Impact Responses of the Abdomen Subjected to Seatbelt Loading
Doctor of Philosophy, The Ohio State University, 2016, Biomedical Engineering
Past research has shown that abdominal injuries account for nearly five percent of all injuries that occur during motor vehicle collisions (MVC) and rank in the top five compared to all body regions. In order to prevent injury to the abdomen, it is necessary to understand the mechanical response of the abdomen under various loading modes. While many studies have looked into mechanical responses of abdomen by subjecting human surrogates to impact conditions such as rigid-bar, seatbelt and airbags, an agreeable correlation between abdominal injuries and injury metric that is not readily available. Such a scenario translates directly to the lack of an injury predictive biofidelic abdomen such as in the Hybrid III (H-III) anthropomorphic test device (ATD), which is currently in use for crash safety regulation. With the rise in use of finite element (FE) models to mimic real world crash scenarios, it is necessary to correlate the virtual human models to injury response and tolerance data from laboratory tests before using them to investigate occupant safety. To address the concerns described above, this study first identified the frequency and severity of abdominal injuries in MVCs with updated case years using the National Automotive Sampling System (NASS) Crashworthiness Data System (CDS) database. Then, the response of post mortem human surrogates (PMHS) was investigated using a simplified and controllable method such as belt loading to the abdomen. The same fixture was employed to test the current state of art abdomen inserts for ATDs to understand their responses to similar loading. A full body human FE model from the Global Human Body Models Consortium (GHBMC) was subjected to seatbelt loading similar to the experimental setup to identify the gaps between experimental and analytical outcomes. Based on the NASS analysis, nearly 18,000 adult occupants sustain abbreviated injury scale (AIS) greater than two abdominal injuries in frontal and side crashes, with more than half of these occurring in frontal crashes alone. An increase in the risk of AIS2+ injury to abdominal organs was observed with increasing crash severity, however the risk remained fairly constant across all age groups. While belted occupants were at lower risk of abdominal injuries compared to the unbelted occupants, it is unclear if the lap belt penetrating into the abdomen was the source of injury for belted occupants. When analyzing the risk of injuries to solid organs such as spleen and liver, the odds of AIS2+ injury occurring to these organs is more when the occupant also sustains AIS2+ rib fractures. However, the occurrence of solid organ injuries in the absence of rib fractures highlights the need for a separate injury criteria for abdomen which does not exist at this time. A total of seven unembalmed PMHS, with an average mass and stature of 71 kg and 174 cm respectively were subjected to belt loading using a seatbelt pull mechanism, with the PMHS seated upright in a free-back configuration. A pneumatic piston pulled a seatbelt into the abdomen at the level of umbilicus with a nominal penetration speed of 4.0 m/s. Pressure transducers were placed in the re-pressurized abdominal vasculature, including the inferior vena cava (IVC) and abdominal aorta, to measure internal pressure variation during the event. Jejunum tear, colon hemorrhage, omentum tear, splenic fracture and transverse processes fracture were identified during post-test anatomical dissection. Peak abdominal forces ranged from 2.8 to 4.7 kN. Peak abdominal penetrations ranged from 110 to 177 mm. A force-penetration corridor was developed from the PMHS tests in an effort to benchmark ATD biofidelity. Peak aortic pressures ranged from 30 to 104 kPa and peak IVC pressures ranged from 36 to 65 kPa. A pressure based abdominal injury risk function (IRF) was developed and abdominal injury criteria such as vascular P¿max and Pmax P¿max, that exhibited a strong relationship with abdominal injuries, are proposed. Using the same test apparatus, Hybrid III 50th male ATD retrofitted with rate-sensitive gel-filled abdomen developed by Rouhana et al. (2010), Thor NT ATDs with standard abdomen and a prototype abdomen proposed by Hanen et al. (2012) were tested. Force-penetration results were compared to the PMHS response. The peak pressure and P¿max values of the Thor NT abdomen were compared to the values from PMHS tests. The retrofitted Hybrid III had a peak force of 3.5 kN with a peak penetration of 95 mm under the same input condition as PMHS tests. Thor NT with standard abdomen had a peak force of 5 kN with peak penetration of 100 mm. Thor NT retrofitted with prototype abdomen had an average peak force and penetration of 4.6 kN with 85 mm respectively. The pressure values from the prototype abdomen ranged from 149 to 165 kPa. The force-penetration from the Thor NT abdomen tests show a similar initial trend as the PMHS test, although peak force occurred at a lesser penetration compared to the PMHS. The retrofitted Hybrid III displayed a stiff initial response followed by unloading sooner compared to the Thor NT. The P¿max values calculated in pressure cylinders of the Thor NT ATD prototype abdomen corresponded to a 70% risk of abdominal injury based on the IRF developed in the PMHS studies.

Committee:

John Bolte IV (Advisor)

Subjects:

Biomedical Engineering

Keywords:

Abdomen, Seatbelt, Vascular pressure, Motor vehicle crashes, Thor NT, NASS

Mollica, Molly Y.DNA Origami Breadboard: A Platform for Cell Activation and Cell Membrane Functionalization
Master of Science, The Ohio State University, 2016, Mechanical Engineering
Structural DNA Nanotechnology (“DNA origami”) techniques have enabled the design and synthesis of complex 3D nanostructures with dynamically controllable features that exploit molecular self-assembly principles. Any component that can be conjugated to an oligonucleotide (oligo) can be attached to a DNA nanostructure at a specific location and quantity with nanometer resolution. This includes some fluorescent dyes, quenchers, peptides, RNA, steroids, vitamins, and, by extension, all molecules capable of biotinylation. A DNA origami “breadboard” with 34 strategically located attachment points can therefore be functionalized with a wide variety of components and used for a multitude of purposes. In this thesis, the design, fabrication, purification, characterization, and application of a 68 x 25 x 6 nanometer honeycomb lattice DNA nanostructure will be presented for use in two distinct functions. In the first, a biotinylated antibody was added to the platform and used to better mimic a cell-to-cell receptor-ligand interaction with tunable antibody quantity, location, and flexibility (i.e. range of motion). This led to determination that ligand flexibility, which can be controlled using DNA origami, influences strength of cell activation. In the second, cholesterol-modified oligonucleotides were added to cells and used to anchor the nanostructures onto the cell surface. The ability to integrate DNA origami nanostructures into a cell membrane can enable a wide variety of applications such as a intracellular force sensing, programmed cell-cell adhesion, or triggered recruiting of biomolecules from solution.

Committee:

Carlos Castro (Advisor); Jonathan Song (Committee Member)

Subjects:

Biomechanics; Biomedical Engineering; Cellular Biology; Mechanical Engineering

Keywords:

DNA nanotechnology; DNA origami; DNA breadboard; cell membrane; receptor-ligand;

Chopra, PoojaFabrication of Multi-Parallel Microfluidic Devices for Investigating Mechanical Properties of Cancer Cells
Master of Science (MS), Ohio University, 2016, Physics and Astronomy (Arts and Sciences)
There is evidence that mechanical properties and deformability can be used as a biomarker to distinguish between healthy and cancerous cells. A number of biophysical techniques such as atomic force microscopy (AFM), and optical tweezers have been used to measure the mechanical properties of cancer cells. Multi-parallel microfluidic devices can be used as a high throughput method to study the deformation of cells. We hypothesize that difference in cell entry time and passage through the channels can be used to distinguish cancer cells from the healthy cells as well as to distinguish differences between cancer cell lines. We fabricated a multi-parallel microfluidic device using photolithography and channels surfaces were coated with bovine serum albumin (BSA) to minimize non-specific adhesion. The design has a single entry and exit to mimic micropipette experiments. The channel widths can be chosen either to deform the cell membrane or to deform both the cell membrane cortex and the cell nucleus. This work lays the foundation for the development of microfluidic devices which can subsequently be used in the detection of mechanical properties of cancer cells.

Committee:

David Tees, Dr (Advisor); Sergio Ulloa, Dr (Committee Chair); Hee-Jong Seo, Dr (Committee Member)

Subjects:

Biomedical Engineering; Biomedical Research; Biophysics; Physics

Keywords:

microfluidic device; microchannel; fabrication of microfluidic device; mechanical properties of cancer cell; parallel microfluidic; photolithography

Short, Aaron RHydrogels: Use and Function in Cancer Migration, Infiltration, and Drug Delivery
Doctor of Philosophy, The Ohio State University, 2016, Biomedical Engineering
Diseases that arise in the central nervous system (CNS) (i.e., glioblastoma) are not only devastating, but as a result of the nature and overall physiology of the CNS, are difficult to assess and treat. In order to better treat diseases like glioblastoma, a form of brain cancer, it is imperative to obtain a greater understanding of the underlining mechanisms responsible for its progression. GBM is particularly deadly because of anatomical limitations in treatment by radiation and surgery, and the eventual development of resistance to chemo-radiation therapy, which results in a highly migratory phenotype. Thus, understanding GBM migration could lead to improved therapies. In vivo models of cell migration and tumor growth allow for the most accurate representation of the physiological extracellular matrix (ECM). Unfortunately, short of expensive genetically altered animals, they have a limited capacity to study individual protein effects, which is crucial in determining how cells interact with the microenvironment during metastasis. To this end, substantial research has been performed to develop in vitro assays that allow for accurate recapitulation of neural microenvironment properties (i.e. physical, chemical, and mechanical), while allowing for individual components to be analyzed. To enhance simple two-dimensional co-cultures systems; a topographical biomimetic was created with electrospun nanofibers of poly (e-caprolactone) (PCL) for use as an in vitro assay. This approach was used to assess the effects of cancerous glioblastoma cells on healthy astrocytes and vice versa. Analysis of the co-culture systems, suggests that the presence of glioma-produced ECM was a primary factor in astrocyte activation, whereas astrocytes increased glioblastoma migration rates. Interestingly, astrocyte-conditioned medium promoted glioma migration, whereas culture in the presence of fixed astrocytes was antagonistic to migration. In addition to cancer cell migration, these in vitro models show promise in achieving a better understanding in neural stem cell differentiation. Through a simple modulation of fiber diameter, morphology and migration of neural stem cells can be altered during differentiation. However, whereas these complex two-dimensional assays (i.e., electrospun nanofibers) are a large improvement from simple two-dimensional assays, they still fall short of the complex three-dimensional environment seen in vivo. For example, hyaluronic acid (HA) is a common protein in the CNS that is upregulated in glioblastoma tumors; creating a gradient of HA as cells leave the tumor microenvironment. Therefore, we synthesized hydrogels containing both HA and collagen to mimic physiological conditions. Interestingly, intercalated hydrogels of HA and fibril collagen showed an agnostic effect to cell migration as HA concentration increased. This raises the curious question; with glioblastoma being so highly migratory, how does a protein that is upregulated in the tumor microenvironment inhibit migration in vitro? To answer this question, new tools are needed. Through gel digestion and western blot analysis, protein quantification can be achieved. However, observing the spatial distribution of these proteins via immunofluorescence in hydrogel constructs can be difficult because of their high refractive properties. Typical methods use cryosectioning techniques to create thin hydrogel sections for staining. Unfortunately, this method creates disruption within the collagen matrix, limiting its use in understanding cell-ECM interactions. Utilizing histological processing techniques for tissues, we developed new processing methods to attenuate these artifacts, preserving the collagen matrix and permitting assessment of cell-ECM interactions. Ultimately developing novel assays that allow for the incorporation of multiple cues, while creating a physiologically relevant microenvironment, is crucial in further understanding cell migration in vivo. In this dissertation, we have sought to develop such models to elucidate the underlying mechanisms of brain tumor cell migration. In addition, these models may ultimately have broader applications for other cancers and within tissue engineering and regenerative medicine.

Committee:

Jessica Winter (Advisor); Jose Otero (Committee Member); Heather Powell (Committee Member); Leight Jennifer (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

Tissue Engineering; Biomaterials; Oncology; Biosignaling; Glioblastoma

Zaidi, Syed Anwar HyderOptical Redox Imaging of Metabolic Activity
Master of Science in Biomedical Engineering (MSBME), Wright State University, 2016, Biomedical Engineering
Fluorescence imaging can be used to determine tissue metabolism, which is an indication of the cellular functionality. Metabolic contrast is useful for the early detection of several medical conditions such as cancer, diabetes, lung diseases etc. This study aims to use fluorescence imaging to quantify NADH and FAD, which are cellular metabolic indicators. A parameter known as Redox ratio, can be used to study metabolic state of several tissue types and disease states. To quantify the Redox ratio, three fluorescence imaging systems were optimized to measure the fluorescence signal from NADH and FAD. The first system was a camera based model suitable for laboratory and clinical settings. The second and third were compact versions of the same instrument. The systems were characterized and brain cancer cells were measured using the camera-based system and the compact model, which resulted in a similar Redox ratio.

Committee:

Ulas Sunar, Ph.D. (Advisor); Jaime Ramirez-Vick, Ph.D. (Committee Member); Debra Mayes, Ph.D. (Committee Member)

Subjects:

Biomedical Engineering; Biomedical Research; Biophysics; Electrical Engineering; Medical Imaging; Optics

Keywords:

Fluorescence imaging; cancer diagnosis; compact devices; wireless devices; optical imaging

Bootsma, Katherine JeanThe Development of 3D Printable Materials
Master of Science, Miami University, 2016, Chemical, Paper & Biomedical Engineering
An interpenetrating polymer network (IPN) is a material that possesses unique physical and mechanical properties. These unique properties give rise to the use of IPNs in a variety of applications including drug delivery, tissue engineering scaffolds, and as actuators in soft robotics. This thesis reports two separate applications of IPNs where 3D printing could prove useful. The first study focuses on the use of an alginate-polyacrylamide IPN hydrogel as a potential material for use in a medical simulator. The chemistry of a previously reported biomimetic IPN was altered so that 3D printing could be achieved. The elastic and viscoelastic behaviors of the 3D printed IPNs were quantified and found to be on the range of various biological tissues. The second study focuses on the development of a PVDF-poly(glycidyl methacrylate-co-methyl methacrylate) IPN as a separator membrane in a flexible lithium ion battery. A second polymer network was added to a preexisting separator formulation to create a semi-IPN. This separator membrane was characterized with dissolution tests, tensile mechanical tests, and rheology.

Committee:

Jessica Sparks (Advisor); Jason Berberich (Advisor); Dominik Konkolewicz (Committee Member)

Subjects:

Biomedical Engineering; Chemical Engineering

Keywords:

3D printing; hydrogel; IPN; medical simulation

Keshav, ArvindTRACKING AN ELECTRICALLY SILENT SOURCE IN THE HIPPOCAMPUS USING A CALCIUM-SENSITIVE FLUORESCENT DYE
Master of Sciences (Engineering), Case Western Reserve University, 2016, Biomedical Engineering
Analysis of the neural activity in the hippocampus in the presence of epileptogenic agents shows fast-moving spikes sensitive to N-Methyl-D-Aspartate (NMDA) coming from a putative electrically silent source moving at a slower speed and difficult to track with standard fluorescence methods. Advances in imaging technology have allowed for millisecond-resolution mapping of the changes in fluorescence with high spatial resolution. In this study, the presence of this electrically silent focus was revealed by mapping the increase in intracellular calcium using the calcium-sensitive fluorescent dye Oregon Green 488 BAPTA-1 (OGB-1). Results indicate that the focus and its propagation can indeed be tracked using OGB-1, with a mean propagation velocity, obtained by cross-correlation calculations, of 0.0036 ± 0.0009 m/s, well within the predicted range for the putative source from other indirect measurements. Additionally, we tested in vitro the hypothesis that the propagation of this focus was independent of the NMDA-sensitive spikes it generates. The NMDA blocker introduced prevented the generation of spikes, but the movement of the focus was unaffected. The mean propagation velocity was 0.0035 ± 0.001 m/s and t-test results showed no significant difference in propagation speeds with and without the NMDA blocker. Together, these results indicate that the electrically silent focus is indeed the source of the spikes and relies on a different unknown mechanism of propagation. A possible mechanism of propagation is through the diffusion of potassium. However, the speed of the potassium wave was found to be significantly lower than that observed for our source (P<0.0001). These results indicate the presence of a novel calcium wave in the hippocampus propagating through pyramidal cells and capable of generating NMDA-sensitive spikes.

Committee:

Dominique Durand (Advisor); Jeffrey Capadona (Committee Member); Andrew Rollins (Committee Member)

Subjects:

Biomedical Engineering; Biomedical Research

Keywords:

epilepsy; electrically silent source; calcium-sensitive fluorescent dyes; NMDA

Poon, Chien SingEarly Assessment of Burn Severity in Human Tissue with Multi-Wavelength Spatial Frequency Domain Imaging
Master of Science in Biomedical Engineering (MSBME), Wright State University, 2016, Biomedical Engineering
Burn injuries such as thermal burns, which are caused by contact with flames, hot liquids, hot surfaces, and other sources of high heat as well as chemical burns and electrical burns, affects at least 500,000 people in the United States, to which 45,000 of them require medical treatment and 3,500 of them result in death. It has also been reported that in the United States alone, fire results in a death approximately every three hours and an injury every 33 minutes. Early knowledge about burn severity can lead to improved outcome for patients. In this study, the changes in optical properties in human skin following thermal burn injuries were investigated. Human skin removed during body contouring procedures was burned for either 10 or 60 seconds using a metal block placed in boiling water. Multi-wavelength spatial frequency domain imaging (SFDI) measurements were performed on each sample and the optical properties (absorption and scattering parameters) were obtained at each wavelength. Multi-wavelength fitting was used to quantify scattering parameters, and these parameters were compared to histologic assessments of burn severity. Our results indicate substantial changes in optical parameters and changes, which correlate well with respect to burn severity. This study shows the characterization of thermal burn injury on human skin ex vivo by using the optical method of SFDI with high sensitivity and specificity. Due to more challenging conditions of layered skin structures with differing thickness in humans, ongoing work tackles combining high-resolution ultrasound imaging with SFDI for more accurate quantification of optical properties during in vivo clinical studies.

Committee:

Ulas Sunar, Ph.D. (Committee Chair); Ping He, Ph.D. (Committee Member); Jeffrey Travers, M.D. Ph.D. (Committee Member)

Subjects:

Biomedical Engineering; Biomedical Research; Biophysics; Cellular Biology; Engineering; Medical Imaging; Optics; Physics

Keywords:

Optical Imaging; Medical Imaging; burn wound assessment; diagnosis; fluorescence; multispectral imaging; optical properties; quantitative assessment; skin burn; spatial frequency domain imaging; system; tissue scattering; wounds

Swaminathan, GaneshEvaluation Of Adult Stem Cell Derived Smooth Muscle Cells For Elastic Matrix Regenerative Repair
Doctor of Philosophy, University of Akron, 2016, Biology
Elastic fibers (EFs), containing elastin protein are the major structural extracellular matrix component of the aorta wall that imparts it stretch and recoil properties. Following injury stimuli to the aorta wall, EFs are disrupted by chronically overexpressed proteolytic enzymes. This leads to loss of wall elasticity, and vessel bulging to form rupture-prone abdominal aortic aneurysms (AAAs). AAA growth arrest or regression to a healthy state requires restoration of elastin homeostasis in the aorta wall which is limited by very poor elastogenicity of adult and aneurysmal vascular smooth muscle cells (SMCs). Based on their purported role in developmental elastogenesis, we explored use of stem cell-derived SMCs in therapeutically augmenting elastogenesis in the AAA wall. In study 1, we differentiated adult rat bone marrow mesenchymal stem cells (BM-MSCs) into SMCs (BM-SMCs), demonstrated their robust capacity for elastin synthesis and significant pro-elastogenic effects on rat aneurysmal SMCs (EaRASMCs). In study 2, we sought to identify phenotypic subtypes of derived BM-SMCs that are most elastogenic. BM-SMCs generated in low glucose (3.1g/L) and high serum (10% v/v) media containing transforming growth factor-beta (TGFß) and platelet-derived growth factor (PDGF) exhibited both synthetic and contractile properties that constituted their enhanced synthesis of elastin precursors, elastic matrix, and the desmosine crosslinks within the elastic matrix. In study 3, these BM-SMCs were co-cultured with EaRASMCs within 3-D collagen constructs. We observed significant increases in elastic matrix synthesis and fiber formation relative to EaRASMCs alone or in co-culture with healthy rat aortic SMCs. Proteomic analysis indicated presence of several unique and upregulated elastogenic growth factors in BM-SMC secretome. In study 4, we sought to render the BM-SMCs magnetically mobile for efficient delivery to the aorta wall for regenerative cell therapy. We showed that incorporating super paramagnetic iron oxide nanoparticles (SPIONs) within BM-SMCs imparted them significant magnetic responsiveness in an externally-applied magnetic field and not adversely impact their beneficial properties. We showed significantly higher uptake and retention of SPION-labeled BM-SMCs within matrix-injured arteries perfused ex vivo. Overall, our work has established an alternative elastogenic cell source that is promising towards in situ elastic matrix regenerative therapy.

Committee:

Anand Ramamurthi , PhD (Advisor); Francis Loth, PhD (Committee Chair); Peter Niewiarowski , PhD (Committee Co-Chair); Vinod Labhasetwar, PhD (Committee Member); Rolando Ramirez, PhD (Committee Member)

Subjects:

Biology; Biomedical Engineering; Biomedical Research

Keywords:

Tissue engineering, elastic matrix, regenerative therapy, smooth muscle cells, stem cells

Walia, PiyushThe Effect of Combined Bony Defects on the Anterior Stability of the Glenohumeral Joint and Implications for Surgical Repair
Doctor of Engineering, Cleveland State University, 2015, Washkewicz College of Engineering
The combined defects of the glenoid and humeral head defects are often associated with recurrent anterior instability. Past studies have only investigated the effects of isolated humeral head or glenoid defects. A cadaveric model was developed to investigate the effect of combined defects. Moreover, two different finite element models were developed to validate against the experimental data. It was hypothesized that combination of smaller sizes of the two defects would reduce the glenohumeral joint’s stability. Furthermore, it was hypothesized that the instability due to humeral head defect will be dependent on the arm position but this won’t be the case for the glenoid defect. Also, it was believed that both specimen-specific and population-based models will validate against the experimental data. Different sets of simulation were run with both isolated and combined defects to analyze the reaction forces and calculate distance to dislocation. The experiments were performed with displacement control under a 50N compressive load. The results from the study predicted a statistical model that explained the direct correlation between the anterior stability of glenohumeral joint and the size of the defect. It was found that with the increase in size of the defect, the distance to dislocation decreased. It was determined that a combination of 10% glenoid defect with a 19% humeral head defect resulted in lower stability (p<0.05) than that of an isolated 20% glenoid defect. Results from finite element analysis showed that both specimen-specific and population-based models were similar to cadaveric model.

Committee:

Stephen Fening, Ph.D. (Committee Chair); Antonie van den Bogert, Ph.D. (Advisor); Anthony Miniaci, M.D., F.R.C.S.C. (Committee Member); Morgan Jones, M.D., M.P.H (Committee Member); Ahmet Erdemir, Ph.D. (Committee Member); Brian Davis, Ph.D. (Committee Member)

Subjects:

Biomechanics; Biomedical Engineering; Biomedical Research; Design; Engineering; Experiments; Mathematics; Pathology; Sports Medicine

Keywords:

Shoulder, Glenohumeral Joint, Anterior Instability, Combined Bone Defects, Hill-Sachs Defect, Bony Bankart Lesion, Humeral Head Bone Loss, Bipolar Defects, Concavity Depth, Stability Ratio

Warner, Holly E.Optimal Design and Control of a Lower-Limb Prosthesis with Energy Regeneration
Master of Science in Mechanical Engineering, Cleveland State University, 2015, Washkewicz College of Engineering

The majority of amputations are of the lower limbs. This correlates to a particular need for lower-limb prostheses. Many common prosthesis designs are passive in nature, making them inefficient compared to the natural body. Recently as technology has progressed, interest in powered prostheses has expanded, seeking improved kinematics and kinetics for amputees. The current state of this art is described in this thesis, noting that most powered prosthesis designs do not consider integrating the knee and the ankle or energy exchange between these two joints. An energy regenerative, motorized prosthesis is proposed here to address this gap.

After preliminary data processing is discussed, three steps toward the realization of such a system are completed. First, the design, optimization, and evaluation of a knee joint actuator are presented. The final result is found to be consistently capable of energy regeneration across a single stride simulation. Secondly, because of the need for a prosthesis simulation structure mimicking the human system, a novel ground contact model in two dimensions is proposed. The contact model is validated against human reference data. Lastly, within simulation a control method combining two previously published prosthesis controllers is designed, optimized, and evaluated. Accurate tracking across all joints and ground reaction forces are generated, and the knee joint is shown to have human-like energy absorption characteristics. The successful completion of these three steps contributes toward the realization of an optimal combined knee-ankle prosthesis with energy regeneration.

Committee:

Daniel Simon, Ph.D. (Committee Chair); Hanz Richter, Ph.D. (Committee Member); Antonie van den Bogert, Ph.D. (Committee Member)

Subjects:

Biomedical Engineering; Engineering; Mechanical Engineering; Robotics

Zheng, ZijieIN SITU FORMING PHOTODEGRADABLE HYDROGEL FOR CONTROLLED DELIVERY OF siRNA
Master of Sciences, Case Western Reserve University, 2015, Biomedical Engineering
Cells adapt themselves to the dynamic extracellular environment by responding to numerous signal stimuli. Strategies for engineering stimulus-responsive biomaterials as drug delivery vehicles may mimic this responsiveness and allow for spatiotemporal control over drug delivery. Short interfering RNA (siRNA) can inhibit specific gene expression by cleaving complementary mRNA molecules, which may be useful when presented in a stimulus-responsive manner. Here, a photodegradable hydrogel system was developed for siRNA delivery, and the release of siRNA complexed with poly(ethyleneimine) (siRNA/PEI) from photodegradable hydrogels was tailored by the trigger of UV exposure. Photodegradable poly (ethylene glycol)-based hydrogels containing siRNA/PEI complexes have been successfully fabricated, and light-triggered release of siRNA and gene-silencing abilities of released siRNA in cells cultured in monolayer has been shown using green fluorescent protein as a reporter. Future work can extend this platform technology to temporally control biologically relevant processes in an “on-demand” manner.

Committee:

Eben Alsberg (Advisor); Zheng-Rong Lu (Committee Member); Nicole Steinmetz (Committee Member)

Subjects:

Biomedical Engineering

Keywords:

siRNA, photodegradable, hydrogel, controlled release

Next Page