Biomedical Engineering and Bioengineering Commons^™

Novel Injectable Plga-Peg-Plga Self-Assembled Hydrogels For The Extended And Controlled Release Of Dna Nanocarriers To Prevent Secondary Cataracts, Laura L. Osorno

Theses and Dissertations

Cataracts are the second leading cause of blindness worldwide. There are over 20 million cataract surgeries each year, and these cases are expected to double within the next ten years. Over 40% of adults and nearly all children develop secondary cataracts, or posterior capsule opacification (PCO), following cataract surgery. Currently, Nd:YAG laser therapy is used to treat PCO; however, laser therapy is not available worldwide and treatment may have adverse effects on surrounding ocular tissues. Thus, there is a considerable unmet need for more efficacious and convenient treatments to prevent PCO.

Injectable, stimuli-responsive gels were designed using poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)) …

Designing Silk Protein-Based Composite Materials With Tunable Heat Transfer And Magnetic Properties, Ye Xue

Theses and Dissertations

Renewable and biocompatible silk protein materials with desired physical properties show promising applications in biomedical field. In this work, a set of protein-based composites with desired thermal and magnetic properties, enhanced by the appropriate distribution of nanofillers in the protein matrix in both 2D-film and 1D-fiber forms was investigated. Results indicate that secondary structures of silk protein materials regenerated by a formic acid-calcium chloride method are different from those of their respective natural silk fibers. Intramolecular beta-sheet structures were found to dominate these silk films, causing these regenerated samples to be water-insoluble but more flexible than traditional silk films with …

Study And Characterization Of Conductive Elastomers For Biomedical Applications, Hadis Gharacheh

Theses and Dissertations

Health issues have always been one of humankind's biggest challenges. Over the last century, there has been significant and monumental progress in health and biomedical science, with the end goal of alleviating and eliminating illnesses and ailments. For developing biomedical devices, polymers and elastomers group among other types of biomaterials have been highlighted to be used due to high flexibility, stability, biocompatibility, and mechanical and rheological characteristics. In this work, the characterization of acrylated poly glycerol_sebacate (PGSA) polymer conjugated with bio ionic liquid (BIL) was investigated. Results showed high biocompatibility, high printability with tunable mechanical, adhesive, and conductivity properties. For …

Toward Precision Medicine With Nanopore Technology, Trang Andrea Vu

Theses and Dissertations

Currently, when patients are diagnosed with cancer, they often receive a treatment based on the type and stage of the tumor. However, different patients may respond to the same treatment differently, due to the variation in their genomic alteration profile. Thus, it is essential to understand the effect of genomic alterations on cancer drug efficiency and engineer devices to monitor these changes for therapeutic response prediction. Nanopore-based detection technology features devices containing a nanometer-scale pore embedded in a thin membrane that can be utilized for DNA sequencing, biosensing, and detection of biological or chemical modifications on single molecules. Overall, this …

System Reliability Analysis Of The Scoliosis Disorder., Fatemeh Nouri, Seyed Hooman Ghasemi, Ji Yun Lee

Henry M. Rowan College of Engineering Departmental Research

BACKGROUND: Scoliosis is a spine abnormal deviation, which is an idiopathic disorder among children and adolescents. As a matter of the fact, distribution of loads on the patient's spine and load-carrying capacity of the vertebral column are both random variables. Therefore, the probabilistic approach may consider as a sophisticated method to deal with this problem.

METHOD: Reliability analysis is a probabilistic-based approach to consider the uncertainties of load and resistance of the vertebral column. The main contribution of this paper is to compare the reliability level of a normal and scoliosis spinal. To do so, the numerical analyses associated with …

Low-Cost Solid State Nanopore Biosensing Technology Towards Early Disease Detection, Julian Bello

Theses and Dissertations

Solid-state nanopore based biosensors are cost effective, high-throughput engines for single molecule detection of biomolecules, which is useful for detecting epigenetic modifications on DNA; one of these being the potentially cancerous hypo, or hypermethylation of CpG islands. Despite its immense potential in the realm of disease diagnostics, nanopore detection as it stands faces various limitations that inhibit it from widespread commercial use. These include the complex method of solid-state nanopore fabrication, fast DNA translocations through the pore causing poor resolution, and poor signal to noise ratio. The following work aims to improve the efficacy of the solid-state nanopore biosensing platform …

Fabrication Of Vascularized Scaffolds For The Treatment Of Spinal Cord Injury, Paul P. Partyka

Theses and Dissertations

The overall goal of the research presented here is to evaluate the efficacy of transplanting scaffolds containing central nervous system vasculature to repair spinal cord injury. There are three major phases of this effort: development of a three-dimensional model of central nervous system vasculature, transplantation of a pre-vascularized scaffold and optimization of the biomaterial used to deliver vasculature to the injured spinal cord. This research has produced the first ever compliant, three-dimensional (3D) blood-brain barrier (BBB) vessel. In order to create vascularized scaffolds appropriate for transplantation into a rat model of spinal cord injury, techniques to fabricate and spatially pattern …

Bioadhesive Hydrogel Composite Cell Carrier For The Repair Of The Degenerated Intervertebral Disc, Thomas Richard Christiani

Theses and Dissertations

Lower back pain (LBP) affects the worldwide population and can be attributed to the degeneration of the intervertebral disc (IVD). The IVD is composed of a central nucleus pulposus (NP), a peripheral annulus fibrosus (AF), and adjacent cartilage endplates (CEPs). IVD degeneration is characterized by proteoglycan loss, tissue dehydration, and decreased hydrostatic pressure. In this work, the use of an injectable bioadhesive hydrogel composite for replacement of the degenerated NP was investigated.

Results indicate that the composite exhibits similar mechanical properties to the NP, adheres to AF tissue, and supports encapsulated mesenchymal stem cell (MSC) differentiation toward an NP-like phenotype …

Diurnal Patterns Of Gene Expression In The Dorsal Vagal Complex And The Central Nucleus Of The Amygdala - Non-Rhythm-Generating Brain Regions., Mary M Staehle, Sean O'Sullivan, Rajanikanth Vadigepalli, Kate F Kernan, Gregory E Gonye, Babatunde A Ogunnaike, James S Schwaber

Henry M. Rowan College of Engineering Departmental Research

Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications …

Effects Of Fiber Density And Strain Rate On The Mechanical Properties Of Electrospun Polycaprolactone Nanofiber Mats., Adriano A Conte, Katie Sun, Xiao Hu, Vincent Beachley

Henry M. Rowan College of Engineering Departmental Research

This study examines the effects of electrospun polycaprolactone (PCL) fiber density and strain rate on nanofiber mat mechanical properties. An automated track collection system was employed to control fiber number per mat and promote uniform individual fiber properties regardless of the duration of collection. Fiber density is correlated to the mechanical properties of the nanofiber mats. Young's modulus was reduced as fiber density increased, from 14,901 MPa for samples electrospun for 30 s (717 fibers +/- 345) to 3,615 MPa for samples electrospun for 40 min (8,310 fibers +/- 1,904). Ultimate tensile strength (UTS) increased with increasing fiber density, where …

Microarray Embedding/Sectioning For Parallel Analysis Of 3d Cell Spheroids., Jonathan Gabriel, David Brennan, Jennifer H Elisseeff, Vincent Beachley

Henry M. Rowan College of Engineering Departmental Research

Three-dimensional cell spheroid models can be used to predict the effect of drugs and therapeutics and to model tissue development and regeneration. The utility of these models is enhanced by high throughput 3D spheroid culture technologies allowing researchers to efficiently culture numerous spheroids under varied experimental conditions. Detailed analysis of high throughput spheroid culture is much less efficient and generally limited to narrow outputs, such as metabolic viability. We describe a microarray approach that makes traditional histological embedding/sectioning/staining feasible for large 3D cell spheroid sample sets. Detailed methodology to apply this technology is provided. Analysis of the technique validates the …

The Impact Of Patient-Specific Vascular Structure On Localized Cooling In The Human Heart, Nathan Paul Spangenberg

Theses and Dissertations

Acute Myocardial Infarction (AMI) is the leading cause of worldwide death and disability, and approximately 720,000 Americans will experience an AMI in 2018. Studies have shown that rapid hypothermia therapy (<35°C) before reperfusion in patients with AMI can reduce infarct size by 37%. Localized therapeutic hypothermia has proven the potential to cool heart tissue rapidly following AMI, 3°C in 5 minutes. Using Materialise Mimics digital imaging software and the finite volume method we analyzed temperature distributions in six patient-specific left main coronary artery (LMCA) models. A mock circulatory loop was used to determine the exiting temperatures of a standard 7 Fr catheter to feed into our model with flow rates ranging from 29.2 ml/min to 68.85 ml/min. Our work showed that therapeutic hypothermia (TH) temperatures were evident at the outlets of three out of all six heart models, which varied in each left anterior descending (LAD) and left circumflex (LCX) artery depending on flowrate. Results of this study indicate that biovariability in patient-specific vascular structures significantly impacts therapeutic hypothermia (TH) treatment methods. These results indicate that further research is needed to examine more accurate physiological effects, such as pulsatile flow and vessel wall thickness. Future models will be used to provide insight to guide more efficient TH device designs and operation parameters to optimize patient outcomes following AMI.

Initial Development Of A Prototype Sensor Testbed For Fetal Monitoring, Christian Beauvais

Theses and Dissertations

The objective of this research is to design and manufacture a device that exhibits some of the bio-physiological signals relevant to fetal health monitoring. Currently, limited options exist for testing the performance of monitoring devices such as the tocodynamometer (TOCO) and electrocardiograph (ECG) that measure the bio-physiological signals of a woman and her fetus. Sensor designers need ways of generating and acquiring signals that do not carry the ethical burden of human testing. The development of such a device, as considered in this work, may involve using muscle wire or an inflatable tube as prospective foundations for simulating uterine contraction. …

Inverted Cone Convolutional Neural Network For Deboning Mris, Oliver John Palumbo

Theses and Dissertations

Data plenitude is the power but also the bottleneck for data-driven approaches, including neural networks. In particular, Convolutional Neural Networks (CNNs) require an abundant database of training images to achieve a desired high accuracy. Current techniques employed for boosting small datasets are data augmentation and synthetic data generation, which suffer from computational complexity and imprecision compared to original datasets. In this thesis, we intercalate prior knowledge based on the temporal relation between the images in the third dimension. Specifically, we compute the gradient of subsequent images in the dataset to remove extraneous information and highlight subtle variations between the images. …

In Vitro Evaluation Of 3d Printed Polycaprolactone Scaffolds With Angle-Ply Architecture For Annulus Fibrosus Tissue Engineering, Thomas R. Christiani, E Baroncini, Joseph F. Stanzione, Andrea J. Vernengo

Henry M. Rowan College of Engineering Departmental Research

Tissue engineering of the annulus fibrosus (AF) is currently being investigated as a treatment for intervertebral disc degeneration, a condition frequently associated with low back pain. The objective of this work was to use 3D printing to generate a novel scaffold for AF repair that mimics the structural and biomechanical properties of the native tissue. Multi-layer scaffolds were fabricated by depositing polycaprolactone struts in opposing angular orientations, replicating the angle-ply arrangement of the native AF tissue. Scaffolds were printed with varied strut diameter and spacing. The constructs were characterized morphologically and by static and dynamic mechanical analyses. Scaffold surfaces were …

Fabrication Of Enhanced Carbon Based Biocompatible And Biodegradable Microelectronic Materials Derived From Lignocellulosic Biomass, Harrison Thomas Hawkins

Theses and Dissertations

The development of materials capable of harmlessly being broken down and removed from the body is a crucial step towards the development of short-term application electronic biomedical implants. Once developed, these implants, known as bioresorbable electronics, will open a wide array of temporary applications in the field of biomedical implantable devices. Necessary to the operation of bioresorbable electronics within the body is a power source that is similarly biocompatible and biodegradable. To this end, enhanced carbon-based materials and a bio-ionic liquid were developed for the fabrication of a preliminary implantable and bioresorbable battery and tested for functional properties. Electrodes were …

Diagnosing Growth In Low-Grade Gliomas With And Without Longitudinal Volume Measurements: A Retrospective Observational Study., Hassan M Fathallah-Shaykh, Andrew Deatkine, Elizabeth Coffee, Elias Khayat, Asim K Bag, Xiaosi Han, Paula Province Warren, Markus Bredel, John Fiveash, James Markert, Nidhal Carla Bouaynaya, Louis B Nabors

Henry M. Rowan College of Engineering Departmental Research

BACKGROUND: Low-grade gliomas cause significant neurological morbidity by brain invasion. There is no universally accepted objective technique available for detection of enlargement of low-grade gliomas in the clinical setting; subjective evaluation by clinicians using visual comparison of longitudinal radiological studies is the gold standard. The aim of this study is to determine whether a computer-assisted diagnosis (CAD) method helps physicians detect earlier growth of low-grade gliomas.

METHODS AND FINDINGS: We reviewed 165 patients diagnosed with grade 2 gliomas, seen at the University of Alabama at Birmingham clinics from 1 July 2017 to 14 May 2018. MRI scans were collected during …

Harnessing Neurovascular Interaction To Guide Axon Growth., Paul P Partyka, Ying Jin, Julien Bouyer, Angelica Dasilva, George A Godsey, Robert G Nagele, Itzhak Fischer, Peter Galie

Henry M. Rowan College of Engineering Departmental Research

Regulating the intrinsic interactions between blood vessels and nerve cells has the potential to enhance repair and regeneration of the central nervous system. Here, we evaluate the efficacy of aligned microvessels to induce and control directional axon growth from neural progenitor cells in vitro and host axons in a rat spinal cord injury model. Interstitial fluid flow aligned microvessels generated from co-cultures of cerebral-derived endothelial cells and pericytes in a three-dimensional scaffold. The endothelial barrier function was evaluated by immunostaining for tight junction proteins and quantifying the permeability coefficient t (~10−7 cm/s). Addition of neural progenitor cells to the co-culture …

Inception Modules Enhance Brain Tumor Segmentation., Daniel E Cahall, Ghulam Rasool, Nidhal Carla Bouaynaya, Hassan M Fathallah-Shaykh

Henry M. Rowan College of Engineering Departmental Research

Magnetic resonance images of brain tumors are routinely used in neuro-oncology clinics for diagnosis, treatment planning, and post-treatment tumor surveillance. Currently, physicians spend considerable time manually delineating different structures of the brain. Spatial and structural variations, as well as intensity inhomogeneity across images, make the problem of computer-assisted segmentation very challenging. We propose a new image segmentation framework for tumor delineation that benefits from two state-of-the-art machine learning architectures in computer vision, i.e., Inception modules and U-Net image segmentation architecture. Furthermore, our framework includes two learning regimes, i.e., learning to segment intra-tumoral structures (necrotic and non-enhancing tumor core, peritumoral edema, …

Evaluating Nanoshells And A Potent Biladiene Photosensitizer For Dual Photothermal And Photodynamic Therapy Of Triple Negative Breast Cancer Cells., Rachel S. Riley, Rachel K O'Sullivan, Andrea M Potocny, Joel Rosenthal, Emily S Day

Henry M. Rowan College of Engineering Departmental Research

Light-activated therapies are ideal for treating cancer because they are non-invasive and highly specific to the area of light application. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two types of light-activated therapies that show great promise for treating solid tumors. In PTT, nanoparticles embedded within tumors emit heat in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT …

Efficacy Of Eluted Antibiotics In 3d Printed Orthopaedic Implants, Mohammed Mehdi Benmassaoud

Theses and Dissertations

Costs associated with musculoskeletal diseases in the United States account for 5.7 % of the Gross Domestic Product (GDP) [1]. As such, there is a need to pursue new ideas in orthopaedic implants that can decrease cost and improve patient care. In the recent years, 3D printing using Fused Deposition Modeling (FDM) or Stereolithography (SLA) has opened several exciting possibilities to create orthopaedic implants. Such implants can be engineered to release antibiotics in a controlled manner either by infusing the drug into the material during manufacturing or by using built-in design features such as micro-channels and reservoirs [2]. The use …

Kinematic Analysis Of Spinal Cord Injury Animals Treated With A Neurotrophin-Infused Scaffold And Body Weight Supported Treadmill Training, Alexander Herman

Theses and Dissertations

Spinal Cord Injury (SCI) is a condition that affects around 250,000 Americans with no cure. Existing treatments rely on physical therapies such as body weight support treadmill training (BWSTT). Treatments currently being researched include the use of implantable cells and biomaterials. Our study investigated the changes in locomotive gait and range of motion via a combinational treatment using a bioengineered scaffold [poly (N-isopropyl acrylamide) polyethylene glycol (PNIPAAm-g-PEG) with BDNF and NT-3] and rehabilitation training using BWSTT in a clinically relevant contusion SCI animal model. Five different groups of animals (Sham, Injury, BWSTT, Implant, and Combinational) were tested on a treadmill …

Thermal Fluid Models Of A Hydrogel Delivery System For Pancreatic Cancer Treatment, Nesrine Bouhrira

Theses and Dissertations

Pancreatic cancer is one of the most devastating cancers with low survival rates. This disease is difficult to detect due to the pancreas's location deep within the body. Therefore, diagnoses are often made in the later stages, making treatment options more limited and difficult. It has been hypothesized that direct injection into the tumor would enhance drug effectivenes. Therefore, we examined the use of endoscopic ultrasound (EUS) combined with a fine needle injection to deliver a drug-eluding thermosensitive hydrogel directly into the tumor. Unfortunately normal body temperatures surrounding the EUS can warm the hydrogel drug combination beyond its phase transition …

High Throughput Analysis Of The Penetration Of Iron Oxide/Polyethylene Glycol Nanoparticles Into Multicellular Breast Cancer Tumor Spheroids, Jonathan Robert Gabriel

Theses and Dissertations

The purpose of this study was to design and optimize a system for the high-throughput analysis of multicellular tumor spheroids (MCTS), and validate the system through the study of a complex biological model. The system was successfully created and optimized, allowing the histological recovery of MCTS at rates up to 90% for microarrays of 24-spheroids. Arrays of 96-spheroids were recovered at rates up to 86%. The system was used to study the penetration of 5k Da-polyethylene coated superparamagnetic iron-oxide nanoparticles (5k-PEG SPIONs) into HTB-126 breast cancer spheroids cultured to a mean diameter of 486 micrometer (± 25.2 micrometer). Results were …

Effects Of Passive And Active Training Paradigms On Bone And Muscle Recovery After Spinal Cord Injury, Brittany Lynn King

Theses and Dissertations

The effects spinal cord injury (SCI) has have been studied in both human and animal models. Specifically in incomplete SCI, the bone degradation and muscle atrophy seen in the lower limbs has been documented, along with the effects of different training paradigms on bone and muscle loss. This study implemented a clinically relevant animal model of a moderate spinal contusion injury at the T9--T10 level, along with active body weight supported treadmill training (BWSTT) and passive bike training, to compare the effects such training methods have on the bone microstructure properties and muscle masses in the lower limbs of rats. …

Effects Of Bioengineering Scaffolds Releasing Neurotrophins And Body Weight Supported Treadmill Training On H-Reflex After Spinal Cord Injury, Jaclyn Ann Witko

Theses and Dissertations

Changes in monosynaptic reflex, often used to study spasticity, has been tested through the H-reflex in spinal cord injury (SCI) patients after rehabilitation training, such as body weight support treadmill training or cycling. The combinational effects of rehabilitation training and a bioengineered scaffold on spasticity in SCI animal model have not been studied. We used a clinically relevant animal model of spinal cord moderate contusion at T9/T10 with BWSTT and the bioengineered scaffold PNIPAAm-g-PEG loaded with the growth factors BDNF/NT-3 to measure the efficiency of the combinational bioengineered approach to treat spasticity. Five animal groups were included in the study: …

Automatic Analysis Of Surface Electromyography Of Reflexes For Central Nervous System Inhibition During Pregnancy, Neda Parvin

Theses and Dissertations

Eclampsia is a life-threatening neurological complication (seizures or coma) of pregnancy, and represents progression of pre-eclampsia (high blood pressure and protein in the urine isolated to pregnancy). Even though the exact mechanism of pre-eclampsia and its neurological manifestations have yet to be definitively established, it is known that there is a loss of inhibitory impulses between the cerebral cortex and the spinal cord resulting in exaggerated reflexes. In this work, we establish normative measures for deep tendon reflexes (DTR) during pregnancy. We quantified the surface electromyogram (EMG) at the knee and ankle of DTRs in 279 subjects. The signals were …

Antibody-Nanoparticle Conjugates To Enhance The Sensitivity Of Elisa-Based Detection Methods., Margaret M Billingsley, Rachel S. Riley, Emily S Day

Henry M. Rowan College of Engineering Departmental Research

Accurate antigen detection is imperative for clinicians to diagnose disease, assess treatment success, and predict patient prognosis. The most common technique used for the detection of disease-associated biomarkers is the enzyme linked immunosorbent assay (ELISA). In an ELISA, primary antibodies are incubated with biological samples containing the biomarker of interest. Then, detectible secondary antibodies conjugated with horseradish peroxidase (HRP) bind the primary antibodies. Upon addition of a color-changing substrate, the samples provide a colorimetric signal that directly correlates to the targeted biomarker concentration. While ELISAs are effective for analyzing samples with high biomarker content, they lack the sensitivity required to …

Tumor Vessel Normalization After Aerobic Exercise Enhances Chemotherapeutic Efficacy., Keri L Schadler, Nicholas J Thomas, Peter Galie, Dong Ha Bhang, Kerry C Roby, Prince Addai, Jacob E Till, Kathleen Sturgeon, Alexander Zaslavsky, Christopher S Chen, Sandra Ryeom

Henry M. Rowan College of Engineering Departmental Research

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical …

Uncoupling Shear And Uniaxial Elastic Moduli Of Semiflexible Biopolymer Networks: Compression-Softening And Stretch-Stiffening., Anne S G Van Oosten, Mahsa Vahabi, Albert J Licup, Abhinav Sharma, Peter Galie, Fred C Mackintosh, Paul A Janmey

Henry M. Rowan College of Engineering Departmental Research

Gels formed by semiflexible filaments such as most biopolymers exhibit non-linear behavior in their response to shear deformation, e.g., with a pronounced strain stiffening and negative normal stress. These negative normal stresses suggest that networks would collapse axially when subject to shear stress. This coupling of axial and shear deformations can have particularly important consequences for extracellular matrices and collagenous tissues. Although measurements of uniaxial moduli have been made on biopolymer gels, these have not directly been related to the shear response. Here, we report measurements and simulations of axial and shear stresses exerted by a range of hydrogels subjected …