Fischell Department of Bioengineering Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/6628
Browse
17 results
Search Results
Item CHARACTERIZATION OF FOCUSED ULTRASOUND BEAM GEOMETRIES USING THERMOCHROMIC LIQUID CRYSTAL FILMS(2020) Ahmed, Nabid; Zhang, Li-Qun; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Focused ultrasound (FUS) applications are gaining more attention from clinicians for being able to provide effective, non-invasive treatments to almost any region of the body. In-house development of FUS devices require characterization and quality assurance methods to verify acoustic pressure fields, focal zone geometry, location, and validate proper function. Conventional techniques (hydrophones, gel phantoms) are limited by expensive and inaccessible equipment, time-consuming procedures, and use of toxic reagents. We developed a process for using thermochromic liquid crystal (TLC) films, sensors which undergo color transition when exposed to a range of specific temperatures, as a low-cost and readily adaptable characterization method for FUS transducers. A proof-of-concept experiment showed reproducibility in detecting ultrasound beams. Tests with two FUS transducers demonstrated that the technique was able to approximate axial dimensions of the focal region and depth of the focal region, characteristics that are significant in FUS treatment planning.Item Dual-Chambered Membrane Bioreactor for the Dynamic Co-Culture of Dermal Stratified Tissues(2019) Navarro Rueda, Javier; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Every year over 11 million patients suffer severe burns worldwide. Facial burn statistics include victims of violence (warfare, acid attacks, scalding) and trauma (flame, electrical, chemical). Skin is the first barrier against external mechanical and biochemical factors, such as burning agents, and is composed of the epidermis, dermis, and hypodermis layers. When burned, skin cannot regulate temperature or fluid transport, or stop bacterial infection. Due to the importance of the skin barrier, natural healing and grafting treatments aim to quickly close the wounds with fast proliferation of fibroblasts and collagen deposition, a process that results in scarring, loss of function, and disfigurement. Tissue engineering has produced epidermis-dermis skin scaffolds for clinical use and in vitro dermal models. Throughout this work we studied 3D printing and bioreactor strategies for the simultaneous physiologic and topographic reconstruction of burnt facial skin tissues. First, we formulated a keratin-based bioink that can be used for 3D printing on a lithography-based 3D printer. Second, we implemented the keratin bioink in the production of Halofuginone-laden face masks for the improvement of contracture, scarring, and aesthetics in severe skin wound healing in an animal model. Due to lack of collagen organization and microstructural development, we introduced a novel dual-chambered (DCB) bioreactor system to study stratified tissues. For this, crosslinking density of the keratin-based hydrogels was used to fine tune the transport properties of membranes for potential use in guided tissue regeneration applications. Then, we assessed the viability of our novel DCB for co-culturing adjacent cell populations with the inclusion of a regulatory keratin membrane. Last, having studied the DCB with flat interfaces, we assessed its viability for perfusing curved interfaces. The integration of both curvature and cell populations allowed to assess the synergistic development of adjacent dermis fibroblasts and hypodermis stem-cell-derived adipocytes and evaluate whether including topography parameters would alter cell viability in the DCB. The strategies developed here elucidate on tissue stratification and aesthetic reconstruction. Furthermore, the keratin-based bioink, the engineered membranes, and the DCBs can be extended to study other stratified or gradient tissues and to fine-tune communication between cell populations in complex 3D constructs.Item FAILURE MECHANISMS OF PEDIATRIC GROWING ROD CONSTRUCTS(2017) Hill, Genevieve A-L.; Fisher, John P; Dreher, Maureen L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Early onset scoliosis (EOS) affects a vulnerable population of young children, and occurs at critical ages when the spine and thorax are developing. Children suffering with EOS have higher mortality rates due to cardiopulmonary complications; therefore, treatment for these patients can be life-saving. Pediatric growing rod constructs are an important treatment option for young patients with severe and progressive spinal deformities because they encourage growth and correction of the spinal curvature through successive lengthening procedures. However, growing rod constructs suffer from complication rates as high as 72%, which often lead to unplanned reoperations. To help prevent future failures of the same root cause, the failure mode and mechanism must be identified, which tell us how and why the devices failed respectively. This research included the first study to examine multiple, retrieved pediatric growing rod constructs from various sites to systematically investigate these significant items. The retrieval study revealed that rod fracture (failure mode) was due to bending fatigue (failure mechanism), and stress concentrations play an important role in rod fractures. The information obtained from the retrieval study enhanced the understanding of in vivo loading conditions experienced by the device and established clinically-relevant parameters for a mechanical bench model. This research also included the development and validation of a novel mechanical bench model that successfully replicated rod fracture due to bending fatigue. A mechanical bench model that is predicated on clinical outcomes can serve as a tool for engineers and researchers who are looking to improve pediatric growing rod constructs as it will enable them to make relevant predictions about the device’s resistance to failure. For example, the model was used in this research to investigate how the unique characteristics of pediatric growing rod constructs such as construct configuration and lengthening affect mechanical performance of the device. Key recommendations regarding surgical technique were identified in the retrieval study and verified through bench testing. The data obtained during this research can ultimately be used to reduce failure rates and unplanned revisions in this patient population.Item NOVEL TECHNOLOGIES AND APPLICATIONS FOR FLUORESCENT LAMINAR OPTICAL TOMOGRAPHY(2017) Tang, Qinggong Tang; Chen, Yu; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Laminar optical tomography (LOT) is a mesoscopic three-dimensional (3D) optical imaging technique that can achieve both a resolution of 100-200 µm and a penetration depth of 2-3 mm based either on absorption or fluorescence contrast. Fluorescence laminar optical tomography (FLOT) can also provide large field-of-view (FOV) and high acquisition speed. All of these advantages make FLOT suitable for 3D depth-resolved imaging in tissue engineering, neuroscience, and oncology. In this study, by incorporating the high-dynamic-range (HDR) method widely used in digital cameras, we presented the HDR-FLOT. HDR-FLOT can moderate the limited dynamic range of the charge-coupled device-based system in FLOT and thus increase penetration depth and improve the ability to image fluorescent samples with a large concentration difference. For functional mapping of brain activities, we applied FLOT to record 3D neural activities evoked in the whisker system of mice by deflection of a single whisker in vivo. We utilized FLOT to investigate the cell viability, migration, and bone mineralization within bone tissue engineering scaffolds in situ, which allows depth-resolved molecular characterization of engineered tissues in 3D. Moreover, we investigated the feasibility of the multi-modal optical imaging approach including high-resolution optical coherence tomography (OCT) and high-sensitivity FLOT for structural and molecular imaging of colon tumors, which has demonstrated more accurate diagnosis with 88.23% (82.35%) for sensitivity (specificity) compared to either modality alone. We further applied the multi-modal imaging system to monitor the drug distribution and therapeutic effects during and after Photo-immunotherapy (PIT) in situ and in vivo, which is a novel low-side-effect targeted cancer therapy. A minimally-invasive two-channel fluorescence fiber bundle imaging system and a two-photon microscopy system combined with a micro-prism were also developed to verify the results.Item Harnessing Degradable Materials to Study and Engineer Lymph Node Function(2017) Andorko, James; Jewell, Christopher M; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Vaccines have benefited global health by controlling or eradicating multiple previously fatal diseases. While many early vaccines were efficacious, sophisticated new vaccines and immunotherapies need to address current challenges in the field, including diseases that avoid immune detection or lack strong molecular targets for the immune system. Overcoming these hurdles requires strategies to specifically control the magnitude and type of immune response generated. Biomaterials offer attractive features to achieve this goal, including protection of encapsulated signals, controlled release of cargos, and tunable features for cell targeting. Intriguingly, recent research reveals many common biomaterials activate the immune system, even without other signals. This intrinsic activation results, at least in part, from biomaterial physicochemical features that mimic pathogens and other foreign materials. Surprisingly, although degradable materials are being intensely studied as vaccines carriers, little research has investigated how the intrinsic immunogenicity of these materials changes as polymers degrade. The work in this dissertation reveals parameters impacting material intrinsic immunogenicity and exploits this new understanding to test the influence of biomaterial-based vaccines on the function of lymph nodes (LNs), key tissues that coordinate immunity. In the first aim, the immunostimulatory properties of a library of degradable polymers, poly(beta-amino esters) (PBAEs), were investigated in cell and animal models. PBAEs in soluble forms did not activate innate immune cells (e.g., dendritic cells, DCs). When PBAEs were formulated into particles to mimic a common vaccine strategy, DC activation increased in a molecular weight-specific manner. Using intra-lymph node (i.LN.) injection, a novel technique to control the dose, kinetics, and combination of signals in LNs, PBAE intrinsic immunogenicity was confirmed in mice. In the second aim, microparticles encapsulating immune signals were introduced into mice via i.LN. injection and immune responses were quantified in treated LNs, untreated LNs, and in blood. These results elucidated the interplay between local LN rearrangement and systemic antigen-specific responses which ultimately led to prolonged survival in cancer models. By understanding how the properties and administration of biomaterial-based vaccines impact immunity, this dissertation provides information that can help create new design rules for future vaccines that actively direct the immune system toward a desired response.Item Feasibility of in vivo SAXS imaging for detection of Alzheimer's disease(2017) Choi, Mina; Chen, Yu; Badano, Aldo; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Small-angle x-ray scattering (SAXS) imaging has been proposed as a technique to characterize and selectively image structures based on electron density structure which allows for discriminating materials based on their scatter cross sections. This dissertation explores the feasibility of SAXS imaging for the detection of Alzheimer's disease (AD) amyloid plaques. The inherent scatter cross sections of amyloid plaque serve as biomarkers in vivo without the need of injected molecular tags. SAXS imaging can also assist in a better understanding of how these biomarkers play a role in Alzheimer’s disease which in turn can lead to the development of more effective disease-modifying therapies. I implement simulations of x-ray transport using Monte Carlo methods for SAXS imaging enabling accurate calculation of radiation dose and image quality in SAXS-computed tomography (CT). I describe SAXS imaging phantoms with tissue-mimicking material and embedded scatter targets as a way of demonstrating the characteristics of SAXS imaging. I also performed a comprehensive study of scattering cross sections of brain tissue from measurements of ex-vivo sections of a wild-type mouse brain and reported generalized cross sections of gray matter, white matter, and corpus callosum obtained and registered by planar SAXS imaging. Finally, I demonstrate the ability of SAXS imaging to locate an amyloid fibril pellet within a brain section. This work contributes to novel application of SAXS imaging for Alzheimer's disease detection and studies its feasibility as an imaging tool for AD biomarkers.Item TOWARDS AN UNDERSTANDING OF THE DEGRADATION MECHANISMS OF UHMWPE-BASED SOFT BALLISTIC INSERTS(2016) TSINAS, ZOIS; Al-Sheikhly, Mohamad; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The objective of this work is to advance the field of lightweight and soft ultra-high molecular weight polyethylene (UHMWPE) inserts used in ballistic resistant-body armor, through the evaluation of chemical and physical degradation, and provide critical insight into the mechanisms involved. These inserts are comprised of non-woven UHMWPE fibers, foil-matrix low density polyethylene (LDPE), and a binder resin. Degradation of these components can be initiated by mechanical stress induced by routine use of the armor, thermal exposure due to storage and wear, and exposure to humidity and oxygen. Degradation of this system may include C-C and C-H bond ruptures resulting in C-centered radicals, thermo-oxidative reactions, as well as changes in the degree of crystallinity and the crystalline morphology of the UHMWPE fibers. This is the first comprehensive study on degraded UHMWPE-fibers extracted from body armor that have been subjected to accelerated aging. Previous studies have only focused on oxygen uptake and changes in the tensile strength of virgin UHMWPE fibers as markers of degradation. This work extends beyond oxygen uptake, to examine changes in the topography, the degree of crystallinity, and the crystal phases of UHMWPE fibers. Mechanical stress was found to be the main cause of kink band formation in UHMWPE fibers. Additionally, oxidation products and molecular oxygen were found to be at higher concentrations in the kink bands compared to other parts of the fiber. This suggests a synergistic effect between mechanical stress induced kink bands and oxidative degradation. The degree of crystallinity of the fibers did not change significantly, however morphological changes of the crystalline phases and changes in the orientation of the crystals were observed. Finally, this study investigates, for the first time, the degradation of the binder material that retains the fibers together in the laminates. The binder resin used in the laminates was identified to be a copolymer of polystyrene and polyisoprene, which undergoes oxidative degradation accompanied by a decrease in the weight-average molecular weight.Item Dual Quorum Quenching Capsules: Disrupting two bacterial communication pathways that lead to virulence(2016) Rhoads, Melissa Katherine; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Healthcare Associated Infections (HAIs) in the United States, are estimated to cost nearly $10 billion annually. And, while device-related infections have decreased, the 60% attributed to pneumonia, gastrointestinal pathogens and surgical site infections (SSIs) remain prevalent. Furthermore, these are often complicated by antibacterial resistance that ultimately cause 2 million illnesses and 23,000 deaths in the US annually. Antibacterial resistance is an issue increasing in severity as existing antibiotics are losing effectiveness, and fewer new antibiotics are being developed. As a result, new methods of combating bacterial virulence are required. Modulating communications of bacteria can alter phenotype, such as biofilm formation and toxin production. Disrupting these communications provides a means of controlling virulence without directly interacting with the bacteria of interest, a strategy contrary to traditional antibiotics. Inter- and intra-species bacterial communication is commonly called quorum sensing because the communication molecules have been linked to phenotypic changes based on bacterial population dynamics. By disrupting the communication, a method called ‘quorum quenching’, bacterial phenotype can be altered. Virulence of bacteria is both population and species dependent; each species will secrete different toxic molecules, and total population will affect bacterial phenotype9. Here, the kinase LsrK and lactonase SsoPox were combined to simultaneously disrupt two different communication pathways with direct ties to virulence leading to SSIs, gastrointestinal infection and pneumonia. To deliver these enzymes for site-specific virulence prevention, two naturally occurring polymers were used, chitosan and alginate. Chitosan, from crustacean shells, and alginate, from seaweed, are frequently studied due to their biocompatibility, availability, self-assembly and biodegrading properties and have already been verified in vivo for wound-dressing. In this work, a novel functionalized capsule of quorum quenching enzymes and biocompatible polymers was constructed and demonstrated to have dual-quenching capability. This combination of immobilized enzymes has the potential for preventing biofilm formation and reducing bacterial toxicity in a wide variety of medical and non-medical applications.Item Thermoplastic microfluidic technologies for portable and disposable bioanalytical and diagnostic platforms(2015) Rahmanian, Omid David; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Portable and cost-effective medical diagnostic technologies that require minimal external infrastructure for their operation are highly desirable for on-field military operations, defense against acts of bioterrorism, and infectious disease screening in resource-limited environments. Miniaturized Total Analysis Systems (µTAS) have the potential to fulfill this un-met need via low-cost, portable, and disposable point-of-care (POC) diagnostic devices. Inherent advantages of µTAS systems can be utilized to transform diagnostic technologies that currently require significant investment in centralized laboratories and highly trained personnel into automated, integrated, and miniaturized platforms. This dissertation addresses the development of microfabrication techniques and resulting component technologies that are realized in low-cost thermoplastic substrates. A thermoplastic microfabrication technique termed orogenic microfabrication, based on a non-reversible solvent-assisted swelling mechanism, is developed to provide unique capabilities for microscale and nanoscale patterning in rigid thermoplastics with minimal infrastructure. Orogenic microfabrication is compatible with multiple masking techniques including photolithography, chemical surface modification, contact and noncontact spotting, and inkjet deposition techniques, with each masking method offering unique influence on resulting orogenic structures that can be applied to microfluidic and µTAS systems. Direct ink masking is further explored as a low-cost rapid prototyping tool for fabrication of simple microfluidic devices where channel formation and bonding are combined into a single step, resulting in fully enclosed microfluidic channels within 30 minutes. Chemical surface passivation by UV-ozone treatment is utilized in combination with orogenic swelling and thermocompression bonding to develop single-use burst valves with tunable burst pressures. In addition to assisting in on-chip fluid manipulation, the normally closed burst valves enable on-chip reagent packaging and hermetic sealing of bioactive material in lyophilized format, and can be used for delivery of stored reagents for a range of disposable point-of-care assays. On-chip integrated micropumps are also developed, using simple fabrication process compatible with conventional thermoplastic fabrication techniques such as direct micromilling or injection molding. Direct displacement of liquid reagents using screw-assisted pumping can be operated either automatically or manually, with on-demand delivery of liquid reagents in a wide range of flow rates typically used in microfluidic applications. Collectively, the technologies developed in this dissertation may be applied to the future development of simple, disposable, and portable diagnostic devices that have the potential to be operated without off-chip instrumentation. On-chip storage of buffers and reagents in either dry or liquid format, and on-demand delivery of liquid reagents is packaged in a miniaturized, portable, and automated platform that can be operated in resource-constrained settings by practitioners with minimal expertise.Item Interference Studies Using Multidimensional Mapping of Cross-Reactive Sensors: Applications in Blood Monitoring of Clozapine(2014) Chocron, Sheryl E.; Ghodssi, Reza; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Point-of-care sensors are used in clinical applications for diagnosing and monitoring health conditions. For example, a point-of-care sensor for therapeutic drug monitoring of the clozapine antipsychotic can reduce burdens from guidelines suggesting routine monitoring of this medication. However, when measuring chemical markers in complex fluids, there are challenges related to decreased sensor performance due to chemical interference. This work presents a methodology for identifying individual interfering species. A set of cross-reactive electrochemical sensors were developed, whose diversified responses provide a fingerprint-type pattern capable of differentiating various species. By mapping the multidimensional responses, patterns from complex solutions were discerned and matched to those of individual species. Applying this methodology to clozapine sensing in blood, a major source of chemical interference was identified. The understanding matrix components that cause interference can guide the design of reliable sensing systems and can be integrated with pattern recognition tools that can account for it.