PhD, University of Cincinnati, 2018, Engineering and Applied Science: Biomedical Engineering

Myelomeningocele (MMC) is a neurologic defect characterized by failure of neural tube closure in the spinal column. This leads to cerebrospinal fluid leakage or contact with amniotic fluid, which can translate into sexual dysfunctions and paralysis after birth. The recently developed minimally-invasive technique for MMC repair is called fetoscopy, which involves a surgical patch, expanded for defect coverage on the fetus' back. Currently used inert patches do not degrade after implantation, necessitating a post-natal removal surgery, while collagen-based patches employed in are associated with poor mechanical integrity. Also, these patches are not tailored for fetoscopic MMC repair, and their response in fetal environment is unexplored. Deployment and expansion of coiled patch using surgical tools at defect site is time-consuming and cumbersome. Some of these existing patches have mesh-like structure for tissue in-growth, which makes their barrier properties debatable. Upon implantation at defect site, the patch encounters amniotic fluid and body fluids, as well as fluid forces due to fetal movement in the womb. This necessitates analysis of biodegradability and mechanical response of the patch for its adaptability in fetoscopic MMC repair. Taking the above requirements into consideration, we designed a patch comprising a blend of poly (L-lactic acid) (PLA) and poly (ε-caprolactone) (PCL), both polymers approved by the U.S. Food and Drug Administration for hard and soft tissue repair in spine. Different PLA-PCL formulations were characterized for surface and thermal properties, and the ideal formulation was chosen as our designed patch based on aptitude for thermal expansion at in-vivo temperature (37°C). This will enable self-expansion of the coiled patch at defect site, saving time and reducing difficulty level of surgery. The designed patch was characterized for barrier properties to ensure its watertight nature, and for biocompatibility after exposure to huma (open full item for complete abstract)

Committee: Chia-Ying Lin Ph.D. (Committee Chair); Yoonjee Park Ph.D. (Committee Member); Jose Peiro (Committee Member); Marepalli Rao Ph.D. (Committee Member) Subjects: Biomedical Research

MS, University of Cincinnati, 2016, Engineering and Applied Science: Materials Science

In this study, the effects of Ultrasonic Nanocrystal Surface Modification (UNSM) on residual stress, near surface microstructure, hardness, high cycle fatigue, biocompatibility and corrosion behaviour of a low-modulus beta Ti-35Nb-7Zr-5Ta-0.3O (wt %) was studied. The UNSM is novel mechanical surface treatment which effectively improves mechanical properties, fatigue life and wear of engineering components. UNSM causes severe plastic deformation on the surface, thus inducing deep compressive stresses and a surface nano-crystalline layer in the component which improves hardness, yield strength and fatigue life. At first, the as-received specimens were solution treated at 850º C for 1 hour and water quenched to obtain a single phase ß structure. The solution treated specimens were then subjected to UNSM treatment with two different static (20N and 50N) and dynamic loads (20% and 50%). The microstructure after UNSM was characterized by optical, scanning electron microscope (SEM), Electron Backscattered Diffraction (EBSD) and transmission electron Microscopy (TEM). Nanoindentation test was also performed to determine local properties like hardness with distance from the treated surface. The UNSM treated specimen induces compressive residual stresses as high as -1600 MPa and shows significant increase in surface hardness from 4.5 GPa to 6 GPa. The residual compressive stresses and hardness increases with increase in static load. The severe plastic deformation caused by UNSM produces nanocrystalline layer of about 1 µm from the treated surface and a gradient microstructure of deformation bands and high dislocation density which was confirmed by transmission electron microscopy. The deformation mechanism after UNSM was also studied. The deformation mechanism in this alloy is dominated by dislocation movement and occurrence of deformation bands with high dislocation density. Three-point bending fatigue tests were also performed to study improvement in fatigue life (open full item for complete abstract)

Committee: Vijay Vasudevan Ph.D. (Committee Chair); Ashley Paz y Puente Ph.D. (Committee Member); Rodney Roseman Ph.D. (Committee Member) Subjects: Materials Science

Master of Sciences (Engineering), Case Western Reserve University, 2016, Biomedical Engineering

Woven collagen meshes crosslinked using either genipin or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS), as well as synthetic and xenograft materials used for the management of stress urinary incontinence, were implanted in a subcutaneous rat model to evaluate biocompatibility and changes in mechanical properties over time. The performance of materials were compared to determine if woven collagen meshes could be used for management of stress urinary incontinence. Both woven collagen meshes elicited a more facile chronic inflammatory response than synthetic or xenograft materials. However, genipin crosslinked collagen meshes initiated patent tissue ingrowth while EDC/NHS crosslinked collagen meshes did not. Because of this, the mechanical properties of genipin crosslinked collagen meshes most closely matched those of native tissues over time. Overall, the host response and mechanical properties of genipin crosslinked collagen meshes in this subcutaneous animal model show promise for their potential as a new material for management of stress urinary incontinence.

Committee: Ozan Akkus PhD (Advisor); Jeffrey Capadona PhD (Committee Member); Steven Eppell PhD (Committee Member) Subjects: Biomedical Engineering; Biomedical Research

PhD, University of Cincinnati, 2012, Engineering and Applied Science: Materials Science

Magnesium (Mg) and its alloys are emerging as a possible biodegradable implant material. The corrosion behavior of pure Mg, AZ31, and AZ91D were evaluated in various In Vitro and In Vivo environments to investigate their potential application of being biomaterials. Mg implants may degrade too quickly in the body, before the natural healing process is complete. Anodization is known to be an effective approach for slowing down the initial corrosion rate of magnesium (Mg) and its alloys. Anodization was investigated to slow down the initial corrosion of Mg in a simulated body corrosive environment. Pure Mg and AZ91D alloy were anodized and their corrosion resistance was compared in terms of anodization behavior and parameters such as applied voltage and current with different anodization time. Electrochemical impedance spectroscopy, DC polarization, and immersion testing were used to evaluate the corrosion resistance of Mg samples and further optimize anodization parameters. The results showed that anodization increased the corrosion resistance of both pure Mg and AZ91D samples. Further characterization showed the anodized layers on both pure Mg and AZ91D consisted of Mg, O and Si, in the mixture of MgO and Mg2SiO4. The anodization of AZ91D was further investigated by studying the specific use of oxy-salts to improve the corrosion resistance of anodization coatings. Oxy-salts of silicate, phosphate, and carbonate were added separately to a sodium hydroxide alkaline electrolyte used for anodization. This modified process was investigated in terms of anodizing behavior, the surface properties of the film, and enhanced corrosion protection of the metal. Anodization of AZ91D using the silicate containing electrolyte generated sparks and increased the electrolyte temperature, and produced a thicker and more corrosion resistant layer than the other oxy-salts. In this process, MgO and SiO2 formed Mg2SiO4 at high temperature and silicon (Si) in the anodized coating was mainly (open full item for complete abstract)

Committee: Vesselin Shanov PhD (Committee Chair); YeoHeung Yun PhD (Committee Member); Stephen Clarson PhD (Committee Member); Mark Schulz PhD (Committee Member) Subjects: Metallurgy

Doctor of Philosophy, The Ohio State University, 2004, Dentistry

Palladium-based alloys have been used as dental restorative materials for about two decades with good clinical history. But there have been clinical case reports showing possible allergy effects from these alloys. The aim of this study was to characterize the corrosion behavior and mechanisms of several palladium-based dental alloys by potentiodynamic polarization methods, electrochemical impedance spectroscopy (EIS), and scanning Kelvin probe force microscopy/atomic force microscopy (SKPFM/AFM), and to evaluate their biocompatibility by a cell culture technique and an animal model. Using SKPFM/AFM and scanning electron microscopy, the Ru enriched phase from the use of ruthenium as a grain-refining element was identified as being slightly more noble than the palladium solid solution matrix in a high-palladium alloy. Other secondary precipitates that exist in the microstructures of these high-palladium alloys have minimal differences in Volta potential compared to the matrix. For high-palladium alloys, corrosion is generally uniform due to the predominant palladium content in the different phases. Potentiodynamic polarization and EIS have shown that representative palladium-silver alloys have low corrosion tendency and high corrosion resistance, which are equivalent to a well-known high-noble gold-palladium alloy in simulated body fluid and oral environments. The palladium-silver alloys tested are resistant to chloride ion corrosion. Passivation and dealloying have been identified for all of the tested palladium-silver alloys. The great similarity in corrosion behavior among the palladium-silver alloys is attributed to their similar chemical compositions. The variation in microstructures of palladium-silver alloys tested does not cause significant difference in corrosion behavior. The corrosion resistance of these palladium-silver alloys at elevated potentials relevant to oral environment is still satisfactory. The release of elements from representative dental palla (open full item for complete abstract)

Committee: William Brantley (Advisor) Subjects:

Doctor of Philosophy, Case Western Reserve University, 2011, Biomedical Engineering

Rotator cuff tendon injury is a debilitating health concern that affects more than 40% of the aging population. Despite advances in surgical treatment, the failure rate of rotator cuff repairs ranges 20-90%. Naturally-occurring extracellular matrices (ECMs) have been recently investigated as augmentation scaffolds, but none has yet demonstrated both the appropriate biological and mechanical properties. This dissertation proposes to enrich fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) for rotator cuff repair. The central hypothesis is that TS-HA treatment will decrease chronic inflammation without decreasing the time-zero or post-implantation mechanical properties of fascia. The specific aims are to develop a TS-HA treatment method and to evaluate the host response and concomitant mechanical properties of treated fascia in a rat abdominal wall model. TS-HA treatment increased the HA content of fascia by an order of magnitude to ~1% tissue weight. The incorporated HA was distributed throughout the ECM and, upon cross-linking, was retained as a hydrogel network. Cross-linked TS-HA treated fascia exhibited an increased macrophage and giant cell response and a lower density of fibroblast-like cells than water treated controls. Treated fascia, with or without cross-linking, exhibited a predominantly M2 pro-remodeling macrophage profile similar to water controls, which is suggestive of constructive tissue remodeling. All grafts exhibited a chronic lymphocytic response that is suggestive of an immune response to the fascia xenograft. Fascia samples in all groups demonstrated time-dependent decreases in mechanical properties. Cross-linked TS-HA treated fascia exhibited a lower toe-region elastic modulus and trended towards a higher transition strain than water treated controls not only after implantation, but also at time zero. These findings demonstrate that HA augmentation can alter both the host response and the mechanical properties of f (open full item for complete abstract)

Committee: Kathleen Derwin PhD (Advisor); Roger Marchant PhD (Committee Chair); Eben Alsberg PhD (Committee Member); Thomas Bauer MD, PhD (Committee Member); Vince Hascall PhD (Committee Member) Subjects: Biomedical Engineering

Doctor of Philosophy, University of Akron, 2010, Polymer Engineering

The prolonged contact of blood with the synthetic polymeric surface in hemodialysis leads to two very important long term complications viz., dialysis induced oxidative stress (DIOS), and membrane induced inflammation (MII). Therefore an attempt was made in this dissertation to fabricate hemodialysis membranes that were modified with phytochemicals, which could potentially reduce both DIOS and MII. Phytochemicals are non-nutritive plant-derived chemicals that are reported to have multiple disease preventing properties. Mangiferin, a phytochemical derived from mango tree and genistein, which is a soy-bean derived phytochemical were chosen based on superior anti-oxidant and anti-inflammatory properties. Membranes were decided to be modified by solution blending of phytochemicals with the polymer solution (physical modification) used to fabricate the membranes. Miscibility characteristics of poly(amide)/poly(vinyl pyrrolidone)/mangiferin and poly(ether sulfone)/poly(vinyl pyrrolidone)/mangiferin blends were established. Membranes were cast in form of film via non-solvent induced phase separation process. Here DMSO was employed as solvent and water was employed as non-solvent. Unmodified membranes typically showed a dense skin layer while the cross section showed finger-like channel which progressively increased in diameter along the thickness. This gradient morphology ensures sufficient pressure gradient for the toxins to be removed from the blood to the dialysate stream. Mangiferin modification of PA membranes led to an increase in surface porosity of the membranes whereas PA/PVP/mangiferin membranes not only showed microporous surface but also network structure. Membrane modification was also performed with genistein. Even at very low genistein concentration embedded crystals were observed on the membrane surface. As the concentration of genistein increased large spherulitic structures evolved on the membrane surface. The anti-oxidant properties of pure phytoch (open full item for complete abstract)

Committee: Thein Kyu Dr. (Advisor) Subjects: Agricultural Chemicals; Biomedical Research; Engineering; Health Care; Immunology; Materials Science; Polymers

Doctor of Philosophy, University of Akron, 2009, Chemical Engineering

L-tyrosine based ‘pseudo' poly (amino acids) such as polyphosphates and polyurethanes have been developed using desaminotyrosine tyrosyl hexyl ester (DTH) as the monomer, and characterized with the aim of using them for biomedical applications. The successful establishment of the biocompatibility of these novel materials is critical for their success and acceptance in the biomedical device field. One of the main aims of the research presented in this dissertation has been to evaluate the biocompatibility of novel L-tyrosine based polymers and their degradation products by examining their cytotoxicity, investigating the adhesion and proliferation of human fibroblast cells on L-tyrosine based polymeric substrates, and correlating the cell adhesion to surface wettability and composition of the substrates. Characterization results of L-tyrosine based polyurethanes and polyphosphate have shown that although these polymers are synthesized using a common monomer, they exhibit dramatically different physico-mechanical properties. Another aim of this dissertation has been to examine the blending of polyphosphate and polyurethanes in order to develop materials with a wider spectrum of physico-mechanical properties and thus obtain a stepwise transition in the material properties by adjusting the blends composition. The blends have been extensively characterized for different bioengineering properties including surface and bulk characteristics. In addition, the possibility of application of polyphosphate and polyurethanes for the formulation of controlled drug delivery devices has been investigated. Drug delivery devices in the form of microparticles and electrospun micro- and nano-fibrous membranes have been developed and certain process parameters associated with the formulation process have been optimized. The results indicate that L-tyrosine based polymers and their degradation products are non-cytotoxic under test conditions (dosages and time frames examined). The adhe (open full item for complete abstract)

Committee: Stephanie Lopina PhD, PE (Advisor); Yang Yun PhD (Advisor) Subjects: Biomedical Research; Chemical Engineering; Polymers

Doctor of Philosophy, University of Akron, 2005, Chemical Engineering

The long-term clinical success of autologous vein and synthetic vascular grafts is limited due to the development of anastomotic intimal hyperplasia (IH). Previously published data suggests that cyclosporine (CyA) (an immunosuppressive drug) may reduce the development of IH in a canine model [1]. However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporine from a polymeric vascular wrap will prevent the development of IH. In order to test this hypothesis, we developed three controlled release polymeric devices that could be placed around vascular graft anastomotic sites to deliver therapeutic drugs locally. The first device is a poly(ethylene glycol) (PEG) hydrogel sheet. The second device is a composite device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres dispersed in the PEG hydrogel sheet. The third device is in the form of a ring (referred to as PolyRing from here on) that can be slipped around the anastomotic sites. PolyRing is a composite polymeric device consisting of PLGA microspheres embedded in a PEG hydrogel. In-vitro studies were conducted on the three devices to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice. In-vivo studies were conducted on a swine model to evaluate the biocompatibility, drug optimization and efficacy of PolyRing. The biocompatibility study utilized four (4) domestic swine with non-drug loaded PolyRings harvested at two (2) and four (4) week time points. PolyRings (ID 3-5 mm; OD 7-8 mm; Length 5 mm) were implanted in subcutaneous and muscular tissues and around jugular veins and carotid arteries. The histological findings of gamma sterilized PolyRing implants at two and four weeks demonstrated the biocompatibility of this device. A minimal foreign body reacti (open full item for complete abstract)

Committee: Stephanie Lopina (Advisor) Subjects: