A Physical And Computational Reverse-Engineering Approach To Determine Dimensional Change And Its Relationship To Oxidation In Retrieved Orthopedic Implants, Josephine Kalshoven

ENGS 88 Honors Thesis (AB Students)

Oxidation of the Ultra-High Molecular Weight Polyethylene (UHMWPE) tibial inserts of total knee arthroplasty devices is a major factor underlying multiple modes of failure for these devices, including delamination, wear, and fracture. Previous research has demonstrated that oxidation of UHMWPE is driven by a high concentration of free radicals in the polyethylene. However, even new devices created with undetectable amounts of free radicals are oxidizing in vivo. One theory is that, in the absence of residual free radicals, oxidation is facilitated by absorbed species (e.g. lipids, ROS) delivered or exacerbated by contact stress. However, no method exists to comprehensively …

Compositional Optimization Of Amyloid-Graphene Oxide Nanohybrids For Biomaterials, Claire L. Drewery

Materials Engineering

Amyloid nanofibrils are natural materials capable of self-assembling into precise structures with tunable functionalities, while exhibiting excellent mechanical properties. In combination with highly conductive graphene oxide (GO), the 1-D amyloid nanofibrils and 2-D nanosheets of GO can produce a robust and bio-functional nanohybrid, hypothesized to exhibit multi-domain functional properties useful for enzyme sensing, water purification, drug delivery, and tissue scaffolding applications. Here, we examine the properties of an amyloid-graphene oxide nanohybrid film made with amyloids derived from hen egg white lysozymes in an attempt to explore the diverse toolbox of amyloid derivatives and establish ideal fabrication methods and formulations of …

Evaluation Of Human Umbilical Vein Endothelial Cells In Blood Vessel Mimics Through Changes In Gene Expression And Caspase Activity, Conor Charles Hedigan

Master's Theses

Blood vessel mimics (BVMs) are simple tissue engineered blood vessel constructs intended for preclinical testing of vascular devices. This thesis developed and implemented methods to characterize two of these components. The first aim of this thesis investigated the effect of cell culture duration and flow conditions on endothelial cell gene expression, especially regarding endothelial-to-mesenchymal transition (EndMT). A trend of decreased endothelial marker gene expression and increased mesenchymal marker gene expression would indicate EndMT. qPCR analysis revealed that increased cell culture duration did not result in EndMT, and in fact increased endothelial marker expression as cell culture duration increased. Disturbed flow …

Nano Fab Lab 63, Brian K. Deemer, Josh Clemons, Nick Brodine, Delaney Fitzsimmons

Mechanical Engineering

Lawrence Livermore National Laboratories (LLNL) has several steps in the production process for ceramic nanofiber tubes that they would like to improve - electrospinning, cutting, rolling, sealing and heat treating. We undertook the challenge to deliver LLNL with a semi-automated process that efficiently integrates the steps of cutting, rolling, and sealing to save time and improve control over end dimensions. In this document, we discuss the technical background of the manufacturing steps currently followed to create nanofiber tubes, identify which steps are incorporated in our prototype and explain how they will interface with one another, define the design requirements, present …

Two And Three-Dimensional Models For Material And Cells Interaction, Nam H. Nguyen

Doctoral Dissertations

Three-dimensional (3D) cell spheroid model has been long considered a better model to mimic in vivo physiology compared to two-dimensional (2D) cell culture model. Traditional 2D cell models provide a simple, convenient and quick technique for drug screening but fail to simulate the complexity and heterogeneity of cells in the in vivo environment. The last few decades have remarked substantial progress toward the advancement of three-dimensional (3D) cell cultures as systems which better mimic cellcell and cell-matrix interaction in the in vivo physiology. Nowadays, 3D cell models have been emerging, not only as an important approach in drug discovery and …

Cellular Modification And Artificial Cell Construction, Jimin Guo

Chemical and Biological Engineering ETDs

With all its complexities and different biofunctionalities, a cell is the basic structural and functional unit of all living organisms with the exception of viruses. In this dissertation, I demonstrated gain of function strategies of modifying mammalian cells using silicification and modular nanoparticle (NP) exoskeletons. In addition, I used a modular design concept to build a multifunctional artificial RBC system which can mimic the unique characteristics (e.g. shape, flexibility, the ability to carry oxygen, and long circulation times) of the native RBCs. Together, these cell modification or artificial cell construction strategies are expected to generate new mammalian cell-like structures with …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi S. Patel

University Scholar Projects

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Development Of A Sonically Powered Biodegradable Nanogenerator For Bone Regeneration, Avi Patel

Honors Scholar Theses

Background: Reconstruction of bone fractures and defects remains a big challenge in orthopedic surgery. While regenerative engineering has advanced the field greatly using a combination of biomaterial scaffolds and stem cells, one matter of difficulty is inducing osteogenesis in these cells. Recent works have shown electricity’s ability to promote osteogenesis in stem cell lines when seeded in bone scaffolds; however, typical electrical stimulators are either (a) externally housed and require overcomplex percutaneous wires be connected to the implanted scaffold or (b) implanted non-degradable devices which contain toxic batteries and require invasive removal surgeries.

Objective: Here, we establish a biodegradable, piezoelectric …

Investigating Virus Clearance Via Ph Inactivation During Biomanufacturing, Wenbo Xu

Biomedical Engineering Undergraduate Honors Theses

In the processing of biopharmaceuticals, viral clearance and viral safety are important for the development of monoclonal antibodies. Murine xenotropic leukemia virus (XMuLV) is one of the retroviruses, recommended by Food and Drug Administration (FDA) as a model virus for viral clearance via inactivation from therapeutics derived from Chinese hamster ovary cells (CHO). A robust and effective method was investigated to clear or inactivate endogenous viruses by low pH inactivation. The effects of different conductivity and inactivated time on XMuLV clearance was determined. Acetate buffer was prepared with different conductivity, and 2% XMuLV was spiked into acetate buffer. XMuLV virus …

Effect Of Polymer Composition Of Injectable Hydrogels On Programmable Release Of Methylene Blue, Mary Brandecker

Biomedical Engineering Undergraduate Honors Theses

Temperature sensitive hydrogels have been used as injectable hydrogels because the polymer solutions can be liquid at room temperature and gel at body temperature. Injectable hydrogels have been used in biomedical applications to deliver drugs and other small molecules throughout the body. Methylene Blue was used as the drug in this study for its antioxidant and neuroprotective properties. PluronicⓇ F127 (PF127) is a copolymer consisting of repeating units of polyethylene oxide and polypropylene oxide in the form PEO-PPO-PEO. PF127 in solution is a temperature sensitive hydrogel that transitions to a gel at body temperature at specific polymer compositions. A standard …

Design Of Microporous Membranes For The Development Of Brain-On-Chip Devices, Andre Figueroa Milla

Biomedical Engineering Undergraduate Honors Theses

Traumatic brain injuries (TBIs) are a major global health concern that have an economic impact of $60 billion in the United States in related costs annually. Developing drugs for TBI treatment is an approach that currently faces limitations involving the permeability of the blood-brain barrier (BBB). The BBB naturally limits molecules from reaching the brain as a protective mechanism against disease, acting as a barrier during drug delivery. Understanding the BBB mechanically and chemically following a TBI could potentially assist future studies to alleviate the symptoms and long-term effects of TBI by pharmaceuticals. The Mechanobiology and Soft Materials Laboratory (MSML) …

Suture-Less Trocar Site Closure Clip, Hares A. Patel

Electronic Theses and Dissertations

Introduction: Following laparoscopic surgery, there is a need, in many cases, to close trocar sites to prevent hernias. Currently, devices that exist on the market are suture based, but the lack of standardization in the suturing techniques together with the time-consuming nature of the procedure leads to the need for improvement in trocar site closure products. Trocar closure sites do not need to be fully closed on the fascial layer; rather, sufficiently blocking the hole at the abdominal wall can significantly reduce post-operative herniation. A retrospective study on trocar site herniation (TSH) after laparoscopic surgery indicates a TSH incidence …

Primitive Palms: A Density Study On The Impacts Of Harvesting Natural Materials For Construction Purposes On Sumak Allpa Of The Amazon Rainforest, Zachary Bull

Independent Study Project (ISP) Collection

In an effort to better understand how rural construction techniques affect a surrounding environment, this study combines a density test of the natural building materials used in the construction of a school on Sumak Allpa island of the Orellana Province in the Amazon basin of Ecuador. The focus of the study measures the density of the bamboo species Guadua angustifolia and the Panama hat plant Carludovica palmata on the island while noting a comprehensive compilation of the techniques and materials used in the building process. Using a mix of plots and transects, a comparison of harvested material to remaining material …

The Effect Of Defects And Surface Modification On Biomolecular Assembly And Transport, Haneen Martinez

Nanoscience and Microsystems ETDs

Nanoscale transport using the kinesin-microtubule (MT) biomolecular system has been successfully used in a wide range of nanotechnological applications including self-assembly, nanofluidic transport, and biosensing. Most of these applications use the ‘gliding motility geometry’, in which surface-adhered kinesin motors attach and propel MT filaments across the surface, a process driven by ATP hydrolysis. It has been demonstrated that active assembly facilitated by these biomolecular motors results in complex, non-equilibrium nanostructures currently unattainable through conventional self-assembly methods. In particular, MTs functionalized with biotin assemble into rings and spools upon introduction of streptavidin and/or streptavidin-coated nanoparticles. Upon closer examination of these structures …

Deswelling Induced Morphological Changes In Dual Ph And Temperature Responsive Ultra-Low Crosslinked Poly (N-Isopropyl Acrylamide)-Co-Acrylic Acid Microgels, Molla R. Islam, Maddie Tumbarello, L. Andrew Lyon

Engineering Faculty Articles and Research

Poly(N-isopropylacrylamide) microgels prepared without exogenous cross-linker are extremely “soft” as a result of their very low cross-linking density, with network connectivity arising only from the self-crosslinking of pNIPAm chains. As a result of this extreme softness, our group and others have taken interest in using these materials in a variety of bioengineering applications, while also pursuing studies of their fundamental properties. Here, we report deswelling triggered structural changes in poly(N-isopropylacrylamide-co-acrylic acid) (ULC10AAc) microgels prepared by precipitation polymerization. Dynamic light scattering suggests that the deswelling of these particles not only depends on the collapse of …

The Transcriptional Response Of Phanerochaete Chrysosporium And Trametes Versicolor To Growth On Stems Of Helianthus Argophyllus (Silverleaf Sunflower), Nadh Hamoud Alsubaie

Masters Theses

Traditional physicochemical and physicomechanical pretreatment technologies have improved the deconstruction of lignocellulose, but often require high energy inputs and added chemical reagents. Recent studies have demonstrated the use of white-rot fungi as alternative biological pretreatment agents that can mitigate these concerns. Although, white-rot fungi have been shown to grow on a variety of non-woody substrates, they have not been explored with respect to sunflower, which has the potential to provide raw materials for both biodiesel and bioethanol. In the present study, Silverleaf sunflower stems (Helianthus argophyllus) were used as substrates for the white-rot fungi Phanerochaete chrysosporium and Trametes …

Modification Of Lipid Microenvironments On Solid Support Structures For Use In Transmembrane Protein Assays, William J. Houlihan

Dissertations and Theses

Gamma-Secretase (γ-secretase) is a transmembrane protease of increasing interest, which has been shown to have significant connections to both cancer and Alzheimer’s disease. γ-secretase cleaves both Notch-1, a transmembrane signaling protein, and Amyloid precursor protein (APP), a transmembrane protein whose cleavage may result in the formation of β-amyloid plaques in the brain. Notch-1 and APP are widely studied proteins that have substantial impacts on the development and proliferation of cancer and Alzheimer’s disease, respectively. Notch-1 partakes in the signaling of apoptosis in damaged and mutated cells, thus its cleavage by γ-secretase within the plasma membrane has ramifications on cell growth …

Design And Mechanical Characterization Of 3d Printed Gradient Porosity Poly(Propylene Fumarate) Scaffolds, Andrea Felicelli

Williams Honors College, Honors Research Projects

Worldwide incidence of bone disorders and conditions, an already prevalent problem, is expected to double by 2020 from the rate in 2013 due to factors such as higher life expectancies and lower levels of physical activity. Every year in the United States, over half a million patients receive bone defect repairs, with costs greater than $2.5 billion. Current repairs are typically done with bone grafts, which are often costly and can result in added complications in the donor surgical site. Tissue engineering, a growing field that seeks to assist and enhance tissue defect repairs through the use of synthetic materials, …

The Production And Characterization Of Chitosan Based Microgels Using A Novel Microfluidic Device To Promote Cell Survival, Kaileen Shevchuk

Williams Honors College, Honors Research Projects

The purpose of this project is to synthesize and characterize perfluorocarbon modified methacrylamide chitosan (MACF) microgels produced with the use of a capillary-based microfluidic device. Since cell survival and development is highly related to particles physical properties, analysis of microgels set out to determine the particle’s physical properties. I hypothesize that the viscosity of the MACF polymer as well as the amount of photo initiator influence the physical properties of synthesized particles and as a result can generate particles with various features for cell culture in terms of shape, size, charge and swelling abilities. This hypothesis was validated through the …

Designing Biomimetic Implant Surfaces To Promote Osseointegration Under Osteoporotic Conditions By Revitalizing Mechanisms Coupling Bone Resorption To Formation, Ethan M. Lotz

Theses and Dissertations

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, …

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to develop …

Cell Surface Coatings For Mammalian Cell-Based Therapeutic Delivery, Pei-Jung Wu

Theses and Dissertations--Chemical and Materials Engineering

The cell plasma membrane is an interactive interface playing an important role in regulating cell-to-cell, cell-to-tissue contact, and cell-to-environment responses. This environment-responsive phospholipid layer consisting of multiple dynamically balanced macromolecules, such as membrane proteins, carbohydrate and lipids, is regarded as a promising platform for various surface engineering strategies. Through different chemical modification routes, we are able to incorporate various artificial materials into the cell surface for biomedical applications in small molecule and cellular therapeutics.

In this dissertation, we establish two different cell coating techniques for applications of cell-mediated drug delivery and the localization of cell-based therapies to specific tissues. The …

The Role Of The Mechanical Environment On Cd117+ Endothelial Cell Angiogenesis, Patrick Link

Theses and Dissertations

Angiogenesis is a complex process coordinating cell migration, proliferation, and lumen formation. Changes to the microenvironment regulate angiogenesis through mechanotransduction and cytokine signals. In pulmonary hypertension, something in the process becomes abnormal, resulting in changes to the microenvironment and the formation of a glomerulus of dysfunctional capillaries, called a plexiform lesion. Endothelial cells, expressing CD117 (CD117+ EC clones) increase in the plexiform lesions of pulmonary hypertension, independent of pro-angiogenic VEGF signaling. We hypothesize that the mechanical environment and the macromolecular composition of the extracellular matrix, both, contribute to the aberrant angiogenesis. When we changed the mechanical environment, we changed the …

Engineering The Alveolar Gas Exchange Barrier With Extracellular Matrix Coatings For Bioengineered Lungs, Bethany M. Young

Theses and Dissertations

Lower respiratory diseases are currently the third leading cause of death worldwide. For many end-stage patients with these diseases, there is no cure and a shortage of donor organs available for transplant. A promising solution is to design regenerative scaffolds or complete bioengineered lungs, using decellularized lung tissues as a template for regeneration. Recent advances in the field have made significant strides towards developing a transplantable lung. However, the current technology has not produced a functional lung for in vivo transplant due to immature gas exchange barriers. The mechanisms driving alveolar barrier maturation and role that extracellular matrix (ECM) plays …

Degradable Zinc Material Characteristics And Its Influence On Biocompatibility In An In-Vivo Murine Model, Roger J. Guillory Ii

Dissertations, Master's Theses and Master's Reports

Biodegradable stents based on zinc have been under development since their introduction in 2013. While metallic zinc is highly ductile, it unfortunately lacks the mechanical strength required for arterial stents. This has led to the development of an abundance of novel zinc-based materials, with the aim of improving the mechanical strength without sacrificing too much ductility. Although these materials are intended to function and slowly degrade within an artery, most zinc-based materials have been developed without deep consideration for their biological effects.

The present work explores the biological effects elicited by zinc-based materials implanted within the arterial system. The biological …

The Endocytotic Fate Of A Mesoporous Silica Nanoparticle Supported Lipid Bylayer Crispr Delivery Vehicle, Angelea Maestas-Olguin

2019 Award Winners

No abstract provided.

Chemically Modified Monolayer Surfaces Influence Valvular Interstitial Cell Attachment And Differentiation For Heart Valve Tissue Engineering, Matthew N. Rush

Nanoscience and Microsystems ETDs

As a cell mediated-process, valvular heart disease (VHD) results in significant morbidity and mortality world-wide. In the US alone, valvular heart disease VHD is estimated to affect 2.5% of the population with a disproportionate impact on an increasing elderly populous. It is well understood that the primary driver for valvular calcification is the differentiation of valvular interstitial cells (VICs) into an osteoblastic-like phenotype. However, the factors leading to the onset of osteoblastic-like VICs (obVICs) and resulting calcification are not fully understood and a more complete characterization of VIC differentiation and phenotypic change is required before treatment of valve disease or …

Towards An In Vitro Model Of Testing Osteoblast Cellular Function In Contact With Various Surfaces, Raheleh Miralami

Theses & Dissertations

Past studies have shown that the success of total joint replacements depends on the biocompatibility of orthopaedic materials, which can be improved by modifying the implant surface. However, the exact roles of these modifications and their effective mechanisms are poorly understood. The objective of this study was to develop and evaluate a model system to investigate the impact of nano-structured surfaces, produced by the ion beam-assisted deposition (IBAD) technique, on biomarkers of osteointegration using an in vitro model. The IBAD technique was employed to deposit zirconium oxide (ZrO₂), Titanium oxide (TiO₂), and Titanium (Ti) nano-films on …

Production And Biocompatibility Of Spider Silk Proteins In Goat Milk, Richard E. Decker Jr

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Due to its strength, flexibility, and biocompatibility, spider silk is a highly appealing material for applications in the medical field. Unfortunately, natural spider silk is difficult to obtain in large quantities because spiders are territorial and cannibalistic, making them impractical to farm. Synthetic spider silk proteins produced by transgenic hosts such as bacteria and goats have made it possible to obtain the quantities of spider silk needed to study it more fully and to investigate its potential uses. The spider silk proteins produced in our laboratory do not have an optimal purification method to remove all of the non-biocompatible contaminants …

Improving The Palatability Of Colonoscopy Preparations, Phuong Anh Hoang Nguyen, Darnell Leon Cuylear, Heather Elizabeth Canavan

Shared Knowledge Conference

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. The most reliable screening method of CRC is a colonoscopy which requires a 4-Liter polymer with electrolytes preparation. Two in five patients are non-compliant to their colonoscopy schedules, with many patients who abstain reporting refusal due to significant discomfort associated with this preparation. Furthermore, there are distinct gender differences in the tolerance of colonoscopy preparations in male and female populations. We hypothesize the differences in clinic are a result of toxic effects of the drug associated with poor mixing by individual patients. PEG, the drug, …