Biomaterials Commons^™

Degradation Of Cobalt Chrome Molybdenum Hip And Knee Implants In Vivo And In Vitro, Peter William Kurtz

All Dissertations

Cobalt Chrome Molybdenum (CoCrMo) remains a popular material choice for femoral condyles in total knee arthroplasty and for acetabular liners in dual mobility total hip designs. CoCrMo has been phased out of conventional THA designs due to its correlation with adverse effects such as ALTR and ALVAL. It is less understood if the mechanisms (i.e. abrasive wear to the surface of the implant) that release metal ions into the surrounding tissue occur at similar rates as seen in conventional THA. Additionally, it is unknown what effect the secondary damage modes such as electrocautery damage and adhesive wear have on these …

Crevice Corrosion Mechanisms Of Cocrmo Alloys In Orthopedic Implants: Retrieval Analysis, Nano-Tribocorrosion And Cellular Responses, Hwaran Lee

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Mechanically assisted corrosion and non-mechanically (chemically) driven corrosion in modular junctions of orthopedic implants using cobalt-chromium-molybdenum (CoCrMo) alloys remain clinical concerns and may contribute to implant failure. The underlying corrosion mechanisms are not yet fully understood, leaving a critical research gap. We hypothesized that corrosion in modular junctions may be driven by aggressive local environments, including fretting, metal ion release (cobalt ion, Co²⁺), low pH and reactive oxygen species (ROS). This dissertation aims to (1) analyze corrosion modes and potential causes in modular junctions; (2) identify chemically driven corrosion modes on CoCrMo alloys using simulated inflammatory modular taper …

Deciphering And Translating Bioinspired Structures For Engineering Materials Design Via Computational Modeling And Machine Learning, Zhangke Yang

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Nature has evolved extraordinary structural materials—such as nacre, bone, and the mantis shrimp’s dactyl club—that achieve remarkable combinations of strength, toughness, and impact resistance. These properties arise from sophisticated synergies between structure and composition. Inspired by these biological systems, this dissertation presents a comprehensive investigation into bioinspired materials, uncovering fundamental mechanisms and providing guidance on designing materials with superior mechanical properties.

This dissertation begins by examining the "brick-and-mortar" structure of nacre, which informs the design of layered polymer-graphene nanocomposite films. Using coarse-grained molecular dynamics simulations, I elucidate mechanisms of dynamic wave propagation and energy dissipation in these systems, providing critical …

Development Of Rolipram Loaded Pgp Nanoparticles For Spinal Cord Injury Repair, Zhen Liao

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Spinal cord injury (SCI) leads to devastating neurological deficits due to primary mechanical damage and secondary injury mechanisms, including inflammation, oxidative stress, excitotoxicity, and inhibitory scarring, which collectively impede neural regeneration. One key aspect of SCI pathology is a significant reduction in cyclic adenosine monophosphate (cAMP) levels, primarily due to increased phosphodiesterase (PDE 4) activity. As a ubiquitous second messenger, cAMP regulates key signaling pathways, including protein kinase A (PKA) / cAMP response element-binding protein (CREB) and exchange protein activated by cAMP 2 (EPAC2). Therefore, restoring/increasing cAMP level is one of the major therapeutic strategies to reduce neurotrauma and restore …

Optimization Of Polymeric Micelles As A Delivery System For Crispr/Cas9 Ribonucleoprotein, Lucian Williams

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Clustered regularly interspaced short palindromic repeats (CRISPR) is an adaptive immune system in bacteria that has been harnessed to perform precise genetic modifications in mammalian cells. Among CRISPR-associated (Cas) proteins, Cas9 has emerged as a transformative tool in gene editing due to its simplicity, high specificity, and versatility compared to the other Cas proteins and gene-editing technologies. Despite its potential to cure genetic disorders, the clinical application of Cas9 has been hindered by challenges such as immunogenicity, off-target effects, and low delivery efficiency. To address these issues, this dissertation explores using polymeric nanoparticle systems to encapsulate and protect Cas9 and …

Multifunctional Peptides To Improve Nucleic Acid Delivery For Ovarian Cancer Treatment, Kharimat Lora Alatise

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RNA interference (RNAi) therapies, such as small interfering RNA (siRNA), offer a high-precision approach to reducing the expression of disease-promoting genes with minimal off-target effects. For aggressive diseases like ovarian cancer, RNAi therapy can serve as a robust treatment modality if delivered successfully. Over 70% of ovarian cancer patients are diagnosed in stages three and four, where the disease becomes more difficult to treat. High relapse rates and drug resistance in these stages demonstrate the need for novel strategies to sensitize tumors to chemotherapy, making siRNA a promising avenue for targeting resistance-associated oncogenes.

However, the delivery of siRNA remains a …

Investigating The Role Of Cd44 In Her2+ Breast Cancer Cells During Cancer Cell Redirection, Holly Caroline Jordan Campbell

All Dissertations

Despite a rise in survival rates of breast cancer patients due to advances in modern medicine, breast cancer is the most common type of cancer in women and is the second leading cause of cancer death in the United States. Early detection and a more personalized treatment of breast cancer has slowly improved patient outcomes. Nevertheless, there are impediments to better patient outcomes due to the complexity of the disease physiology. Therefore, there is a demand for a comprehensive understanding of cancer development as well as a need to understand tumor progression for enhanced therapies for patients.

Previous in vivo …

Expandable Tissue-Engineered Living Surgical Pulmonary Heart Valve For Pediatric Patients, Jacob M. Lautenschlager

All Theses

Cardiovascular disease is the most common cause of mortality in developed countries, with 607.74 million cases globally in 2020.^1,2 Advances in medicine have changed the current demographic suffering from heart valve disease into an aging population suffering from degenerative heart valve disease, creating a growing population treated by surgical or transcatheter intervention.^3-6 Current treatments of valvular heart disease are therefore directed toward valve replacements for the adult population, leaving a treatment gap for pediatric patients suffering from heart valve disease.^7-10

Congenital heart defects are defined as structural abnormalities of the heart or intrathoracic great vessels and are …

Contribution Of Collagen Type I To The Mechanical Properties Of Myocardial Tissues At The Micron Level, Adam Baker

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Collagen is a critical component of the organization and one of the key factors contributing to the mechanical stability of the myocardium. Where cardiomyocytes actuate to contract the heart and deliver blood to the lungs and the entire body, the local collagen network must be able to support the mechanical needs of the heart by enhancing rigidity, reducing the mechanical responsibility of cells, and increasing compliance to add loading capacity during diastole. At an organ-wide level, this has been measured and modeled in many ways. At the tissue level, the mechanical properties have been evaluated using techniques such as bi-axial …

Advancements Of A Breast Tissue Marker And Localization System, Azrin Jamison

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Breast cancer has become the most prominent cancer worldwide in women. Annual mammograms are encouraged for women of high risk to increase early detection allowing for lumpectomies rather than mastectomies to occur. Prior to a lumpectomy, a biopsy must be taken to determine if the tissue is cancerous, and a breast cancer biopsy marker (BBM) is left in the region of possible cancerous tissue. Wire localization has been the gold standard for localizing these BBMs. However, due to the reported patient discomfort and logistical inefficiencies faced by healthcare providers (HCP), non-wire localization solutions have been recently developed. This study aims …

Locally Injectable Peptide Hydrogel For Conversion Of Temozolomide And Codelivery Of Sirna In Glioblastoma Multiforme Treatment, Megan Pitz

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Traditional treatment methods for glioblastoma multiforme (GBM) are largely unsuccessful, with a 5-year survival rate of 5.6%. Temozolomide (TMZ), the only chemotherapy FDA-approved for GBM treatment, is a hydrophobic prodrug that is stable in an acidic pH and begins converting to its active form at a physiological pH of 7.4. However, complete conversion of TMZ is observed only at a higher pH, and only about 30% of administered TMZ reaches the central nervous system. Therefore, there is a need for new treatment methods that maximize TMZ delivery to and efficacy at the tumor site. Self-assembling peptides are a unique class …

Mesenchymal Stromal Cell Response To Degenerated Intervertebral Disc-Like Ph, Kyle Cannon

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Intervertebral disc degeneration (IVDD) has become increasingly prevalent and is a common contributing factor to low back pain. There are currently no clinical treatment options for IVDD that alleviate the symptoms of IVDD while simultaneously promoting repair of IVD tissue. One treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, the microenvironment of the degenerating IVD places significant stress on both native IVD cells and implanted cells. There are several questions that need to be addressed which may help further inform the development of efficacious intradiscal MSC therapies for IVDD. These questions include: 1) Do MSCs …

Novel Nucleus Pulposus Biomaterial Development And Low Field Mri Assessment For Intervertebral Disc Degeneration, Mario Krussig

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Intervertebral disc degeneration (IVDD) is a prominent pathology in the modern world that causes debilitating pain for many patients. The onset of IVDD occurs in the nucleus pulposus (NP). NP biomaterials will play a vital role in mitigating the progression of IVDD. Within this work, we sought to synthesize a solubilized extracellular matrix (ECM)-based NP biomaterial. Utilizing pepsin or urea extraction, bovine NP ECM was successfully solubilized (SBNPs). SBNP formulations were characterized biochemically, evaluated for cytotoxicity, and down-selected for front-running formulations. Leading candidate SBNPs were incorporated into an alginate bead biomaterial model to determine the potential bioactivity with human adipose-derived …

Tin-Silver As A Novel Biodegradable Metallic Biomaterial, Charley Goodwin

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The Essure device is a non-hormonal, minimally-invasive, permanent female sterilization implant, removed from the market due to an increase in adverse events, hypothesized to be caused by corrosion of the Sn-Ag component of the implant. The goals of this dissertation were to first develop implant retrieval methods for Essure devices and surrounding tissue, documenting signs of degradation and metallic degradation products, then to characterize the electrochemical behavior of Sn-Ag in biologically representative environments and finally, to assess the biological interaction of Sn-Ag. Retrieval analyses developed successful methods, qualifying the degree of corrosion, primarily of the Sn-Ag component and finding Sn …

Ti-6al-4v Β Phase Selective Dissolution: In Vitro Mechanism And Prediction, Michael A Kurtz

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Retrieval studies document Ti-6Al-4V β phase dissolution within total hip replacement systems. A gap persists in our mechanistic understanding and existing standards fail to reproduce this damage. This thesis aims to (1) elucidate the Ti-6Al-4V selective dissolution mechanism as functions of solution chemistry, electrode potential and temperature; (2) investigate the effects of adverse electrochemical conditions on additively manufactured (AM) titanium alloys and (3) apply machine learning to predict the Ti-6Al-4V dissolution state. We hypothesized that (1) cathodic activation and inflammatory species (H₂O₂) would degrade the Ti-6Al-4V oxide, promoting dissolution; (2) AM Ti-6Al-4V selective dissolution would occur …

Engineering Next-Generation Cardiovascular Therapies, Ryan Walker Barrs

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Cardiovascular diseases are the leading cause of death worldwide. Heart disease, in particular, accounted for 1 in every 5 deaths in the United States in 2021, representing a substantial public health burden that will require more effective treatment options to alleviate. Heart transplant surgery is currently the only option to completely restore cardiac function, but many patients die while waiting for a transplant due to a longstanding organ donor shortage. Thus, there is a dire need for accessible treatment options that can repair damaged hearts. Recent advances in tissue engineering and regenerative medicine have accelerated the development of therapies for …

Prevention And Reversal Of Elastin-Associated And Phosphate-Dependent Arterial Calcification Using Targeted Nanotherapeutics In Pre-Clinical Models, Fatema Tuj Zohora

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Vascular calcification can be life-threatening, involving calcium phosphate crystal deposits in the blood vessels. The calcification in the intimal layer of the arterial wall is usually associated with atherosclerotic plaque build-up that, in the advanced stage, harbors ‘dispersed’ and ‘spotty’ deposits of calcium phosphate crystals in the necrotic core of the plaque. In contrast, medial arterial calcification (MAC) can form independently of atherosclerosis and appears as ‘Railroad-like’ calcific deposits along degraded elastin lamellae in the medial layer of arteries. The mechanisms of such elastin-associated medial arterial calcification and potential therapies are the key concerns of this dissertation. MAC is common …

In Vitro And In Vivo Diabetic Models For Assessment Of Tissue Engineered Vascular Grafts, Juan Carlos Carrillo Garcia

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Diabetes has become one of the leading causes of lower-limb loss worldwide. Every 30 seconds, a person loses a limb due to diabetic-related vascular complications. About one-third of patients needing lower-limb bypass surgery have debilitated autologous vessels unsuitable for use, and no other good long-term options are available. These detrimental effects on the vasculature are caused mainly by the hyperglycemic and hyperlipidemic conditions derived from diabetes. Under these conditions, an increase in advanced glycation end products (AGEs) and reactive oxygen species leads to irreversible crosslinks of extracellular matrix proteins, accelerating vascular pathology through vascular stiffening, endothelial dysfunction, inflammation, atherosclerosis, fibrosis, …

Laser Inscribed Graphene Aptasensor For Detection Of Apple Stem Pitting Virus, Yifan Tang

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Apple stem pitting virus (ASPV) is a latent RNA virus that could cause significant loss to apple production; early-stage field diagnosis could reduce the economic loss caused by ASPV infection. Biosensor is a promising user-friendly detection tool that could transduce biological or chemical interactions into electric signals. Among various types of biosensors, aptasensor, which use aptamers as recognition elements show potential as a high throughput, in-field test. The goal of this thesis is to develop an electrochemical aptasensor testing system for ASPV detection. The quality control study of laser inscribed graphene (LIG) based working electrode of the biosensor was conducted …

3d Printing With Photopolymerizable Polyester Resins For Resorbable Medical Device Applications, Mathew Murphy Stanford

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In the past decade, the healthcare industry has seen a significant increase in the use of additive manufacturing (AM or “3D printing”) with subsequent improvement in clinical outcomes.As an exceptional AM technology, vat-photopolymerization (VP), often called stereolithography, can create complex structures and has thus been adopted for a range of biomedical applications including surgical guides, temporary implants, and resorbable tissue scaffolds.However, limitations remain in the availability of photopolymerizable resin materials with appropriate mechanical performance, biodegradability, and biocompatibility for application to resorbable medical devices.

The objective of this work was to employ novel photopolymerizable polyester-based macromers in the development of resorbable …

Highly Adherent Antimicrobial Coatings For Orthopedic Implants, Mikhail Bredikhin

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Fracture-related infections (FRIs) are the most devasting sort of complications associated with fracture fixation devices, as they lead to patients’ morbidity, prolonged hospitalization, amputations, and even death.External fixators additionally suffer from pin site infections (PSIs), which initiate at the skin entry points of the skin-metallic pin interface present in the external fixation of the damaged bones, often causing deep tissue infection and osteomyelitis. Small percutaneous pins, commonly known as Kirschner wires (K-wires), are used to treat complex fractures and deformities.They are drilled inside the diseased bone for the healing period and are left protruding outside the skin for fixation adjustments …

Development Of Enzyme-Responsive Polymersomes As A Drug Delivery System For Gm1 Gangliosidosis, Bipin Chakravarthy Paruchuri

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GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of β-galactosidase (βgal) and subsequent accumulation of GM1 ganglioside in lysosomes. The rare nature of this disorder presents challenges with prognosis and treatment. Enzyme replacement therapy (ERT) can effectively treat systemic deficiencies, but the intravenously administered enzyme cannot cross the blood-brain barrier (BBB) to treat the central nervous system. A delivery system to encapsulate and deliver the enzyme can facilitate enzyme transport across the BBB with suitable surface modifications. One of the pathological aspects of GM1-affected cells is the upregulation of the lysosomal enzyme hexosaminidase A (HexA). In this dissertation, …

Tissue-Engineered Living Pulmonary Valve For Young Adult Patients, Erica Hoskins

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Cardiovascular disease (CVD) is a non-communicable disease responsible for 659,000 deaths annually in the United States. While CVD can affect all components of the cardiovascular system, heart valve disease is responsible for 25,000 deaths yearly. Of specific interest is the pulmonary valve since there is limited research on resolving pathologies that affect it. Like the aortic and mitral valves, common pathologies include stenosis, regurgitation, and atresia. Notably, the pulmonary valve requires repair and replacement in pediatric patients and young adults due to congenital disabilities. Even with technological advances in valve replacements, limitations still present themselves for use with younger patients …

Insect Antennae As Bioinspirational Superstrong Fiber-Based Microfluidics, Griffin J. Donley

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Nature is frequently turned to for inspiration for the creation of new materials. Insect antennae are hollow, blood-filled fibers with complex shape, and are cantilevered at the head. The antenna is muscle-free, but the insect can controllably flex, twist, and maneuver it laterally. To explain this behavior, a comparative study of structural and tensile properties of the antennae of Periplaneta americana (American cockroach), Manduca sexta (Carolina hawkmoth), and Vanessa cardui (painted lady butterfly) was performed. These antennae demonstrate a range of distinguishable tensile properties, responding either as brittle fibers (Manduca sexta) or strain-adaptive fibers that stiffen when stretched (Vanessa cardui …

Single Asperity Fretting Corrosion Of Traditional And Additively Manufactured Metallic Biomaterials: Quantitative Analysis From Acetabular Tapers To Micron And Nanometer Scale Tribocorrosion, Annsley Mace

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Mechanically assisted crevice corrosion (MACC) of metallic biomaterials continues to be a significant degradation mode. This is, in part, due to a lack of understanding of fundamental micron- and sub-micron scale mechanisms of metal degradation in biological environments. Metal-metal (or metal-hard) load bearing surfaces of hip arthroplasties are subjected to fretting crevice corrosion (FCC, one form of MACC). Current work in tribocorrosion involves large contact area tests with multiple asperities, with a distribution of load and wear that changes over time. A more systematic and controlled study of the FCC micro- and nanomechanics is needed.

Therefore, the goal of this …

Synthesis Of Monodisperse Nanoscintillators At High Temperatures For Biomedical Relevant Applications, Eric Zhang

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Luminescent sub-100 nm particulates continuously generate immense research interest in the biomedical field for imaging, theranostics, and optogenetics. Conventionally, upconversion nanoparticles or UV activated semiconductors are studied, however these materials are limited by biological barriers such as the skin which reduces the penetration depth of these excitation sources, tissue's auto- fluorescence, and toxicity. One approach to overcome these challenges is to use nanoscintillators (sub-100 nm materials that can generate visible light using high energy excitation sources such as x-rays) which can generate light locally to the human body. Numerous scintillators have been reported since the discovery of x-rays from the …

Influencing The Inflammatory Response Through Multi-Scale Geometry, Antibiotic Release, And Fluid Management In A Textile-Based Biomaterial Wound Dressing, Elizabeth Gianino

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The total population of diagnosed and undiagnosed diabetes mellitus in the United states is expected to rise by 54% between the years of 2015 and 2030 contributing to $200 billion in health care expense. The exponential rise in common diabetic wounds, such as diabetic foot ulcers, puts a large population at risk for complications such as infection, amputation, and even death. Peripheral neuropathy leading to late diagnoses, patient non-compliance, and lack of holistic treatment options all contribute to complications with the incidence of new ulcer formation after treatment reaching 50%. This work explores the design, development, and in vitro evaluation …

Time-Lapse Observation Of Sarcomeric Addition In Hypertrophic Models Based On A Tissue Like Cardiomyocyte Culture, Ailin Wei

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Cardiac hypertrophy is the response of the heart to increased mechanical stress exerted on the heart. In a hypertrophic heart, the muscles elongate or/and thicken with cardiomyocytes growing sizes. It is assumed that cardiomyocytes elongate by adding sarcomeres in series; the cardiomyocytes thicken with the addition of sarcomeres in the parallel position.

In this study, a tissue-like culture model was achieved with step-like ICDs. Uniaxial static stretch has been applied to our unique culture model for studying mechanical-load-induced cardiac hypertrophy. Hypertrophic responses of these cardiomyocytes have been confirmed on transcriptional and translational levels in our tissue-like model. The two-photon excitation …

Development Of Solution Blow Spun Nanofibers As Electrical And Whole Cell Biosensing Interfaces, Craig Levar Miller

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Infectious pathogens place a huge burden on the US economy with more than $120 billion spent annually for direct and indirect costs for the treatment of infectious diseases. Rapid detection schemes continue to evolve in order to meet the demand of early diagnosis. In chronic wound infections, bacterial load is capable of impeding the healing process. Additionally, bacterial virulence production works coherently with bacterial load to produce toxins and molecules that prolongs the healing cycle. This work examines the use of nonwoven polymeric conductive and non-conductive nanofiber mats as synthetic biosensor scaffolds, drug delivery and biosensor interface constructs. A custom-made …