Biomedical Engineering and Bioengineering Commons^™

Experimental Evaluation Of Micro-Epidermal Actuators On Flexible Substrates, Courtney D. Bradley

Graduate Research Theses & Dissertations

Does embedding actuators in a flexible substrate increase their performance in hearing aids? What are the differences in damping experienced by actuators of different diameters and at different locations? At what frequency is peak acceleration achieved and what role does the size of the actuator and embedding it in a flexible substrate play? These questions will form the basis of this thesis. This work was done to develop a small non-invasive Band-Aid-©-like hearing aid. The novelty of this device requires a detailed analysis of piezoelectric actuators. This is a continuation of past students’ work on the topic. The main parameters …

Controlled Codelivery Of Mir-26a And Antagomir-133a With Osteoconductive Scaffolds To Promote Healing Of Large Bone Defects, Cole J. Ferreira

Masters Theses

Often caused by trauma or tumor removal, large bone defects frequently result in delayed or non-union. The current gold standard for treatment is autograft. However, due to limitations, such as the size and location of the defect, these cannot always be utilized. A common alternative to autograft is the use of BMP-2 with a collagen scaffold, however, this treatment is limited by numerous side effects. In recent years, genetic materials such as microRNAs (miRNAs) have offered possible alternative therapies. MiRNAs are small non-coding RNA molecules that generally range from 20-24 nucleotides, serve as repressors of gene expression, and are involved …

Mechanisms For Osteoblast And Osteocyte Initiation And Sustainment Of Bone Formation In Young-Adult And Aged Mice, Taylor Lynn Harris

McKelvey School of Engineering Theses & Dissertations

The cellular mechanisms for loading-induced bone formation, from osteocyte mechano-sensation to osteoblast-directed bone formation, are not well understood. Elucidating these mechanisms and identifying any processes that are disrupted in aged mice can aide in the development of new anabolic drugs for treating diseases like osteoporosis. This thesis begins by investigating the genes expressed by osteocytes following loading at an early mechanosensitive (4-hr) timepoint, and later at a bone-forming (day 5) timepoint. We demonstrated increases in Ngf and Wnt1 in osteocyte-enriched intracortical bone by laser capture microdissection and microarray analysis. These results were important in demonstrating the presence of Ngf in …

Computational Bone Mechanics Modeling With Frequency Dependent Rheological Properties And Crosslinking, Timothy G. Moreno

Master's Theses

Bone is a largely bipartite viscoelastic composite. Its mechanical behavior is determined by strain rate and the relative proportions of its principal constituent elements, hydroxyapatite and collagen, but is also largely dictated by their geometry and topology. Collagen fibrils include many segments of tropocollagen in staggered, parallel sequences. The physical staggering of this tropocollagen allows for gaps known as hole-zones, which serve as nucleation points for apatite mineral. The distance between adjacent repeat units of tropocollagen is known as D-Spacing and can be measured by Atomic Force Microscopy (AFM). This D-Spacing can vary in length slightly within a bundle, but …

Osteocyte Activity And Skeletal Muscle Relative Gene Expression Profiling After Short-Term Muscle Paralysis, Michelle Gelbs

Dissertations and Theses

Mechanical loading is essential for maintaining bone tissue. Reduced mechanical loading has been shown to have a negative effect on bone, and can result in the development of disuse osteoporosis. Disuse models of muscle inactivity and immobilization, like the Botox model used in this study, result in changes in the bone microarchitecture, the mechanisms behind which are not fully understood. In a previous four-week Botox disuse study, skeletally mature 20- week-old rats experienced degradation of intracortical bone, increased vascular porosity, and decreased osteocyte lacunar density in the tibiae. The focus of this study was to explicate a potential source of …

Optimal Parameter Values For Accurate And Repeatable Nanoindentation Of Human Trabecular Bone, Stephen Matthew Kmak

Master's Theses

Nanoindentation techniques have not been standardized for use on bone tissues, making comparison of bone material properties obtained via nanoindentation across studies difficult and unreliable. This study determined a set of optimal parameter values for thermal drift correction time, dwell time, and loading rate that can be used to obtain accurate and repeatable material properties from human femoral trabecular bone through experimentation and statistical analysis. All testing was conducted using a single nanoindenter on a single trabeculae, with the assumption that material properties within the individual trabeculae were internally consistent. Parameters not of interest during this study, such as ambient …

The Role Of Gene Transcription And Inflammatory Cytokines In Bone Fracture Repair, Brandon Alan Coates

McKelvey School of Engineering Theses & Dissertations

In most instances, the skeleton has a remarkable capacity for repair following injury. However, in 5 to 10% of patients, fractures fail to properly heal resulting in non-union. A need exists for a more comprehensive understanding of the complex biology of fracture repair, which involves the coordinated work of many cell types including osteoblasts, osteoclasts, and immune cells. Depending on the extent of injury, fractures will heal through either intramembranous bone formation, involving the direct formation of bone callus, or endochondral bone formation, featuring a cartilage intermediary prior to bone callus formation. Both processes begin with inflammation, which sets the …

Diffuse Damage Repair Mechanism In Bone, Leila Mehraban Alvandi

Dissertations and Theses

Bone microdamage is a result of fatigue, creep or ‘wear and tear’ caused by physiological activities and largely contributes to bone fragility. Bone, unlike engineered materials, has the ability to repair the microscopic cracking or microdamage through targeted, osteoclast-mediated bone remodeling. This capability is crucial for preservation of its structural integrity and quality; failure of the skeleton to effectively repair microdamage leads to accumulation of damage, which is one of the main contributors to bone fragility. Linear microcracks (50-100 µm) and diffuse damage (Dif.Dx) (sub-micron) are the two types of microdamage. Recent studies show that Dif.Dx repairs without bone remodeling, …

The Role Of Obesity And Dietary Fatty Acid Content In Regulating Humeral Bone And Cartilage Homeostasis, Lauren Votava

McKelvey School of Engineering Theses & Dissertations

Objective: The goal of this study was to investigate the effects of different dietary fatty acids in the context of diet-induced obesity on bone and cartilage in the humerus. It is known that obesity increases the severity of injury-induced osteoarthritis in the knee, however it is not fully understood what pathological changes have occurred due to diet alone¹. Additionally, while it is known that shoulder osteoarthritis has a link to obesity, the alterations in this joint are incompletely described.

Methods: In order to examine diet-induced changes in both bone and cartilage, this research utilized mice that had been …

Osteon Mimetic Scaffolding, Janay Clytus

Senior Theses

The purpose of this research is to provide an alternative to naturally derived bone grafts. There is a gap in the supply of donors and the demand of bone tissue. Artificial scaffold creation can work as an implant and decrease the shortage of bone grafts and increase the range of injuries that can be repaired. Current research focuses on optimizing mechanical properties such as porosity, improving vascularization using cells, and generating osteoconductivity. For osteodifferentiation, mesenchymal stem cells (MSCs) can differentiate into mesodermal lineages such as chondrocytes, osteoblasts, adipocytes, and tenocytes by supplementing cultures with lineage-specific soluble factors (Marchetti). Co-culturing ECFCs …

Nanocellulose Fibers As A Potential Material For Orthopedic Implantation Application, David Gregg Holomakoff

Electronic Theses and Dissertations

The field of biomaterials is of immense importance and will continue to grow and develop in the coming years. Novel materials, as well as new approaches for use of existing materials, are sought after now more than ever. Current metal orthopedic implants have an over engineered stiffness and Young’s modulus, causing a phenomenon called stress shielding. Metal implants absorb the majority of force typically exerted on bone and the osteocytes within. When osteocytes fail to sense mechanical forces bones become less dense and weaken, causing possible fracture and other complications. A new orthopedic material is needed matching Young’s modulus of …

Multi-Scale Assessment Of Bone Mechanics And The Mineral Phase Of Intramuscular Bone Of Atlantic Herring Fish, Svetlana Zeveleva

Dissertations and Theses

Bone tissue is a complex composite structure made up of a soft organic phase consisting of collagen I and non-collagenous proteins, and a hard inorganic phase consisting of mineral nanoplatelets. Given it’s compositional properties, bone is a unique stiff, tough, and strong biomaterial, making it exceptionally difficult to synthesize ex vivo. While the complete hierarchical structure may change with age and population, the basic building block components of mineralized collagen fibrils, are preserved. This study uses a model of intramuscular bone of the Atlantic herring fish, which present a simple structure, and no process of remodeling.

A multi-scale approach …

Densified Collagen-Fibril Biomaterials For Bone Tissue Engineering, Lauren E. Watkins

Open Access Theses

Millions of craniofacial bone defects occur annually as a result of trauma, congenital defects, disease, or tooth extraction. When present in the oral cavity, these defects are associated with adverse impacts on speech, mastication, and aesthetics. Thus, there is a clinical need for interventional strategies to restore and preserve alveolar bone mass to improve the success of future treatment options intended to reestablish functionality and aesthetics. Guided bone regeneration using bone grafts and a membrane represent the current standard of care for repairing alveolar bone defects, but face a number of limitations related to resorption time and structural integrity. Improvements …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

A Fractal-Based Mathematical Model For Cancellous Bone Growth Considering The Hierarchical Nature Of Bone, Stephanie Marie Suhr

Browse all Theses and Dissertations

The hierarchical structure of bone alone is not comprehensive enough to provide morphological explanation of how the size and arrangement of the trabeculae within cancellous bone affect load distribution, particularly concerning deterioration of bone in elderly patients. The collagen network and hydroxyapatite play a large role in defining the shape of trabeculae in cancellous bone despite that the arrangement and size is seemingly random. The growth of plates and rods in cancellous bone is mainly due to loading and stress lines within the bone, but mathematical predictive models can be developed using fractal analysis to show how bone may grow …

Analysis Of Citrate Content In Bone Using High Performance Liquid Chromatography, Matthew Konstantin Pysh

All Theses

Approximately 1.5 wt. % of bone is comprised of citrate molecules bound to the surface of apatite crystals. Furthermore, 80 to 90% of physiological citrate is contained within bone. Recently, interest in citrate has increased due to the potential of a citrate based method for estimation of postmortem intervals, time since death, of skeletal remains. The broad objective of this research was to develop and validate a High-Performance Liquid Chromatography (HPLC) method for quantitative and qualitative analysis of citrate in bone. An appropriate HPLC column and operating conditions for the detection of citrate were selected and subsequently used to analyze …

A Finite Element Analysis On The Viscoelasticity Of Postmenopausal Compact Bone Utilizing A Complex Collagen D-Spacing Model, Austin C. Cummings

Master's Theses

The nanoscale dimension known as D-spacing describes the staggering of collagen molecules, which are fundamental to the biphasic makeup of bone tissue. This dimension was long assumed to be constant, but recent studies have shown that the periodicity of collagen is variable. Given that the arrangement of collagen molecules is closely related to the degree of bone mineralization, recent studies have begun to look at D-spacing as a potential factor in the ongoing effort to battle postmenopausal osteoporosis. The theoretical models presented by previous studies have only opted to model a single collagen-hydroxyapatite period, so the creation of an intricate …

Piezoelectric Scaffolds For Osteochondral Defect Repair, Sita Mahalakshmi Damaraju

Dissertations

Osteoarthritis is one of the most prevalent causes of disability affecting nearly 27 million Americans. Osteoarthritis is caused when extensive damage occurs to the articular cartilage later spreading to the underlying subchondral bone, resulting in osteochondral defects. The current clinical therapies aim at regenerating the hyaline cartilage, but instead fibrocartilage forms at the osteochondral defect site, which is inferior in structure and function and fails to integrate with the surrounding tissue. A biomimetic scaffold, which can provide cues similar to the native extracellular matrix, may facilitate osteochondral defect repair. Articular cartilage and bone extracellular matrix have been shown to produce …

A Local, Sustained Delivery System For Zoledronic Acid And Rankl-Inhibitory Antibody As A Potential Treatment For Metastatic Bone Disease, Rohith Jayaram

Theses and Dissertations--Biomedical Engineering

Cancerous solid tumors can migrate and lead to metastatic bone disease. Drugs prescribed to reduce bone resorption from metastasis, such as zoledronic acid and the RANKL-inhibitory antibody Denosumab, cause side effects such as osteonecrosis of the jaw when delivered systemically. This project used two biocompatible materials, acrylic bone cement (PMMA) and poly(lactic-co-glycolic acid) (PLGA), to incorporate and sustain release of anti-resorptive agents. Results showed similar mechanical properties for acrylic bone cements loaded up to 6.6% drug by weight. Results showed sustained zoledronic acid release for 8 weeks from both systems, with PMMA releasing up to 22% of loaded drug and …

Human Hair Keratin Protein, Hair Fibers And Hydroxyapatite (Ha) Composite Scaffold For Bone Tissue Regeneration, Samuel Siyum

ETD Archive

The field of tissue engineering aims at promoting the regeneration of tissues or replacement of failing or malfunctioning tissue by means of combining a scaffold material, adequate cells and bioactive molecules. Different materials have been proposed for use as three-dimensional porous scaffolds for bone tissue engineering procedures. Among them, polymers of natural origin are one of the most attractive options mainly due to their similarities with the extracellular matrix (ECM), chemical versatility as well as typically good biological performance. In this study, two biocompatible composite scaffolds were developed from natural polymer by tissue engineering approach and tested in vitro. The …

The Effects Of Variation In Collagen D-Spacing On Compact Bone Viscoelasticity: A Finite Element Analysis, Miguel A. Mendoza

Master's Theses

The D-spacing that is characteristic of collagen and its structural arrangement was previously thought to be a constant value. Much research is revealing that it is actually a distribution of values in biological tissues. Recent ovine experimentation has also shown that the D-spacing distribution is significantly altered following estrogen depletion. While ewes contain some major biological differences between their human counterparts, they are an economical and robust large animal model for postmenopausal osteoporosis. So, the exploration of the possible implications that D-spacing has on the mechanical properties of the whole bone utilizing animal models and computational methods is warranted. Six …

Modeling The Zimmer Fitmore And Ml Taper Implantation, Tyler Kazuo Franklin

Master's Theses

With more young adults requiring total hip

arthroplasties the need for bone saving implants becomes

more important. The Zimmer Fitmore is a new bone saving

implant that utilizes an implantation technique that

reduces the damage to the muscle tissue allowing for

patients to have a short recovery time as well as a new

design that allows it to rest on the medial cortex. There

has been anecdotal evidence that this device leads to early

revision within six months of implantation due to failures

occurring in the medial cortex. The main goal of this

study was to computationally model the Zimmer …

Esem Analysis Of Mice Femurs With Varying Sost Levels, Patrick K. Mcclay

Biomedical Engineering

This project’s goal was to analyze the properties of the cortical femur on 100 mice bones from Lawrence Livermore National Laboratory. Analysis was limited to imaging which determined the ratio of bone volume to total volume (BV/TV) and osteocyte lacunae density. Mice were altered to knock out their SOST gene: a negative regulator of bone formation. Twelve groups were created to differentiate their treatment, duration, and phenotype. Transgenic (TG) mice had an overexpression of the SOST gene: they carried a bacterial artificial chromosome. Mice with limb defects (DEF) were the offspring of two TG mice and carried twice the amount …

Measuring The Strain Field Gradients On The Surface Of A Model Human Skull While Axially Loaded To Simulate Head-Loading, Matthew Graveley

Honors Theses

Head-loading is a means of transporting heavy loads accross rough, rural terrains practiced by many peoples in Third World countries. Years of practicing head-loading is said to result in increase spinal bone density and permantly grooved skulls. The most infamous people who practice head-loading are the porters of Nepal, who carry loads by means of a head sling straped across their foreheads, and South African women, who carry loads directly on their heads. To simulate and measure the instantaneous micro deformations occurring on the surface of the skull due to head-loading, a test procedure has been developed using a plastic …

Mechanical Characterization Of An External Fixator For Use In A Mouse Model, Thomas Albano

Honors Theses

Understanding the process of bone healing has become a fundamental part of medical research due to the approximately one million fractures which occur annually in the United States. The current methods of fracture fixation which use intramedullary rods, external fixators, and fracture plates are effective but not ideal. These fracture fixation methods can lead to mal-union or non-union due to improper callus formation stemming from inadequate fixation and support. When mal-union and non-union occur, the structural integrity of the bone becomes greatly sacrificed and the patient is left to deal with continual pain. Previous studies have suggested that the mechanical …

Bone Tissue Quality Determination Of Mice Through A Novel Reference Point Indentation Technique, Matin Lendhey

Dissertations and Theses

"Bone strength deteriorates with age; which increases the susceptibility to fracture. Current clinical techniques for the estimation of bone strength are largely Bone Mineral Density (BMD) based. However, toughness, which is the ability to resist crack growth, plays a critical role in bones‟ fracture resistance. Traditionally, toughness measurements involve large samples, obviating their use clinically. Recent data suggest that a reference point indentation approach provides a novel, localized measure of toughness from whole bones. In the current research, we evaluated the sensitivity of this method to discriminate small known differences in fracture toughness that exist between inbred mouse strains with …

Effects Of Estrogen Loss On The Vascular Porosity In Rat Cortical Bone, Jessica D Levy

Dissertations and Theses

"Osteoporosis is a skeletal disease that currently affects 10 million Americans, and is characterized by low bone mass and increased skeletal fragility (National Osteoporosis Foundation, 2011). Estrogen loss, which begins during menopause, is the leading cause of osteoporosis in women. Recent research has focused on changes in cortical bone microporosity due to estrogen loss, which is important for bone health; load-induced interstitial fluid flow within the lacunar-canalicular porosity surrounding osteocytes is thought to play an important role in bone maintenance, while the vascular porosity provides a pressure relaxation mechanism for the fluid flow in the lacunar-canalicular porosity. Recent high-resolution micro-CT …

The Development And Validation Of A Finite Element Model Of A Canine Rib For Use With A Bone Remodeling Algorithm., Scott J. Sylliaasen

Master's Theses

Studies are currently being performed to determine the effects of bisphosphonate treatments on the structure and density of bone tissue. One of the pathways for gaining a better understanding of the effects of this and other treatments involves creating a computer simulation. Theory suggests that bone tissue structure and density are directly related to the manner in which the tissue is loaded. Remodeling is the process in which bone tissue is resorbed in areas of low stress distributions, and generated in areas of high stress distributions. Previous studies have utilized numerical methods and finite element methods to predict bone structure …

The Development Of A Mesenchymal Stem Cell Based Biphasic Osteochondral Tissue Engineered Construct, Scott Maxson

All Dissertations

The ability of human articular cartilage to respond to injury is poor. Once cartilage damage has occurred, an irreversible degenerative process can occur and will often lead to osteoarthritis (OA). An estimated 26.9 million of U.S. adults are affected by OA. Osteochondral grafting is currently used to treat OA and osteochondral defects; however, complications can develop at the donor site and defect area. Osteochondral tissue engineering provides a potential treatment option and alternative to osteochondral grafting. The long term goal of this work is to develop a tissue engineered mesenchymal stem cell (MSC) based osteochondral construct to repair cartilage damage. …

Computer-Based Skeletal Age Assessment Using Hand/Wrist Radiographs In Children 8-18 Years Old, Zhihong Ni

Browse all Theses and Dissertations

Children's skeletons mature at different rates, and they can be affected by a variety of factors including disease, hormone imbalance or genetics. The assessment of skeletal maturity is a frequently performed procedure that allows the detection of hormonal, growth or genetic disorders. Several methods have been developed to estimate skeletal maturity. Most methods evaluate hand/wrist radiographs using indicators such as the ratios of various bone widths, the onset of the ossification of epiphysis and epiphyseal-diaphyseal fusion. Among those methods, the FELS method differs from others in the application of different grades to each indicator and the provision of a confidence …