Master of Science (MS), Ohio University, 2013, Mechanical Engineering (Engineering and Technology)

In this study I investigate the changes in the mechanical properties of trabecular bone due to altered loading. The bone samples come from porcine mandibular condyles of treated and untreated pigs from a previous study. The treated animals wore one of two kinds of occlusal splints which presumably altered the loading on the mandibular condyle. This study uses micro-CT images of the mandibular condyles to render a finite element mesh of the trabecular structure. Uniaxial compression was then simulated with finite element analysis to determine the apparent modulus of the bone samples. It was found that one of the splinting treatments significantly reduced the apparent modulus and bone volume fraction in the central region of the mandibular condyle. This study also used experimental uniaxial compression tests of fresh bone samples to validate the finite element model. It was found that there was 30% agreement between the finite element model and the experimental results for the apparent modulus in the anterior-posterior, and medial-lateral directions.

Committee: John Cotton (Advisor) Subjects: Biomechanics

MS, University of Cincinnati, 2022, Engineering and Applied Science: Chemical Engineering

Dexamethasone (DEX) is used to treat the aggressive inflammation that is associated with diseases like diabetic macular edema, diabetic retinopathy, uveitis, and age-related macular degeneration (AMD). Prolonged use of DEX can lead to side effects like cataracts and elevated intraocular pressure (IOP). Chronically elevated IOP can lead to the development of glaucoma, a disease characterized by damage to the optic nerve. This glucocorticoid-induced ocular hypertension (GC-OHT) occurs in ~40% of patients without glaucoma and ~90% of patients with primary open angle glaucoma (POAG). GC-OHT is thought to be caused by the ability of DEX to remodel the extracellular matrix (ECM) and actin cytoskeleton on trabecular meshwork cells, which drain the aqueous humor (AH). IOP is controlled through the production and drainage of AH. To reduce the GC-OHT caused by DEX while still allowing for an efficacious treatment, this study tests the effect of dose of DEX, and a combination therapy of DEX and Ripasudil (RIP), on the phenotype and genotype of TM cells. RIP is a Rho kinase inhibitor that can reduce IOP, by affecting the actin cytoskeleton of TM cells. TM cells were treated with various doses of DEX and combination of DEX and RIP for 6 days. The phenotype was tested using FITC-dextran permeability, collagen contractility and actin staining. Each of these assays showed a dose-dependent effect of DEX on the TM cell phenotype. Permeability decreases, contractility increases, and the average amount of actin per cell increases in response to an increasing dose of DEX. RIP was able to reverse these effects in contractility and actin levels but not permeability. TM cells dosed with low (10 nM) and high (10 µM) DEX were subject to RNA sequencing. Differential gene expression analysis was done between control and 10 nM DEX (Group A), control and 10 µM DEX (Group B), and 10 nM and 10 µM DEX treatments (Group G). Pathway enrichment analysis was done on the differentially expressed genes ( (open full item for complete abstract)

Committee: Yoonjee Park Ph.D. (Committee Member); Winston Kao Ph.D. (Committee Member); Greg Harris Ph.D. (Committee Member) Subjects: Chemical Engineering

Doctor of Philosophy, University of Akron, 2022, Integrated Bioscience

Opioids have become one of the most misused classes of prescribed medication. Synthetic opioids (e.g., fentanyl) have been responsible for most opioid overdose deaths since 2017. As this epidemic shows no signs of slowing, it is imperative to study the effects of opioids on various aspects of health including bone maintenance. Endogenous opioids (e.g., met-enkephalin) are involved in osteogenesis and bone remodeling. Exogenous opioids can interfere with bone maintenance directly through binding to osteoblasts, limiting bone formation, or indirectly through a cascade of effects limiting sex hormone production. To understand how opioids affect bone microarchitectural and biomechanical properties we first examine bone microstructure throughout the human lifespan to see natural changes occurring without the effects of opioids. Using both Synchrotron Radiation micro-Computed Tomography and confocal laser microscopy, we found bone and lacunar volume fractions to decrease with advancing age while pore diameter increased in the anterior midshaft femur. After finding how bone changes with age under normal circumstances, we sought to examine how prolonged opioid administration affected trabecular microstructure in a model organism (rabbit). We used μCT to examine the proximal tibia by anatomical quadrant (e.g., anterior, posterior). We found that morphine animals had greater bone volume fraction and less trabecular separation than controls. Fentanyl animals had significantly thicker trabeculae and increased trabecular spacing than controls. Detected differences by anatomical region followed the same overall pattern, suggesting biomechanical or anatomical variation rather than due to opioids. We finally examined overall bone strength in a non-weight bearing bone (rib) of the rabbit using uniaxial compression testing to determine how opioids affect overall mechanical competency. We found no difference in mechanical variables between opioid and control groups. Only rib span leng (open full item for complete abstract)

Committee: Brian Bagatto (Advisor); Janna Andronowski (Committee Co-Chair); Henry Astley (Committee Member); David Cooper (Committee Member); Christine Dengler-Crish (Committee Member); Nita Sahai (Committee Member) Subjects: Biology; Biomechanics; Histology; Pharmaceuticals; Physiology

Doctor of Philosophy, The Ohio State University, 2017, Anthropology

The objective of this research was to test the hypotheses that ontogenetic patterns of change in tibial subchondral trabecular and cortical bone microstructure are age and condyle site-specific due to differential loading associated with changing joint kinetics and body mass. High-resolution computed tomography (HR-CT) images were acquired for 31 human tibiae, ranging in age from 8 to 37.5 years. The skeletal samples are from Norris Farms #36 site, a cemetery mound in the central Illinois River valley associated with the Oneota culture, dating to A.D. 1300. This bioarchaeological sample was chosen for this study because of its cultural and biological homogeneity, high number of subadult individuals, extensive archaeological context, and excellent preservation. Proximal epiphyses were digitally isolated for analysis as regions of interest (ROIs) using Avizo Fire 6.2 and 8.1.1. 3D resolution-corrected morphometric analysis of subchondral bone architecture was performed for 11 cubic volumes of interest (VOIs) using the BoneJ plugin for ImageJ. VOIs were positioned within and between the tibial condyles within the epiphyseal region. The analysis of the subchondral cortical plate was accomplished through dual-threshold cortical masking. Ontogenetic patterns in the epiphysis of the proximal tibia were described using eight 3D morphological parameters: bone volume fraction (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular spacing (Tb.Sp), structure model index (SMI), connectivity density (Conn.D), degree of anisotropy (DA), trabecular number (Tb.N), and cortical thickness (Ct.Th) in the subchondral cortical plate. Kruskal-Wallis and Wilcoxon signed rank tests were used to examine the association between region, age, and each of the eight structural parameters. For analysis, individuals were divided into four age categories: child, adolescent, young adult, and middle age. The findings of this study indicate that age-related changes in mechanical loading have (open full item for complete abstract)

Committee: Samuel Stout PhD (Advisor); James Gosman M.D, PhD (Committee Member); Mark Hubbe PhD (Committee Member); Clark Larsen PhD (Committee Member); Scott McGraw PhD (Committee Member) Subjects: Aging; Anatomy and Physiology; Archaeology; Behavioral Sciences; Biology; Biomechanics; Evolution and Development; Microbiology

Doctor of Philosophy, The Ohio State University, 2016, Anthropology

The significance of the microstructural interface between trabecular and cortical bone in the long bone metaphyses as a mechanically-adapted feature of skeletal morphology is largely unexplored, despite the role of these structures as critical for the transmission of axial loads from the trabecular network to the cortical diaphysis. These cortical-trabecular junctions (CTJs) are studied here within the context of bone ontogeny and from the perspective of mechanobiology, which seeks to interpret skeletal morphology as a product of its mechanical-functional demands. Aligned to the theoretical paradigm of bone functional adaptation, which states that bone adapts to its mechanical environment during life, this study tests several hypotheses regarding various associations between body mass and age on the one hand and various measures of CTJ structure on the other, including elements of cortical-trabecular connectivity and bone volume distribution. Anatomical site variability and mechanical adaptability in CTJ ontogeny was further addressed by examining these skeletal features in two separate skeletal elements with vastly different mechanical functions. This study was performed conducted using the Norris Farms (NF) No. 36 skeletal series, an archaeological sample of skeletons derived from a late-prehistoric group of Oneota Native Americans living in present day west-central Illinois ca. 1300 A.D. Micro-computed tomography was used to acquire high-resolution images of NF adult and sub-adult tibiae and humeri for non-invasive and non-destructive analysis of internal bone microstructure. Two computer image analysis programs (Avizo Fire 8.1.1 and ImageJ 1.49v) were used to isolate and quantify volumes of interest, and all statistical analyses were carried out in SPSS v.22. Results show a complicated picture of CTJ ontogeny in which mechanical adaptability appears to be an important driver of CTJ structural development, but not to the exclusion of other, less clear factors. (open full item for complete abstract)

Committee: Clark Larsen (Advisor); James Gosman (Committee Member); Amanda Agnew (Committee Member); Paul Sciulli (Committee Member); Sam Stout (Committee Member) Subjects: Anatomy and Physiology; Archaeology; Biomechanics; Human Remains; Physical Anthropology; Soil Sciences

Master of Science (MS), Ohio University, 2014, Mechanical Engineering (Engineering and Technology)

This study improves the agreement between two stiffness measurement techniques of trabecular bone harvested from porcine mandibular condyles. The previous method of Zaylor (2013) measured stiffness with digital finite element and experimental compression tests using 2 mm bone cubes. The current study improves the agreement between methods by examining the effect of sample size using 3 mm and 4 mm cubes, the effect of strain range used in compression tests, and investigating the geometric accuracy of the digital finite element models. It was found that larger specimens improved the stiffness agreement in mediallateral, and superior-inferior directions of the condyles, (R² > 49). The agreement was not affected by the strain limits of 0.4-0.5%, 0.5-0.6%, and 0.4-0.6%. The average digital cube lengths were 2% smaller than the physical lengths. The improved agreement justifies digital modeling of trabecular bone to measure the stiffness of mandibular condyles.

Committee: John Cotton (Advisor) Subjects: Biomedical Engineering; Mechanical Engineering

Doctor of Philosophy, The Ohio State University, 2011, Biomedical Engineering

Primary open angle glaucoma (POAG) is the second leading blind disease in the world. The pathological mechanism of glaucoma has been still debated. The general representative symptom of glaucoma is the abnormally increased intraocular pressure (IOP), which causes optic nerve damage and permanent vision loss. According to previous research, the breakdown of production and clearance of aqueous humor (AH) increases the IOP. The specific ocular tissue called as a “trabecular meshwork (TM)” in the AH outflow drainage system is believed to play an important role in the regulation of IOP in the normal range from 15mmHg to 22mmHg. Clinical treatments of glaucoma are to lower the IOP to the normal range. In general, the invasive surgical techniques such as “trabeculectomy”, and “laser trabeculoplasty” are performed with relevant medications. Although the coagulation of tissue by laser based surgeries is less invasive than surgical removal, patients are still exposed to the post-operative risks such as tissue coagulation, inflammation, cornea injury, and cataract. These may cause secondary visual loss. In this work, due to the complex morphology of TM tissue and interrelated parameters involved in the IOP regulation, the key factors governing the outflow facility are investigated using multi-disciplinary approaches. First, the perfusion test was conducted to examine the effect of low fluence diode laser (wavelength: 830nm) which generates the non-invasive level of energy on the hydraulic resistivity of in vitro cultured TM monolayer on the solid porous membrane. The expression of heat shock protein upon low fluence laser treatment was also assessed. The dose-dependent effect of glucocorticoid drug (dexamethasone) was investigated using the electrical impedance spectroscopy. To take into account the three dimensional (3D) porous morphology of TM, polymer based micro/nanofibrous membranes mimicking the in vivo-like environment of natural TM was constructed by combining an arra (open full item for complete abstract)

Committee: Yi Zhao PhD (Advisor); Cynthia Roberts PhD (Other); Deborah Grzybowski PhD (Other); Mark Ruegsegger PhD (Other) Subjects: Biomedical Engineering

Doctor of Philosophy, The Ohio State University, 2007, Anthropology

The goal of this research was to study trabecular bone microarchitecture during growth and development, producing new quantitative and structural knowledge about the development and remodeling of normal trabecular structure as demonstrated in a subadult archaeological skeletal sample from the Late Prehistoric Ohio Valley. Trabecular bone microarchitecture has a predictable relationship to functional and external loading patterns applied throughout ontogeny and maturity. Relatively little research has been directed toward the structure of and variation in trabecular bone during ontogeny, creating a deficiency in the foundation upon which trabecular bone adaptation can be used for bioarchaeological inferences. This research project tests hypotheses characterizing the temporal sequence and variation in trabecular bone volume fraction and degree of anisotropy as a reflection of growth and development, as associated with the timing and acquisition of normal functional activities (initial and maturation of bipedal gait), and as associated with changing body mass. A selected skeletal sample from the Late Prehistoric site (A.D. 1200-1300) of SunWatch Village consisted of 37 subadult and three young adult proximal tibiae. The sample as a whole, as well as four maturity stage-related groups, was analyzed. The analyses consisted of nondestructive microCT scanning of the proximal metaphyseal tibia visually demonstrating the microarchitectural trabecular structure, and quantitative 3-D structural analyses measuring bone volume fraction, degree of anisotropy, trabecular thickness, and trabecular number. Bone volume fraction and degree of anisotropy are highest at birth, decreasing to a low value at one year of age, and then gradually increasing to the adult range around six to eight years of age. Trabecular number is highest at birth and lowest at skeletal maturity; trabecular thickness is lowest at birth and highest at skeletal maturity. The results of this study provide quantit (open full item for complete abstract)

Committee: Clark Larsen (Advisor) Subjects: Anthropology, Physical

Doctor of Philosophy, Case Western Reserve University, 2011, EMC - Mechanical Engineering

It has been suggested that bone remodeling targeted to microscopic tissue damage can impair trabecular bone biomechanical properties, potentially modifying overall bone strength. In this study, we evaluate microscopic tissue damage and remodeling cavities using experimental and computational methods. Cyclic loading experiments were performed on isolated rat caudal vertebrae (n=24) to evaluate the progression of microscopic tissue damage in trabecular bone in-vitro. Vertebrae were potted in bone cement and subjected to cyclic loading between 0 – 260N. Cyclic loading was terminated at secondary and tertiary phases of the creep-fatigue curve. Trabecular microfracture was the primary form of damage in trabecular bone and the number of microfractures increased with the amount of cyclic loading. Only small amounts of microscopic tissue damage were observed in the cortical shell, demonstrating that the damage occurs in trabecular bone prior to complete fracture of vertebrae. Modifications to the rat tail loading model developed by Chambers and colleagues were considered to evaluate the feasibility of using the model to generate microscopic tissue damage in trabecular bone without fracturing the vertebrae in-vivo. Protocols were developed to apply cyclic loading to caudal 8th vertebrae (C8) in-vivo (n=20) or in-situ (n=15). Two pin types: smooth and threaded, two pin sizes: 1.6mm and 2.0mm dia. and four time points after the surgery: 0, 1, 2 and 4 weeks were considered. Our results indicated that the rat tail loading model may not be used for generating microscopic tissue damage in trabecular bone in-vivo. Finite elements models of idealized trabeculae were generated to determine a potential range for stress concentrations factors of remodeling cavities. Two types of trabecula: rod-like and plate-like and two types of loading conditions: pure tension and pure bending were considered. Finite element models of two rod-like and three plate-like rat trabeculae were generated (open full item for complete abstract)

Committee: Christopher Hernandez (Committee Chair); Clare Rimnac (Committee Member); Joseph Mansour (Committee Member); Eben Alsberg (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Mechanical Engineering

Doctor of Philosophy, Case Western Reserve University, 2011, Anatomy

The vertebral column is a complex anatomical structure in terms of form and function, and the majority of the loads applied to it during locomotion pass through the bodies of the vertebrae. Spontaneous vertebral fractures are a common skeletal pathology in humans, and are linked to low bone mineral density. In contrast, spontaneous vertebral fractures have not been reported in apes, even in cases of extremely low bone mineral density. Given these observations, it is likely that there is a structural difference in the vertebral bodies among humans and apes that causes humans to be more susceptible to spontaneous vertebral fracture. The focus of this study was to determine how the structure of the vertebral body in terms of gross morphology, trabecular microarchitecture and shell thickness differed among humans and apes, and whether these differences were related to body mass, locomotion and strength of the vertebral body. Humans have larger vertebral bodies along the entire length of the vertebral column than would be expected for body mass, and the vertebral bodies increase in size along the length of the vertebral column similar to the much larger gorilla. However, when vertebral body size is normalized within the vertebral column, there are no differences among the species. Additionally, although humans have large vertebral bodies, they are still weaker than would be expected for their size. Humans have lower trabecular bone volume fraction than gibbons and African apes, and displayed a negative correlation between bone volume fraction and degree of anisotropy in the ventral vertebral body unlike the other hominoids. Humans have thinner vertebral shells than would be expected for their body mass and vertebral body height. The combination of tall vertebral bodies containing unsupported columnar, craniocaudally oriented trabeculae that do not support the thinner than expected vertebral shell may be the structural differences in vertebral bodies that account for the (open full item for complete abstract)

Committee: Scott Simpson (Committee Chair); Christopher Hernandez (Committee Member); Darin Croft (Committee Member); Bruce Latimer (Committee Member) Subjects: Anatomy and Physiology

Master of Sciences (Engineering), Case Western Reserve University, 2010, EMC - Mechanical Engineering

Structurally intact trabecular bone allografts are an attractive tissue choice due to their osteoconductive structure and ability to provide some mechanical stability to the graft site. To prevent disease transmission, allograft bone is subjected to gamma sterilization. Irradiation has been shown to reduce the mechanical properties of cortical bone and change micro-damage accumulation in dense bovine trabecular bone. This study seeks to assess the effect of gamma sterilization on the yield properties of human trabecular bone across a range of bone volume fractions. Cylindrical human trabecular specimens (distal and proximal) irradiated to 29.45kGy were compared with non-irradiated controls. Specimens were compressed to past yield and analyzed using histological sections. Mechanical and histological analysis showed no differences between irradiated and control specimens. This suggests that structurally intact trabecular bone allograft, across a range of volume fractions, does not experience significant degradation in strength, stiffness or damage accumulation following gamma irradiation.

Committee: Christopher Hernandez (Advisor); Claire Rimnac (Committee Member); Joseph Mansour (Committee Member) Subjects: Engineering; Mechanics

Doctor of Philosophy, The Ohio State University, 2013, Anthropology

This study examined microstructural properties of bone in individuals from the ancient Peruvian polity of the Chiribaya. The three sites include San Geronimo, El Yaral, and Chiribaya Alta which represent fishing, agricultural and elite lifestyles, respectively. The purpose of the study was to test four hypotheses: 1.Variability in relative area measurements due to differential loading throughout the skeleton exist, 2. Differences in histomorphometric areal and length measurements exist among different age groups due to the effects of increasing age, 3. Differences in histomorphometric areal and length/perimeter measurements exist among individuals from Chiribaya Alta, El Yaral and San Geronimo due to variation of diet and general subsistence level activities, 4. Sex differences exist in histomorphometric areal and perimeter/length measurements in the Chiribaya sample. Sections were removed from the rib and clavicle at midshaft, and from the standardized site of clinical biopsy in the iliac crest. Data collection included areal and perimeter/length measurements on cortical bone in the rib and clavicle and a combination of cortical and trabecular bone in iliac crest specimens. Variables examined include total area (Tt.Ar.), cortical area (Ct.Ar.), endosteal area (Es.Ar.), relative cortical area (Rel.Ct.Ar.), periosteal perimeter (Ps.Pm.) and endosteal perimeter (Es.Pm.) in rib and clavicle samples. In iliac crest sections, measurements of were taken of: total area of section (Tt.Ar.), the area containing trabecular bone (Es.Ar.), cortical area (Ct.Ar.), relative cortical area (Rel.Ct.Ar.), area of trabecular bone (Tb.Ar.), relative trabecular area (Rel.Tb.Ar.), mean trabecular width (Tb.Wi.), total section diameter (Tt.Dm.), total cortical diameter (Ct.Dm.) and marrow cavity diameter (Es.Dm.). This study included variables measured on 62 rib sections, 54 clavicle section and 62 iliac crest sections of males and females of varying ages. Intra-skeletal variability was e (open full item for complete abstract)

Committee: Sam Stout (Advisor); Paul Sciulli (Committee Member); Clark Spencer Larsen (Committee Member); Mark Hubbe (Committee Member) Subjects: Histology; Physical Anthropology