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Bone

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Full-Text Articles in Engineering

Experimental Evaluation Of Micro-Epidermal Actuators On Flexible Substrates, Courtney D. Bradley Jan 2023

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 Mar 2022

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 Aug 2021

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 Mar 2021

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 Jan 2021

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 Oct 2020

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 May 2020

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 Jan 2020

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, …


Structurally Supported Cell-Laden Scaffolds For Bone Tissue Regeneration, Stephen William Sawyer Dec 2018

Structurally Supported Cell-Laden Scaffolds For Bone Tissue Regeneration, Stephen William Sawyer

Dissertations - ALL

Due to challenges associated with current clinical techniques used to treat bone defects, there has been an increased focus on finding a tissue engineered solution. However, while great progress in this field has been achieved, researchers have yet to suitably combine the proper biological and structural environments needed to serve as a complete bone tissue substitute that is comparable to modern clinical solutions.

To achieve the goal of creating a model bone tissue substitute which could eventually serve as a viable therapy for bone trauma, be it caused by congenital medical conditions, age related diseases or high impact forces, three …


Mechanisms Of Calcium Phosphate Mineralization On Biological Interfaces And Their Engineering Applications, Doyoon Kim Dec 2018

Mechanisms Of Calcium Phosphate Mineralization On Biological Interfaces And Their Engineering Applications, Doyoon Kim

McKelvey School of Engineering Theses & Dissertations

All living organisms utilize phosphorus (P) as an essential component of their cell membranes, DNA and RNA, and adenosine triphosphate. Bones, in addition to bearing loads, play an important role in balancing P levels in our bodies. In bones, a network of collagen templates and calcium phosphate (CaP) nanocrystals builds hierarchical levels, from nano- to macroscale. Within this architecture, the thermodynamic properties of CaP minerals are influential. Despite the importance of nucleation, growth, and crystallization in collagen structures for tissue development, little kinetic study of these processes has been conducted due to the limited in situ techniques for monitoring these …


Design And Testing Of A Sheath Device To Secure Rotator Cuff Anchors In Osteoporotic Bone, Alissa Smith Dec 2018

Design And Testing Of A Sheath Device To Secure Rotator Cuff Anchors In Osteoporotic Bone, Alissa Smith

Masters Theses

A rotator cuff tear is a common injury that affects many elderly people. These tears vary in severity, with moderate to severe tears requiring surgery. In rotator cuff surgery, bone anchors are used to re-attach the supraspinatus tendon to the humerus. This surgery is difficult in many older patients because aging bones become osteoporotic, or soft, and thus inadequate for securing bone anchors. Studies confirm that osteoporotic bone is a contributing factor of implant failure. A finned sheath concept was designed, developed, and tested to ensure securement of the bone anchors during and after rotator cuff repair. The sheath interacts …


The Role Of Obesity And Dietary Fatty Acid Content In Regulating Humeral Bone And Cartilage Homeostasis, Lauren Votava Apr 2018

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 Apr 2018

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 Aug 2017

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 Jan 2017

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 …


Nanoindentation Properties Of Newly Formed Bone Surrounding Dental Implants Treated With E7-Modified Rbmp-2 Peptides, Ryan Doud Jan 2017

Nanoindentation Properties Of Newly Formed Bone Surrounding Dental Implants Treated With E7-Modified Rbmp-2 Peptides, Ryan Doud

All ETDs from UAB

Statement of Purpose: Use of titanium dental implants for treatment of partial or total edentulism has been well documented since the 1980s with consistent long term results. Osseointegration of these implants can be complicated by insufficient bone after healing of extraction sockets or systemic conditions such as osteoporosis or diabetes. Surface modifications, such as grit blasting (mechanical abrasion) or calcium phosphate (CaP) (chemical treatment) can improve healing time and bone quality around an implant. Our study combined a CaP coating with recombinant bone morphogenetic protein-2 (rBMP-2) mimetic peptide and the polyglutamate domain E7. We used nanoindentation to compare the elastic …


X-Ray Fluorescence For Quantification Of Lead And Strontium In Vivo, Aaron James Specht Aug 2016

X-Ray Fluorescence For Quantification Of Lead And Strontium In Vivo, Aaron James Specht

Open Access Dissertations

Lead (Pb) is a toxicant well known for its effects on almost every organ system in the body. Pb use in industry has declined since removal of Pb from gasoline, but many developing countries still have significant use of Pb. Exposure to Pb has been linked with diseases causing neurodegeneration and thus have lasting effects long after the initial exposure. Another metal, strontium (Sr), has been linked with bone disease in particular situations and shown to have uses in treating osteoporosis as a supplement. However, there are no studies of the effects of Sr using a meaningful biomarker. The most …


Densified Collagen-Fibril Biomaterials For Bone Tissue Engineering, Lauren E. Watkins Apr 2016

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 Jan 2016

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 Jan 2016

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 …


Shape Memory Polymers As 2d Substrates And 3d Scaffolds For The Study Of Cell Mechanobiology And Tissue Engineering, Richard Mcclary Baker Dec 2015

Shape Memory Polymers As 2d Substrates And 3d Scaffolds For The Study Of Cell Mechanobiology And Tissue Engineering, Richard Mcclary Baker

Dissertations - ALL

Tissue engineering is a promising, fast-growing field that combines cells, signals, and scaffolds to regenerate damaged tissues. To develop new, functional, engineered tissues, it is becoming increasingly important to understand how cell-material interactions affect the cell mechanobiological response. As a result, recent efforts have focused on developing complex synthetic materials that can mimic the dynamic in vivo cell environment. In this work, shape memory polymers (SMPs) were employed to develop dynamic 2D substrates and 3D scaffolds that undergo programmed changes in shape under cell compatible conditions. These substrates and scaffolds were applied in vitro and in vivo to demonstrate their …


Analysis Of Citrate Content In Bone Using High Performance Liquid Chromatography, Matthew Konstantin Pysh Dec 2015

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 …


The Design Of An Optimized Patient-Specific In Vivo Spinal Fusion Cage Using Additive Manufacturing, Gorman Donnelly Jun 2015

The Design Of An Optimized Patient-Specific In Vivo Spinal Fusion Cage Using Additive Manufacturing, Gorman Donnelly

Honors Theses

This project involved the design of an all-in-one patient-specific lumbar spinal fusion cage using Direct Metal Laser Sintering (DMLS) manufacturing. The cage is zero-profile and does not need the use of supplemental fixation. It was manufactured out of the titanium alloy Ti 6Al-4V using a DMLS rapid prototyping machine from a third party company. The endplates of the cage are patient-specific allowing for a larger surface contact area between the cage and the vertebral bodies than most cages on the market. This fosters a more successful fusion as well as decreases surgery time, effectively decreasing recovery time. Different porosity variations …


A Finite Element Analysis On The Viscoelasticity Of Postmenopausal Compact Bone Utilizing A Complex Collagen D-Spacing Model, Austin C. Cummings Jun 2015

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 May 2015

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 …


Synthesis And Characterization Of A Collagen Based Biodegradable Polymer Initiated By Hydroxyapatite Nanoparticle For Bone Regeneration, Didarul B. Bhuiyan Jan 2015

Synthesis And Characterization Of A Collagen Based Biodegradable Polymer Initiated By Hydroxyapatite Nanoparticle For Bone Regeneration, Didarul B. Bhuiyan

All ETDs from UAB

Synthetic bone graft biomaterials are considered as a potential alternative to the conventional use of bone grafts, due to their limitless supply and lack of disease transmission. Current synthetic bone graft materials generally lack the necessary combination of biological and mechanical properties for use as a bone graft substitute. Bone is a dynamic tissue that serves biological, chemical and mechanical purpose in the body and it is unlikely that a single component synthetic biomaterial can provide the appropriate combination of mechanical integrity and biological stimulation to replace bone. Multicomponent biomaterials need chemical bonding between the components to prevent phase separation …


A Local, Sustained Delivery System For Zoledronic Acid And Rankl-Inhibitory Antibody As A Potential Treatment For Metastatic Bone Disease, Rohith Jayaram Jan 2015

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 …


The Optimization Of Porosity And Pore Patterning For Patient-Specific Ti-6 Al-4v Femur Implants, Stephen Paolicelli Jun 2014

The Optimization Of Porosity And Pore Patterning For Patient-Specific Ti-6 Al-4v Femur Implants, Stephen Paolicelli

Honors Theses

Metastatic bone cancer often arises in the long bones of the body. Taking a patient specific approach by utilizing a customized implant is a superior method of treatment compared to today’s solutions, which often includes amputation. A titanium-alloy femur implant has been optimized by varying pore size, pore pattern, and porosity in order to maximize osseointegration. By maximizing osseointegration, the implant will remain firmly in place for a longer period of time because bone will grow throughout the implant, securing it. In addition, it is important for the bone to behave mechanically like bone. This requires the global elastic modulus …


Human Hair Keratin Protein, Hair Fibers And Hydroxyapatite (Ha) Composite Scaffold For Bone Tissue Regeneration, Samuel Siyum Jan 2014

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 Aug 2013

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 …