Browsing by Author "Haut Donahue, Tammy L., advisor"

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Open Access
Development of a hierarchical electrospun scaffold for ligament replacement
(Colorado State University. Libraries, 2018) Pauly, Hannah Marie, author; Haut Donahue, Tammy L., advisor; Easley, Jeremiah, committee member; Kelly, Daniel J., committee member; Palmer, Ross, committee member; Popat, Ketul C., committee member
The anterior cruciate ligament (ACL) is a dense collagenous structure that connects the femur to the tibia and is vital for joint stability. The ACL possesses complex time-dependent viscoelastic properties and functions primarily to prevent excessive translations and rotations of the tibia relative to the femur. It is estimated that 400,000 ACL tears occur in the United States annually and the monetary burden of these injuries and their subsequent treatment is approximately $1 billion annually. After injury allografts and autografts are commonly implanted to reconstruct the torn ACL in an attempt to restore joint stability, prevent pain, and limit damage to surrounding tissues. However surgical reconstructions fail to completely restore knee functionality or prevent additional injury and regardless of intervention technique radiographic osteoarthritis is present in 13% of patients 10 years after ACL rupture. Drawbacks to traditional treatments for ACL ruptures motivate the development of a synthetic ACL replacement. Tissue engineering is the use of a scaffold, cells, and signaling molecules to create a replacement for damaged tissue. The goal of this work is to develop a polymer scaffold that can be utilized as a replacement for the ACL. A tissue engineered ACL replacement should replicate the hierarchical structure of the native ACL, possess reasonable time zero mechanical properties, and promote the deposition of de novo collagenous tissue in vitro. Additionally, the scaffold should be implantable using standard surgical techniques and should maintain in situ tibiofemoral contact mechanics. Thus, four specific aims are proposed: 1) Fabricated and characterize an aligned 3-dimensional electrospun scaffold for ACL replacement. 2) Assess the in vitro behavior of ovine bone marrow-derived stems cells seeded on the scaffold in the presence of conjugated growth factor. 3) Evaluate the performance of the electrospun scaffold using uniaxial mechanical testing. 4) Assess the effect of the electrospun scaffold on ovine stifle joint contact mechanics. Development of a tissue engineered ACL replacement that mimics the structure and function of the native ACL would provide a novel treatment to improve outcomes of ACL injuries.
Open Access
Dynamic structural analysis of ramming in bighorn sheep
(Colorado State University. Libraries, 2015) Drake, Aaron Michael, author; Haut Donahue, Tammy L., advisor; Donahue, Seth W., advisor; Stansloski, Mitchell, committee member; Heyliger, Paul, committee member
Concussions are the most common traumatic brain injury and are caused by impulsive loads applied to the skull, resulting in relative motion of the brain within the brain cavity. Despite wearing helmets, athletes involved in full contact sports, such as football, are highly susceptible to concussive injuries. Short term symptoms of concussions include nausea, headache and confusion and there is evidence of more serious, long term effects from repeated concussions. Furthermore, the physical mechanisms of concussions are not well understood, making them difficult to diagnose and treat clinically. Male bighorn sheep sustain massive impact loads to the head during ramming, which is done as a means of determining hierarchy and gaining mating privileges. These large animals thrust themselves, horns first, at one another and collide violently, repeating this ritual for up to several hours until the subdominant male succumbs. After a collision, the animals are stunned momentarily but otherwise appear to suffer no ill effects, based on behavioral observations. This simple fact provided the motivation to examine the dynamic structural behavior of bighorn sheep horns and skulls. For reference, the average translational brain cavity accelerations observed during finite element model impact were found to be 111g (1091 m/s²) and impacts thought to be damaging to human brains occur at around 100g. A dynamic finite element impact model was produced using the geometry, obtained from a CT scan, of a mature male bighorn sheep’s skull and horns. Quantitative and qualitative results of the simulation were examined to determine mechanisms of energy dissipation and stress distribution during an idealized impact event. Video analysis of particularly forceful ramming sequences of wild bighorn sheep was carried out to estimate the dynamics involved with ramming. In order to investigate the relative contributions of the horn curl as well as the internal foamy bone architecture, three separate finite element models were produced. One model had one half of the horn length removed, another had the internal foam-like bone removed and these models were compared to the fully intact model to determine the structural contributions of these features during impact. Removing one half of the horn curl had the effect of increasing the peak brain cavity translational acceleration by 49%. Eliminating the internal foamy bone architecture resulted in a dramatic 442% increase in brain cavity rotational accelerations. The dynamic (vibrational) response of bighorn sheep horns and skulls was investigated using two, related methods: finite element modal analysis and experimental modal analysis. The finite element modal analysis revealed five dominant natural frequencies with values ranging from 118 to 309 Hz. Experimental modal analysis revealed several natural frequencies between 100 and 300 Hz, however, differentiating specific modes was difficult. For both vibrational analyses the dominant vibrational mode shape was side-to-side oscillations of the horn tip. This study hopes to promote and guide further research on the mechanisms of brain trauma prevention in bighorn sheep, with an emphasis on the structural and material characteristics of the horn and skull, to increase our understanding of, and ways to prevent traumatic brain injuries in humans.
Open Access
Engineering effective fibrocartilage replacement technologies using nanostructure-driven replication of soft tissue biomechanics in thermoplastic elastomer hydrogels
(Colorado State University. Libraries, 2018) Lewis, Jackson Tyler, author; Bailey, Travis S., advisor; Haut Donahue, Tammy L., advisor; James, Susan P., committee member; Popat, Ketul C., committee member; Li, Yan, committee member
Synthesis of hydrogel networks capable of accurately replicating the biomechanical demands of musculoskeletal soft tissues continues to present a formidable materials science challenge. Current systems are hampered by combinations of limited moduli at biomechanically relevant strains, inefficiencies driven by undesirable hysteresis and permanent fatigue, and recovery dynamics too slow to accommodate rapid cycling prominent in most biomechanical loading profiles. This dissertation presents a new paradigm in hydrogel design based on prefabrication of an efficient nanoscale network architecture using the melt-state self-assembly of amphiphilic block copolymers. Rigorous characterization and preliminary mechanical testing reveal that swelling of these preformed networks produce hydrogels with physiologically relevant moduli and water compositions, negligible hysteresis, sub-second elastic recovery rates, and unprecedented resistance to fatigue over hundreds of thousands of compressive cycles. By relying only on simple thermoplastic processing to form these nanostructured networks, the synthetic complexities common to most solution-based hydrogel fabrication strategies are completely avoided. Described within this dissertation are a range of efforts, broadly focused on refining synthetic and post-synthetic processing techniques to improve the modulus, surface hydrophilicity, fatigue resistance and cytocompatibility of these thermoplastic elastomer hydrogels, with the ultimate goal of producing a material viable as a meniscal replacement.
Open Access
Finite element analysis of skeletal muscle: a validated approach to modeling muscle force and intramuscular pressure
(Colorado State University. Libraries, 2017) Wheatley, Benjamin Brandt, author; Haut Donahue, Tammy L., advisor; Browning, Raymond C., committee member; Kaufman, Kenton R., committee member; Puttlitz, Christian M., committee member
Impaired muscle function can such as weakness is a reduction in muscle quality or quantity. Muscle weakness is debilitating conditions which can result from neuromuscular diseases and conditions such as multiple sclerosis, muscular dystrophy, stroke, injury, and aging. Impaired muscle function leads to disability, risk of injury, decreases in quality of life, and even death. Early disease detection, rehabilitation efforts, surgical techniques, and drug delivery can all be improved with the ability to identify muscle weakness by determining individual muscle force in vivo. Current clinical methods fail to measure individual muscle force as they are either inaccurate for individual muscle estimations (torque measurements) or are too invasive (buckle transducer insertion). Electromyography (EMG) is commonly used to diagnose improper muscle function, yet it is only a measurement of electrical activity. Thus, there is no minimally invasive clinical method which currently evaluates muscle force in vivo, which makes identifying and treating impaired muscle a challenge. Pressure of interstitial fluid within muscle (i.e. Intramuscular Pressure, IMP) is the direct result of active muscle contraction or passive stretch. A low profile pressure microsensor can be used to measure IMP and thus evaluate force of individual muscles in vivo. Accurate microsensor use however, is reliant upon developing a relationship between IMP and force, which is currently incomplete. Specifically, while force and IMP are correlated, the variability of IMP in vivo makes muscle force estimates from IMP measurements a challenge. Additionally, the distribution of IMP throughout muscle is variable and poorly understood. The goal of this work is to develop a computational model which can be used to better understand the behavior of intramuscular pressure. However, a lack of mechanical experimental analysis of skeletal muscle makes developing a robust model a challenge. Thus, two specific aims are proposed: 1) Experimentally investigate the passive properties of skeletal muscle and identify proper modeling assumptions to make in developing a constitutive approach. 2) Develop and implement a finite element approach for skeletal muscle which is capable of simulating muscle force and intramuscular pressure under passive stretch and active contraction conditions. Implementation of this model will provide insight into the potential causes of variability of intramuscular pressure measurements in vivo and future clinical approaches.
Open Access
From meniscus to bone: structure and function of human meniscal entheses and deleterious effects of osteoarthritis
(Colorado State University. Libraries, 2013) Abraham, Adam Christopher, author; Haut Donahue, Tammy L., advisor; Kaufman, Kenton R., committee member; Puttlitz, Christian M., committee member; Popat, Ketul C., committee member; Goodrich, Laurie R., committee member
Knee osteoarthritis plagues millions of people in the U.S. alone, yet the mechanisms of initialization are not well understood. Recent work suggests that there are a myriad of potential disease inducing routes that may give rise to this debilitating condition. Understanding and elucidating the potential pathways leading to osteoarthritis may result in novel methods of prevention and/or treatment. Human meniscus are C-shaped fibrocartilaginous structures contained within the diathroidal knee joint, the primary function of which are to provide support and lubrication between the femur and the tibia. Each knee incorporates two menisci, lateral and medial, affixed at the anterior and posterior attachment sites to the tibial plateau. Meniscal attachments, or entheses, are unique graded tissue interfaces comprised of four distinct zones that diffuse longitudinal loads transmitted via hoop stresses of collagen fibrils in the meniscal body. The attachments must remain firmly rooted to the tibial plateau to effectively attenuate joint loads. If the attachments become structurally compromised, either through direct or indirect means, excessive transverse meniscal translation results. Such joint extrusion of the meniscal body is a known precursor to developing osteoarthritis. To date there have been no investigations of integrity of meniscal attachments in the aged arthritic knee. A proposed treatment modality for meniscus degeneration is engineered replacements which focus solely on the meniscal body, disregarding the specialized tissue interface. However, the efficacy of these replacements likely remains dependent on restoring the meniscus to bone transition. Previous literature has shown that each meniscal attachment is biochemically and mechanically unique and thus should be independently examined. Therefore, the overall goal of this work is to examine the loading environment of each attachment in both a healthy and injured knee, as well as characterize the structure-function relationship. This knowledge can then be utilized to develop novel preventative strategies in order to deter the onset of osteoarthritis, thereby reducing the burden on individuals as they age. Therefore, the goal of this work was to: • Determine the transverse mechanical properties of the attachment sites and couple with current literature to aid in numerical modeling • Determine the native loading environment for each attachment under physiological and pathlogical loading conditions • Examine the structure and function of the native attachment sites • Examine the deleterious effects of osteoarthritis on the attachment sites.
Open Access
Meniscal root tears and repairs
(Colorado State University. Libraries, 2018) Steineman, Brett Daniel, author; Haut Donahue, Tammy L., advisor; LaPrade, Robert F., committee member; Goodrich, Laurie R., committee member; Heyliger, Paul R., committee member
Meniscal root tears are defined as radial tears of the meniscal insertions and lead to an inability for the menisci to transmit compressive loads into circumferential hoop stresses. These are common among the posterior meniscal insertions due to acute or chronic conditions. Anterior root tears have also been shown to occur from iatrogenic injury during anterior cruciate ligament reconstructions; however, the relationship between anterior insertions and the anterior cruciate ligament are understudied. Root tears of the posterior insertions lead to measurable osteoarthritis within a year if left untreated. Despite this, changes to tissue characteristics due to anterior root tears are unknown. If untreated anterior roots result in tissue degeneration, then it is important for both anterior and posterior root tears to be repaired to prevent, or at least delay, the onset of osteoarthritis. Meniscal root repair techniques have been developed to prevent joint degeneration following meniscal root tears; however, clinical studies of root repairs show that meniscal extrusion and joint degeneration are not completely prevented. This limited repair success may be due to inaccurate placement of repairs during surgery or from repair loosening postoperatively as early as during rehabilitation. The goals of this work are to better understand anterior root tears and to investigate potential causes for insufficient meniscal root repairs. Thus, the aims are to: 1) Quantify the overlap between the anterior cruciate ligament and the anterolateral meniscal insertion in the coronal and sagittal planes. 2) Assess early in vivo degeneration after untreated anterior meniscal root tears. 3) Determine the extent of repair loosening and recovery due to short-term rehabilitation. 4) Develop finite element knee models to determine the effect of repair placement and loosening on knee mechanics. The completion of this project will improve clinical practice and basic scientific knowledge of current issues facing meniscal root tears and repairs.