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Browsing by Author "Donahue, Seth, committee member"

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    Constitutive modeling of the biaxial mechanics of brain white matter
    (Colorado State University. Libraries, 2016) Labus, Kevin M., author; Puttlitz, Christian M., advisor; Donahue, Seth, committee member; Heyliger, Paul, committee member; James, Susan, committee member
    It is important to characterize the mechanical behavior of brain tissue to aid in the computational models used for simulated neurosurgery. Due to its anisotropy, it is of particular interest to develop constitutive models of white matter based on experimental data in order to define the material properties in computational models. White matter has been shown to exhibit anisotropic, hyperelastic, and viscoelastic properties. The majority of studies have focused on the shear or compressive properties, while few have tested the tensile properties of the brain. Brain tissue has not previously been tested in a multi-axial loading state, even though in vivo brain tissue is in a constant multi-axial stress state due to fluid pressure, and data from uniaxial experiments do not sufficiently describe multi-axial stresses. The main objective of this project was to characterize the biaxial tensile behavior of brain white matter via experimentation and constitutive modeling. A biaxial experiment was developed specifically for testing brain tissue. Experiments were performed at a quasi-static loading rate, and an Ogden anisotropic hyperelastic model was derived to fit the data. A structural analysis was performed on biaxially tested specimens to relate the structure to the mechanical behavior. The axonal orientation and distribution were measured via histology, and the axon area fraction was measured via transmission electron microscopy. The measured structural parameters were incorporated into the constitutive model. A probabilistic analysis was performed to compare the uncertainty in the stress predictions between models with and without structural parameters. Finally, dynamic biaxial experiments were performed to characterize the anisotropic viscoelastic properties of white matter. Biaxial stress-relaxation experiments were conducted to determine the appropriate form of a viscoelastic model. It was found that the data were accurately modeled by a quasi-linear viscoelastic formulation with an isotropic reduced relaxation tensor and an instantaneous elastic stress defined by an anisotropic Ogden model. Model fits to the stress-relaxation experiments were able to accurately predict the results of dynamic cyclic experiments. The resulting constitutive models from this project build upon previous models of brain white matter mechanics to include biaxial interactions and structural relations, thus improving computational model predictions.
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    Do mesenchymal stromal cells abrogate the immune response in massive cortical allograft recipients?
    (Colorado State University. Libraries, 2015) McNamara, Kaitlyn Louise, author; Ehrhart, Nicole, advisor; Dow, Steven, advisor; Donahue, Seth, committee member; Duncan, Colleen, committee member; Palmer, Ross, committee member; Page, Rodney, committee member
    OBJECTIVE: To evaluate the humoral and cellular immune response against bone associated antigens when delivered in a vaccine, and to evaluate the immunomodulation on the aforementioned immune response with the addition of adipose-derived mesenchymal stromal cells (AD-MSCs). ANIMALS: 68 C57BL/6 mice PROCEDURES: Femur fragments harvested from Balb/C or C57BL/6 mice were resuspended in PBS and cationic liposomal DNA complexes (CLDC) to create an allograft or autograft vaccine, respectively. A positive control vaccine was created utilizing bovine alkaline phosphatase (ALP) resuspended in PBS and CLDC. Twenty C57BL/6 mice were divided into four treatment groups: non-vaccinated (n=5), ALP vaccine recipients (n=5), allograft bone vaccine recipients (n=5), or autograft bone vaccine recipients (n=5). Forty-eight C57BL/6 mice were divided into the same 4 vaccine treatment groups (n=16), and received either intravenous AD-MSCs (n=8) or a subcutaneous injection of AD-MSCs (n=8). All mice received an initial vaccine on Day 1 and a booster vaccine on Day 7, followed by euthanasia on Day 21. Blood was collected on Day 1 and Day 7 just prior to vaccination, and on Day 21 just prior to euthanasia. Serum was subjected to an antibody detection ELISA to evaluate the humoral response. Spleens were collected and flow cytometry was used to evaluate T cell proliferation as an indicator of the cellular immune response. RESULTS: The bone vaccines did no elicit a detectable humoral immune response to the total bone antigen vaccine used in this model. The addition of AD-MSCs had no effect on the lack of a detectable humoral immune response. The T cell response towards a bone antigen was dampened in mice previously vaccinated with a bone vaccine. This effect was most pronounced when looking at the T cell response towards an allograft bone antigen in mice previously vaccinated with an allograft bone vaccine, particularly with the addition of AD-MSCs. CONCLUSIONS AND CLINICAL RELEVANCE: The bone vaccine model used in this study allowed evaluation of the humoral and cellular immune response towards bone associated antigens. The model suggests that recipients of an allograft bone vaccine will dampen the T cell proliferation seen upon second exposure to the bone antigens. This model could be used in future vaccine studies looking at the effect of vaccinating mice with a bone vaccine prior to undergoing a limb-salvage procedure. If efficacious, the bone vaccine model may provide a new treatment option for decreasing the risk of transplant rejection following massive limb reconstruction.
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    Evaluation of meniscal changes in two models of knee osteoarthritis: traumatic loading and modified transection
    (Colorado State University. Libraries, 2013) Fischenich, Kristine Marie, author; Donahue, Tammy Haut, advisor; Donahue, Seth, committee member; Goodrich, Laurie, committee member
    Osteoarthritis (OA) is a debilitating joint disease characterized by the erosion of articular cartilage on the ends of long bones, causing painful bone on bone contact. OA can affect any joint but is commonly seen in the knee and is a major cause of disability. Normally thought of as a degenerative disease, the early onset of OA can be triggered by a number of factors including injury to the joint. With the number of younger athletes increasing as well as the incidence of knee injury increasing it is important to understand the development and progression of post traumatic OA (PTOA). Only then can measures be taken to prevent, or slow the progression. The most common method to study PTOA of the knee involves using an animal model where the anterior cruciate ligament is transected (ACLT). The ACLT model fails to account for a number of factors that are commonly seen in clinical cases. The compressive forces experienced by the joint as well as damage to other joint structures are not accounted for in the tradition ACLT model. Furthermore, despite the well documented role of the meniscus in joint stability and joint kinematics other tissues such as the articular cartilage and subchondral bone have received more attention. PTOA is a "whole organ" disease where damage to one structure influences other structures, and in order to fully understand the progression the entire joint must be studied. There is a lack of knowledge as to how the meniscus is both affected and influences the development of OA. To better understand its role there have been two PTOA models developed for this study. The first is a modified ACLT model (mACLT), where meniscal damage is surgically induced at the time of ACL transection. The second model is a traumatic tibiofemoral compressive impact model (ACLF) where the ACL is ruptured due to a blunt force trauma to the joint. The objective of this thesis was to monitor meniscal changes twelve weeks following impact for both the mACLT and ACLF model. Meniscal damage was monitored over time with the use of magnetic resonance imaging MRI. At dissection gross morphology was graded and compared to the acute and chronic MRI notes. Each meniscus was then sectioned into regions and mechanically tested. Indentation relaxation testing allowed for the instantaneous as well as equilibrium elastic moduli to be calculated. Following mechanical testing meniscal tissue was fixed and stained for glycosaminoglycan (GAG) content. Using semi qualitative analysis, the GAG intensity and coverage was analyzed. Acute and chronic damage, elastic moduli, and GAG content from the injured limbs was then compared to the contralateral controls.