京都大学 / 新制・課程博士 / 博士(医学) / 甲第23604号 / 医博第4791号 / 新制||医||1055(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 戸口田 淳也, 教授 河本 宏, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Energy densities (ED, mJ/mm3) quantify mechanical work imposed on articular cartilages during function. This cross-sectional study examined differences in temporomandibular joint (TMJ) ED during asymmetric versus symmetric jaw closing in healthy females versus males. ED component variables were tested for differences between and within sexes for two types of jaw closing. Seventeen female and 17 male subjects gave informed consent to participate. Diagnostic criteria for temporomandibular disorders and images (magnetic resonance (MR), computed tomography) were used to confirm healthy TMJ status. Numerical modelling predicted TMJ loads (Fnormal) consequent to unilateral canine biting. Dynamic stereometry combined MR imaging and jaw-tracking data to measure ED component variables during 10 trials of each type of jaw closing in each subject's TMJs. These data were then used to calculate TMJ ED during jaw closing asymmetrically and symmetrically. Paired and Student's t tests assessed ED between jaw closing movements and sexes, respectively. Multivariate data analyses assessed ED component variable differences between jaw closing movements and sexes (α = 0.05). Contralateral TMJ ED were 3.6-fold and significantly larger (P <.0001) during asymmetric versus symmetric jaw closing, due to significantly larger (P ≤.001) distances of TMJ stress-field translation in asymmetric versus symmetric movement. During asymmetric jaw closing, contralateral TMJ ED were twofold and significantly larger (P =.036) in females versus males, due to 1.5-fold and significantly smaller (P ≤.010) TMJ disc cartilage volumes under stress fields in females versus males. These results suggest that in healthy individuals, asymmetric compared to symmetric jaw closure in females compared to males has higher TMJ mechanical fatigue liabilities.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第19180号 / 人健博第28号 / 新制||人健||3(附属図書館) / 32172 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 高桑 徹也, 教授 市橋 則明, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13068号 / 論医博第2123号 / 新制||医||1019(附属図書館) / 33219 / 京都大学大学院医学研究科医学専攻 / (主査)教授 妻木 範行, 教授 開 祐司, 教授 戸口田 淳也 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第20297号 / 人健博第45号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 坪山 直生, 教授 山田 重人, 教授 妻木 範行 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

The objective of this study was to evaluate the effects of sex, loading rate, and age on the compressive and tensile material properties of human costal cartilage over a wide range of subject ages and sexes. Cylindrical compression samples and dog-bone shaped tension samples were tested to failure on a material testing system using target strain rates of 0.005 strain/s and 0.5 strain/s. Compression data were obtained from forty (n = 40) subjects (M = 26, F = 14) ranging in age from 11 – 69 years (Avg. = 39.1 ± 18.2 yrs.), and matched loading rate data were obtained for thirty-four (n = 34) samples. Tension data were obtained from forty-one (n = 41) subjects (M = 30, F = 11) ranging in age from 10 – 59 years (Avg. = 32.9 ± 14.9 yrs.), and matched loading rate data were obtained for seventeen (n = 17) samples. For both compression and tension, load and sample deflection data were collected and used to calculate stress and strain. For the compression data, the toe region was fit using a second-order polynomial, and the toe transition stress, toe transition strain, second-order polynomial coefficient A, and second-order polynomial coefficient B were calculated. In addition, the elastic modulus, ultimate stress, ultimate strain, and strain energy density (SED) were also calculated for each test. For the tension data, only the elastic modulus, ultimate stress, ultimate strain, and SED were calculated for each test. There were no effects of sex on the material properties for either method of loading or strain rate. Therefore, male and female data were combined for the age and loading rate analyses. For compression, toe transition stress, toe transition strain, A, elastic modulus, ultimate stress, and SED were all found to be significantly higher at 0.5 strain/s compared to 0.005 strain/s. For tension, no material properties were found to differ with respect to loading rate. Regarding the effects of age, toe transition stress, toe transition strain, A, B, ultimate stress, ultimate strain and SED were found to significantly decrease with advancing age for the 0.005 strain/s compression data. At 0.5 strain/s, toe transition stress, toe transition strain, elastic modulus, ultimate stress, ultimate strain, and SED all significantly decreased with advancing age. For tension, ultimate stress, ultimate strain, and SED were found to significantly decrease with advancing age at 0.005 strain/s and 0.5 strain/s. Comparing the two loading modes, the ultimate stress, elastic modulus, and SED were significantly higher in compression than in tension. For the compression samples, sample density and percent calcification were also obtained for each sample using physical measurements and micro-CT scans, respectively. However, since there were only a few samples with large calcifications, no meaningful trends were found. This is the first study of its kind to analyze the effects of sex, loading rate, and age on both the compressive and tensile material properties on human costal cartilage from such a wide range of subject ages. The results from this study can be used to develop more accurate finite element models of the human body, which will allow researchers to better evaluate human occupant response and injury risk in motor vehicle collisions for both young and old individuals. / Master of Science / Serious thorax injuries are often observed in motor vehicle collisions. Although a considerable amount of research has investigated the material and structural properties of rib cortical bone and whole rib sections, only a limited number of studies have focused on characterizing the material properties of costal cartilage, which comprises a substantial portion of the anterior region of the thorax. The studies that do exist include small subject pools and/or are limited to sub-failure indentation tests. Indentation tests are limited to low deflections and focal loading and are unable to obtain the failure material properties of costal cartilage. Therefore, the purpose of this study was to quantify the compressive and tensile material properties of human costal cartilage at two loading rates for a wide range of subject demographics. These properties were then evaluated with respect to sex, loading rate, and age. Cylindrical compression samples and dog-bone shaped tension samples were tested to failure on a material testing system at target strain rates of 0.005 strain/s and 0.5 strain/s. Compression data were obtained from forty (n = 40) subjects ranging in age from 11 – 69 years, and tension data were obtained from twenty-eight (n = 28) subjects ranging in age from 10 – 59 years. For both compression and tension, load and sample deflection data were collected and used to calculate stress and strain. For the compression data, the magnitude and shape of the initial loading region (i.e., the toe region), elastic modulus, ultimate stress, ultimate strain, and strain energy density (SED) were quantified for each test. For the tension data, the elastic modulus, ultimate stress, ultimate strain, and SED were calculated for each test. There were no significant effects of sex on the material properties for either method of loading or strain rate. Therefore, male and female data were combined for the age and loading rate analyses. For compression, the toe region transition point (i.e., stress and strain), toe region shape coefficient A, elastic modulus, ultimate stress, and SED were all found to be significantly higher at 0.5 strain/s compared to 0.005 strain/s. For tension, no material properties were found to differ with respect to loading rate. Regarding the effects of age, toe region transition point (i.e., stress and strain), toe region shape coefficients A and B, ultimate stress, ultimate strain, and SED were found to significantly decrease with advancing age for the 0.005 strain/s compression data. For the 0.5 strain/s compression data, toe transition stress, toe transition strain, elastic modulus, ultimate stress, ultimate strain, and SED all significantly decreased with age. For tension, ultimate stress, ultimate strain, and SED were found to significantly decrease with advancing age at 0.005 strain/s and 0.5 strain/s. The ultimate stress, elastic modulus, and SED were higher in compression than in tension. Overall, this is the first study to evaluate the effects of sex, loading rate and age on the compressive and tensile material properties of human costal cartilage from a wide range of ages. These data can be used to assess differences in the response and tolerance of the human rib cage for occupants of various age in motor vehicle collisions.

Articular cartilage is a smooth, white connective tissue that covers and protects the ends of long bones to allow for a smooth, frictionless surface on which to glide for easy movement. Once the tissue is damaged, articular cartilage lacks a direct blood supply, which results in a limited ability to repair itself. This study explores the effect of the growth factor BMP-13 on the chondroinduction of primary human bone marrow-derived mesenchymal stem cells. The results demonstrate the limited ability of BMP-13 to exert a strong chondroinductive effect on human bone marrow-derived MSCs. However, the results do indicate that BMP-13 has the ability to sustain chondroinduction to a certain extent for up to 18 days following initiation by 3 days of exposure to TGF-β3. Results are encouraging for future work that involves growth factor influence on MSCs in articular cartilage tissue engineering.

An estimated 27 million Americans suffer from osteoarthritis (OA). Symptomatic OA is often treated with total knee replacement, a procedure which is expected to increase in number by 673% from 2005 to 2030, and costs to perform total knee replacement surgeries exceeded $11 billion in 2005. Subject-specific modeling and finite element (FE) predictions are state-of-the-art computational methods for anatomically accurate predictions of joint tissue loads in surgical-planning and rehabilitation. Knee joint FE models have been used to predict in-vivo joint kinematics, loads, stresses and strains, and joint contact area and pressure. Abnormal cartilage contact pressure is considered a risk factor for incidence and progression of OA. For this study, three subject-specific tibiofemoral knee FE models containing accurate geometry were developed from magnetic resonance images (MRIs). Linear (LIN), Neo-Hookean (NH), and poroelastic (PE) cartilage material models were implemented in each FE model for each subject under three loading cases to compare cartilage contact pressure predictions at each load case. An additional objective was to compare FE predictions of cartilage contact pressure for LIN, NH, and PE material models with experimental measurements of cartilage contact pressure. Because past studies on FE predictions of cartilage contact pressure using different material models and material property values have found differences in cartilage contact pressure, it was hypothesized that different FE predictions of cartilage contact pressure using LIN, NH, and PE material models for three subjects at three different loading cases would find statistically significant differences in cartilage contact pressure between the material models. It was further hypothesized that FE predictions of cartilage contact pressure for the PE cartilage material model would be statistically similar to experimental data, while the LIN and NH cartilage material models would be significantly different for all three loading cases. This study found FE and experimental measurements of cartilage contact pressure only showed significant statistical differences for LIN, NH, and PE predictions in the medial compartment at 1000N applied at 30 degrees, and for the PE prediction in the medial compartment at 500N applied at 0 degrees. FE predictions of cartilage contact pressure using the PE cartilage material model were considered less similar to experimental data than the LIN and NH cartilage material models. This is the first study to use LIN, NH, and PE material models to examine knee cartilage contact pressure predictions using FE methods for multiple subjects and multiple load cases. The results demonstrated that future subject specific knee joint FE studies would be advised to select LIN and NH cartilage material models for the purpose of making FE predictions of cartilage contact pressure.

Articular Cartilage (AC) is the main load carrying material in synovial joints {Hamerman, 1962} and degeneration of AC can cause pain in the form of arthritis. Current work is centered on the method of replacing damaged cartilage inside the body (in vivo) with tissue engineered outside the body (ex vivo) {Temenoff, 2000}. In order to engineer tissue ex vivo similar to the native tissue in structure and function there must be a comprehensive understanding of the mechanical properties of AC. This work focuses on the study of glycosaminoglycans (GAGs), a molecule known to be primarily responsible for the compressive stiffness of AC, using molecular dynamics methods. First, a single chain simulation is run to establish a chain length to use for the rest of the study. Then two more simulations are run that mimic a possible physical scenario for changing GAG density. The first is a five chain simulation that mimics the situation where GAG chains are compressed and pushed together. Pressure and density relations are generated and compared to the micro-structural level Donnan model {Maroudas, 1979} and Poisson-Boltzmann unit cell (PB) model {Marcus, 1955}. The last simulation imitates the scenario of one GAG chain sliding between two adjacent GAG chains. The work to pull the central chain through the adjacent chains is calculated and plotted at different chain spacing. A 20 disaccharide-unit long chain is found to be the most stable chain length, but for the purpose of saving computational time without a large loss in stability a 10 unit chain is used for the rest of the simulations. The pressure-density relations found from the five chain simulation are of the same magnitude as the micro-structural level models. Observations made based on the graphical playback of the pulling simulation give insight into the importance of ion interaction with the GAG chains. It was found to take more work to pull the chain with more open space around because of the binding nature of the ions coming between the chains. The tighter spaced chains allowed fewer ions to fit between chains creating less binding force, therefore taking less work to pull. This work can be scaled up to the next level using coarse-graining methods which will be more comparable to experimental work, possibly leading to results that will help characterize AC for better implementation of engineered tissue.

Articular cartilage degeneration, called osteoarthritis, in the hip joint is a serious condition that affects millions of individuals yearly, with limited clinical solutions available to prevent or slow progression of damage. Additionally, the effects of high-risk factors (e.g. obesity, soft and hard tissue injuries, abnormal joint alignment, amputations) on the progression of osteoarthritis are not fully understood. Therefore, the objective of this thesis is to generate a finite element model for predicting osteochondral tissue stress and strain in the human hip joint during gait, with a future goal of using this model in clinically relevant studies aimed at prevention, treatment, and rehabilitation of OC injuries. A subject specific finite element model (FEM) was developed from computerized tomography images, using rigid bones and linear elastic isotropic material properties for cartilage as a first step in model development. Peak contact pressures of 8.0 to 10.6 MPa and contact areas of 576 to 1010 mm2 were predicted by this FEM during the stance phase of gait. This model was validated with in vitro measurements and found to be in good agreement with experimentally measured contact pressures, and fair agreement with measured contact areas.