Thesis (Ph. D.)--Mechanical Engineering, Georgia Institute of Technology, 2006. / Dr. Marc E. Levenston, Committee Chair ; Dr. Lawrence J. Bonassar, Committee Member ; Dr. Robert E. Guldberg, Committee Member ; Dr. William J. Koros, Committee Member ; Dr. Christopher S. Lynch, Committee Member.

abstract: The flow of liquid PDMS (10:1 v/v base to cross-linker ratio) in open, rectangular silicon micro channels, with and without a hexa-methyl-di-silazane (HMDS) or poly-tetra-fluoro-ethylene (PTFE) (120 nm) coat, was studied. Photolithographic patterning and etching of silicon wafers was used to create micro channels with a range of widths (5-50 μm) and depths (5-20 μm). The experimental PDMS flow rates were compared to an analytical model based on the work of Lucas and Washburn. The experimental flow rates closely matched the predicted flow rates for channels with an aspect ratio (width to depth), p, between one and two. Flow rates in channels with p less than one were higher than predicted whereas the opposite was true for channels with p greater than two. The divergence between the experimental and predicted flow rates steadily increased with increasing p. These findings are rationalized in terms of the effect of channel dimensions on the front and top meniscus morphology and the possible deviation from the no-slip condition at the channel walls at high shear rates. In addition, a preliminary experimental setup for calibration tests on ultrasensitive PDMS cantilever beams is reported. One loading and unloading cycle is completed on a microcantilever PDMS beam (theoretical stiffness 0.5 pN/ µm). Beam deflections are actuated by adjusting the buoyancy force on the beam, which is submerged in water, by the addition of heat. The expected loading and unloading curve is produced, albeit with significant noise. The experimental results indicate that the beam stiffness is a factor of six larger than predicted theoretically. One probable explanation is that the beam geometry may change when it is removed from the channel after curing, making assumptions about the beam geometry used in the theoretical analysis inaccurate. This theory is bolstered by experimental data discussed in the report. Other sources of error which could partially contribute to the divergent results are discussed. Improvements to the experimental setup for future work are suggested. / Dissertation/Thesis / Masters Thesis Mechanical Engineering 2014

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22440号 / 工博第4701号 / 新制||工||1734(附属図書館) / 京都大学大学院工学研究科原子核工学専攻 / (主査)教授 横峯 健彦, 教授 佐々木 隆之, 教授 鈴木 基史 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Little research has been done to validate the biomechanical principles of tibial tuberosity advancement (TTA) throughout stance. The present study evaluates the effects of TTA on kinematics of the cranial cruciate (CrCL) deficient stifle during early, middle, and late stance. Cadaveric pelvic limbs were evaluated for the effects of TTA on kinematics under a load equivalent to 30% bodyweight and under the following treatment conditions: intact CrCL, CrCL deficient, TTA-treated, and TTA treated + meniscal release. Electromagnetic tracking sensors were used to determine tibial subluxation and rotation relative to the femur. Transection of the CrCL resulted in significant cranial tibial subluxation during early, middle, and late stance and significant internal rotation during early and middle stance. TTA normalized tibial subluxation in early, middle, and late stance but was unsuccessful in normalizing axial rotation in middle stance. Meniscal release had no effect on cranial/caudal or rotational displacement when performed following TTA.

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In der vorliegenden Arbeit konnten erstmals der TGF-β-Signalweg und dessen Smad- Signalmoleküle innerhalb der MPCs nachgewiesen werden. Dieser Nachweis erfolgte sowohl auf zellulärer und Gewebeebene als auch auf Gen- und Proteinebene. Zusätzlich konnte auf Gen- und Proteinebene gezeigt werden, dass die Signalmoleküle Smad2, Smad3 und Smad4 in MPCs aus gering erkranktem Meniskusgewebe eine vermehrte Expression aufweisen im Vergleich zu den MPCs aus hochgradig erkranktem Meniskusgewebe. Diese Erkenntnis weist auf eine mögliche protektive Funktion des TGF- β-Signalwegs während degenerativer Prozesse im Meniskusgewebe hin. Um die Effekte des TGF-β-Signalwegs und dessen Smad-Signalmoleküle genauer zu verstehen und besser beschreiben zu können, wurde eine Überexpression der Smad-Signalmoleküle innerhalb von MPCs durchgeführt und die Auswirkungen dieser auf die Kollagen I- und Kollagen II-Synthese genauer beleuchtet. Infolgedessen konnte sowohl eine vermehrte Kollagen I-Synthese als auch eine vermehrte Kollagen II-Synthese festgestellt werden. Dies bestätigt die Annahme, dass dem TGF-β-Signalweg und dessen Smad-Signalmolekülen eine zentrale, protektive Funktion während der Meniskusdegeneration zukommt. Durch die vermehrte Synthese von Matrixkomponenten wird den Degenerationsprozessen innerhalb des Meniskusgewebes entgegengewirkt. Ein nicht degenerierter bzw. ein regenerierter Meniskus besitzt eine biomechanische Schutzfunktion für das Kniegelenk und wirkt somit einer Kniegelenkarthrose entgegen. In Zukunft könnte der TGF-β-Signalweg  einen möglichen Ansatzpunkt für therapeutische Behandlungen bei Meniskusläsionen darstellen. Da Meniskusdefekte häufig direkt mit einer Osteoarthrose im Kniegelenk assoziiert sind, spielt die durch den TGF-β-Signalweg induzierte Regeneration von Meniskusgewebe auch in der Prävention der Osteoarthrose eine zentrale Rolle.

An evaporating meniscus formed by a wetting °uid in a heated capillary slot with capillary driven °flow is numerically and experimentally investigated at the microscale and pore scale. In the microscale analysis, the contact line region of an extended evaporating thin ¯lm meniscus is numerically investigated to study the influence of °uid properties on the heat transfer. The governing equations to describe the fluid °flow, heat and mass transfer phenomena in an evaporating extended meniscus are grouped uniquely as function of °uid dependent parameters, namely the interline heat flow number and heat pipe ¯figure of merit. A physical interpretation of these parameters is presented. Numerical experiments conducted with different working °fluids show that a °uid with a high interline heat °flow parameter and heat pipe ¯figure of merit also has a high cumulative heat transfer in the micro region encompassing the evaporating thin ¯lm. In the pore scale analysis, the evaporation from a pentane meniscus in a heated capillary slot is experimentally and numerically investigated to study how the wetting characteristics are influenced with heat input. In the experimental investigation, a test set up is fabricated with a heated glass capillary slot that is partially immersed in a constant temperature bath with constant °uid level. A novel aspect of this experiment is that both the wicking height and steady state evaporation mass flow rate are measured simultaneously. Based on a macroscopic force balance, the apparent contact angle of the evaporating meniscus is experimentally estimated from the wicking height and mass flow rate. This is compared with the results obtained using evaporating thin ¯lm theory. The experimentally estimated contact angle is higher than that obtained from the thin ¯lm model but both experiment and theory show similar trends. In the numerical study, a ¯finite volume numerical model of an evaporating meniscus in a heated capillary slot (simulating the above experimental condition) is developed for predicting the wicking height and mass flow rate. This model includes: (i) one-dimensional heat transfer and °uid °flow in the liquid and vapour regions of the capillary slot, (ii) one{dimensional evaporating thin ¯lm model for the meniscus region, and (iii) two-dimensional conduction heat transfer in the capillary wall. Correlations obtained from the evaporating thin{¯lm theory in terms of cumulative heat transfer and apparent contact angle are applied to the pore level problem. The problem is solved iteratively between the micro and pore scales till convergence is achieved. The wicking height is influenced by the change in apparent contact angle and the pressure drops to flow of liquid and vapor in the capillary slot that is a function of evaporation mass °ow rate. Heat input to the capillary slot increases both the contact angle in the evaporating meniscus and the frictional pressure drops in the liquid and vapor regions. In the present study, the influence of increased contact angle is more significant and the liquid and vapor pressure drops are negligible. The trends in the wicking height, mass flow rate and conductance are similar to the experimental data. The proposed numerical approach using correlations from thin ¯lm theory to link the micro and macro scales yields results that are consistent with experimental data. The results show that the change in contact angle can degrade the ability of the liquid to wet the pore and hence result in a lower heat transfer coefficident.

Knee osteoarthritis (OA) is the commonest form of lower limb OA with a lifetime risk of over 40%. It is a disease characterised by symptoms such as pain and loss of function. In addition there are typical structural features on both radiographs and MRI. Knee OA represents a spectrum of disease, ranging from early preclinical cartilage change to established full thickness disease. Anteromedial knee OA is a particular phenotype of knee OA where disease is confined to the medial compartment. Whilst end stage arthritis is treated reliably with joint arthroplasty, those with early stage disease are treated with a variety of non- surgical interventions with varying success. This thesis is concerned with understanding the disease of patients that have early radiographic changes but symptoms not controlled by conservative measures. Up to 150 of these patients a year present to the Nuffield Orthopaedic Centre, Oxford. They have been described as being in the “Treatment Gap”. A series of validation studies were performed to determine the optimal method for diagnosing cartilage defects within the knee. The three commonest diagnostic methods were examined for their validity. Arthroscopic assessments of cartilage lesions demonstrated a moderate level of intra and inter observer reliability. In contrast, radiographs and MRI demonstrated high levels of reliability. When using MRI as a criterion standard, both radiographs and arthroscopic assessment were found to have poor accuracy. Based on the work in this thesis a formal definition of the cartilage changes exhibited in early knee OA was proposed. A cross sectional cohort of 100 patients with the symptoms and radiological features of early knee OA were identified. Their pain and function profile was compared to two comparison groups of patients at the end stage of knee OA (defined by the need for partial or total arthroplasty). In up to 78% of individual cases those with early OA had pain and function profiles as bad as those with end stage disease. The cross sectional symptoms of early knee OA demonstrate a marked discordance with their mild radiographic changes. The same cohort was extended to 125 patients. They were followed over one year with monthly PROM assessments to determine how symptoms change over time. 43% of patients experience a clinical improvement over 12 months, 31% experience a clinical deterioration and 26% remain unchanged. The range in OKS variation over 12 months was on average 12 points, with clinically relevant variation occurring on 45% of monthly measurements. Patients with early knee OA can expect to experience considerable variation in their symptoms over 12 months and this must be considered when planning interventions. A number of patients with early knee OA were noticed to demonstrate medial meniscal extrusion. Using data from the Osteo Arthritis Initiative (OAI) a nested case control study was designed to determine how the presence of meniscal extrusion in an otherwise normal knee affects the risk of developing knee OA over the next 48 months. This demonstrated an Odds Ratio of 3.5, suggesting that meniscal extrusion is a considerable risk factor for the development of OA. The presence of a knee injury or operative intervention to the index meniscus was shown to increase this risk. Many phenotypes of OA are known to demonstrate familial aggregation. In an attempt to determine where the earliest structural changes occur in medial compartment knee OA, a cohort of patients selected only for their family history of the disease were developed. This cohort was compared to spouse controls for the presence of knee OA, as well as meniscal extrusion and long leg alignment. In addition, a functional analysis of their cartilage was performed. This cohort was not shown to be at increased risk of disease compared to controls. Discussion of the possible reasons for this finding is presented. Early knee osteoarthritis is a considerable clinical problem. This thesis has aided the understanding of the condition by firstly defining the radiological description of these patients. Secondly, their cross sectional and longitudinal symptom profile have been described for the first time. In addition, the presence of an extruded meniscus has been demonstrated as a substantial risk factor for the disease. Finally, family history has not been demonstrated as a risk factor for the disease within the limits of the study described here. Future work has been proposed.