Movement effects on the flow physics and nutrient delivery in engineered valvular tissues

Mechanical conditioning has been shown to promote tissue formation in a wide variety of tissue engineering efforts. However the underlying mechanisms by which external mechanical stimuli regulate cells and tissues are not known. This is particularly relevant in the area of heart valve tissue engineering (HVTE) owing to the intense hemodynamic environments that surround native valves. Some studies suggest that oscillatory shear stress (OSS) caused by steady flow and scaffold flexure play a critical role in engineered tissue formation derived from bone marrow derived stem cells (BMSCs). In addition, scaffold flexure may enhance nutrient (e.g. oxygen, glucose) transport. In this study, we computationally quantified the i) magnitude of fluid-induced shear stresses; ii) the extent of temporal fluid oscillations in the flow field using the oscillatory shear index (OSI) parameter, and iii) glucose and oxygen mass transport profiles. Noting that sample cyclic flexure induces a high degree of oscillatory shear stress (OSS), we incorporated moving boundary computational fluid dynamic simulations of samples housed within a bioreactor to consider the effects of: 1) no flow, no flexure (control group), 2) steady flow-alone, 3) cyclic flexure-alone and 4) combined steady flow and cyclic flexure environments. We also coupled a diffusion and convention mass transport equation to the simulated system. We found that the coexistence of both OSS and appreciable shear stress magnitudes, described by the newly introduced parameter OSI-:τ: explained the high levels of engineered collagen previously observed from combining cyclic flexure and steady flow states. On the other hand, each of these metrics on its own showed no association. This finding suggests that cyclic flexure and steady flow synergistically promote engineered heart valve tissue production via OSS, so long as the oscillations are accompanied by a critical magnitude of shear stress. In addition, our simulations showed that mass transport of glucose and oxygen is enhanced by sample movement at low sample porosities, but did not play a role in highly porous scaffolds. Preliminary in-house in vitro experiments showed that cell proliferation and phenotype is enhanced in OSI-:τ: environments.^

Interspecies study of the enteric nervous system and related pathologies

The enteric nervous system (ENS) modulates a number of digestive functions including well known ones, i.e. motility, secretion, absorption and blood flow, along with other critically relevant processes, i.e. immune responses of the gastrointestinal (GI) tract, gut microbiota and epithelial barrier . The characterization of the anatomical aspects of the ENS in large mammals and the identification of differences and similarities existing between species may represent a fundamental basis to decipher several digestive GI diseases in humans and animals. In this perspective, the aim of the present thesis is to highlight the ENS anatomical basis and pathological aspects in different mammalian species, such as horses, dogs and humans. Firstly, I designed two anatomical studies in horses:  “Excitatory and inhibitory enteric innervation of horse lower esophageal sphincter”.  “Localization of 5-hydroxytryptamine 4 receptor (5-HT4R) in the equine enteric nervous system”. Then I focused on the enteric dysfunctions, including:  A primary enteric aganglionosis in horses: “Extrinsic innervation of the ileum and pelvic flexure of foals with ileocolonic aganglionosis”.  A diabetic enteric neuropathy in dogs: “Quantification of nitrergic neurons in the myenteric plexus of gastric antrum and ileum of healthy and diabetic dogs”.  An enteric neuropathy in human neurological patients: “Functional and neurochemical abnormalities in patients with Parkinson's disease and chronic constipation”. The physiology of the GI tract is characterized by a high complexity and it is mainly dependent on the control of the intrinsic nervous system. ENS is critical to preserve body homeostasis as reflect by its derangement occurring in pathological conditions that can be lethal or seriously disabling to humans and animals. The knowledge of the anatomy and the pathology of the ENS represents a new important and fascinating topic, which deserves more attention in the veterinary medicine field.

Bond behaviour and kb factor in GFRP rebars casted in concrete

A proper bond between reinforcement and concrete is key for an appropriate composite action of both materials in reinforced concrete structures. However, to-date limited studies exist on bond of fiber reinforced polymer (FRP) bars in concrete members under flexure. In this paper, the bond strength developed by FRP and steel rebars is evaluated and compared, by testing reinforced concrete beams under three point bending load. The investigation included several beams that were 183 cm long × 15 cm wide × 36 cm deep: many of them were reinforced with sand coated GFRP rebars, while steel was used to reinforce the remaining ones. For each of the reinforcing systems, various different embedded lengths were tested. The beams were tested under a 3-point-bending setup and they were monitored using several measuring devices: LVDTS, potentiometers and strain gauges. Preliminary results show that the GFRP rebars have lower bond capacity than the ones made of steel. Moreover, it was inferred that the embedded lengths suggested by actual code provisions for GFRP rebars are too conservative.

Design of compliant mechanisms and their application to morphing wing technology

This thesis describes a study conducted for the development of a new approach for the design of compliant mechanisms. Currently compliant mechanisms are based on a 2.5D design method. The applications for which compliant mechanisms can be used this way, is limited. The proposed research suggests to use a 3D approach for the design of CM’s, to better exploit its useful properties. To test the viability of this method, a practical application was chosen. The selected application is related to morphing wings. During this project a working prototype of a variable sweep and variable AoA system was designed and made for an SUAV. A compliant hinge allows the system to achieve two DOF. This hinge has been designed using the proposed 3D design approach. To validate the capabilities of the design, two methods were used. One of these methods was by simulation. By using analysis software, a basic idea could be provided of the stress and deformation of the designed mechanism. The second validation was done by means of AM. Using FDM and material jetting technologies, several prototypes were manufactured. The result of the first model showed that the DOF could be achieved. Models manufactured using material jetting technology, proved that the designed model could provide the desired motion and exploit the positive characteristics of CM. The system could be manufactured successfully in one part. Being able to produce the system in one part makes the need for an extensive assembly process redundant. This improves its structural quality. The materials chosen for the prototypes were PLA, VeroGray and Rigur. The material properties were suboptimal for its final purpose, but successful results were obtained. The prototypes proved tough and were able to provide the desired motion. This proves that the proposed design method can be a useful tool for the design of improved CM’s. Furthermore, the variable sweep & AoA system could be used to boost the flight performance of SUAV’s.

Numerical prediction of the lateral displacement capacity of flexural reinforced concrete shear walls

Previous earthquakes showed that shear wall damage could lead to catastrophic failures of the reinforced concrete building. The lateral load capacity of shear walls needs to be estimated to minimize associated losses during catastrophic events; hence it is necessary to develop and validate reliable and stable numerical methods able to converge to reasonable estimations with minimum computational effort. The beam-column 1-D line element with fiber-type cross-section model is a practical option that yields results in agreement with experimental data. However, shortcomings of using this model to predict the local damage response may come from the fact that the model requires fine calibration of material properties to overcome regularization and size effects. To reduce the mesh-dependency of the numerical model, a regularization method based on the concept of post-yield energy is applied in this work to both the concrete and the steel material constitutive laws to predict the nonlinear cyclic response and failure mechanism of concrete shear walls. Different categories of wall specimens known to produce a different response under in plane cyclic loading for their varied geometric and detailing characteristics are considered in this study, namely: 1) scaled wall specimens designed according to the European seismic design code and 2) unique full-scale wall specimens detailed according to the U.S. design code to develop a ductile behavior under cyclic loading. To test the boundaries of application of the proposed method, two full-scale walls with a mixed shear-flexure response and different values of applied axial load are also considered. The results of this study show that the use of regularized constitutive models considerably enhances the response predictions capabilities of the model with regards to global force-drift response and failure mode. The simulations presented in this thesis demonstrate the proposed model to be a valuable tool for researchers and engineers.