The Mechanics And Molecular Regulation Of Heart Valve Morphogenesis

Congenital heart defects (CHD) affect over 1% of the American population and are the origin of substantial healthcare costs. A majority of these defects involve malformations of the valvuloseptal apparatus, which is the precursor to the valves of the heart. Due to the necessity of valves for proper heart function, most moderate to severe valve defects require surgical intervention. Corrective surgery is costly and can result in complications and/or restrictions on the patient's lifestyle. Current genetic evidence for CHD is inadequate to explain the variety and prevalence of these defects, suggesting that misguided molecular and mechanical signaling may be responsible. Unfortunately, the role of mechanical and molecular signaling in normal valve development is only beginning to be elucidated, making the detection of defective valves difficult. An understanding of these mechanical and molecular cues and their effect on valve mechanics in normal development is essential for effective treatment of CHDs. In this dissertation, we focus on the capacity of mechanical and molecular signals to direct valve morphology and mechanical properties. We first validate two mechanical testing techniques to characterize the mechanical properties of avian valves through development. This revealed a monotonic increase in valve stiffness which was concomitant with a rapid transition from globular to planar geometry. We then investigated the capacity of transforming growth factor beta 3 (TGF[beta] 3) and serotonin (5-HT) to stimulate biomechanical remodeling in avian valves. TGF[beta] 3 significantly increased valve stiffness through cell contraction, proliferation, and extracellular matrix synthesis. 5-HT modulated TGF[beta] 3 remodeling in both in vitro and in vivo models. This demonstrated a plausible molecular mechanism for the stiffness increase observed during development. To investigate the role of mechanical signaling, we developed a model of growth and remodeling (shape change) that is driven by mechanical stimuli. The consequences of particular assumptions about growth were illustrated with numerical examples. We then built a computational model of valve growth involving both the fluid and solid domains of the atrioventricular (AV) canal and valve. The distribution of the fluid loads on the valve was correlated with the natural morphology of the valve. The computational framework allowed the effects of pressure and shear tractions to be individually interpreted. These results provided a potential mechanical mechanism to explain the valve morphology observed during development. The dissertation concludes with a chapter on teaching and outreach that stemmed from my involvement in the NSF GK-12 program. Conclusions and future directions are discussed

Autonomous motility of polymer films coupled to stimuli gradients

Adaptive soft materials exhibit a diverse set of behaviors including reconfiguration, actuation, and locomotion. These responses are typically optimized in isolation. Here, we explore the interrelation between these behaviors by developing a behavioral phase diagram for hygromorphic polymer films. We determine that the dynamic behaviors are a result of not only a response to, but also an interaction with a humidity gradient, which can be tuned via control of the environment and film characteristics, including size, permeability and coefficient of hygroscopic expansion to target a desired behavior such as multi-modal locomotion. Using the improved understanding of stimuli interactive materials gained from our study of monolithic polymer films, we demonstrate how robust composites can be designed to exhibit autonomous, environmentally-responsive behaviors, and how these concepts can be incorporated into origami structures to engineer the extent and sequence of motions

Towards enduring autonomous robots via embodied energy.

Autonomous robots comprise actuation, energy, sensory and control systems built from materials and structures that are not necessarily designed and integrated for multifunctionality. Yet, animals and other organisms that robots strive to emulate contain highly sophisticated and interconnected systems at all organizational levels, which allow multiple functions to be performed simultaneously. Herein, we examine how system integration and multifunctionality in nature inspires a new paradigm for autonomous robots that we call Embodied Energy. Whereas most untethered robots use batteries to store energy and power their operation, recent advancements in energy-storage techniques enable chemical or electrical energy sources to be embodied directly within the structures and materials used to create robots, rather than requiring separate battery packs. This perspective highlights emerging examples of Embodied Energy in the context of developing autonomous robots

Heart function and hemodynamic analysis for zebrafish embryos

The Zebrafish has emerged to become a powerful vertebrate animal model for cardiovascular research in recent years. Its advantages include easy genetic manipulation, transparency, small size, low cost, and the ability to survive without active circulation at early stages of development. Sequencing the whole genome and identifying ortholog genes with human genome made it possible to induce clinically relevant cardiovascular defects via genetic approaches. Heart function and disturbed hemodynamics need to be assessed in a reliable manner for these disease models in order to reveal the mechanobiology of induced defects. This effort requires precise determination of blood flow patterns as well as hemodynamic stress (i.e., wall shear stress and pressure) levels within the developing heart. While traditional approach involves time-lapse brightfield microscopy to track cell and tissue movements, in more recent studies fast light-sheet fluorescent microscopes are utilized for that purpose. Integration of more complicated techniques like particle image velocimetry and computational fluid dynamics modeling for hemodynamic analysis holds a great promise to the advancement of the Zebrafish studies. Here, we discuss the latest developments in heart function and hemodynamic analysis for Zebrafish embryos and conclude with our future perspective on dynamic analysis of the Zebrafish cardiovascular system.We would like to thank to Qatar University Biomedical Research Center team for the study; Dr. Asma Alhani, Dr. Gheeyath Nasral-lah, Ms. Sahar IsaDas, Dr. Hany Mady, Dr. Hadi Yassine, Dr. Nahla Eltai for scientific support; and Ms. Naiema Al-Meer, Ms. Maria Khalid Smatti, and Ms. Fadheela Mohammad for administrative support. This research was supported by Qatar University internal grants (QUST-BRC-SPR\2017-1 and QUUG-BRC-2017-3 to H.C.Y.).Scopu

Laser writing of electronic circuitry in thin film molybdenum disulfide: A transformative manufacturing approach

Electronic circuits, the backbone of modern electronic devices, require precise integration of conducting, insulating, and semiconducting materials in two- and three-dimensional space to control the flow of electric current. Alternative strategies to pattern these materials outside of a cleanroom environment, such as additive manufacturing, have enabled rapid prototyping and eliminated design constraints imposed by traditional fabrication. In this work, a transformative manufacturing approach using laser processing is implemented to directly realize conducting, insulating, and semiconducting phases within an amorphous molybdenum disulfide thin film precursor. This is achieved by varying the incident visible (514 nm) laser intensity and raster-scanning the thin film a-MoS2 sample (900 nm thick) at different speeds for micro-scale control of the crystallization and reaction kinetics. The overall result is the transformation of select regions of the a-MoS2 film into MoO2, MoO3, and 2H-MoS2 phases, exhibiting conducting, insulating, and semiconducting properties, respectively. A mechanism for this precursor transformation based on crystallization and oxidation is developed using a thermal model paired with a description of the reaction kinetics. Finally, by engineering the architecture of the three crystalline phases, electrical devices such as a resistor, capacitor, and chemical sensor were laser-written directly within the precursor film, representing an entirely transformative manufacturing approach for the fabrication of electronic circuitry

Design of Soft Origami Mechanisms with Targeted Symmetries

The integration of soft actuating materials within origami-based mechanisms is a novel method to amplify the actuated motion and tune the compliance of systems for low stiffness applications. Origami structures provide natural flexibility given the extreme geometric difference between thickness and length, and the energetically preferred bending deformation mode can naturally be used as a form of actuation. However, origami fold patterns that are designed for specific actuation motions and mechanical loading scenarios are needed to expand the library of fold-based actuation strategies. In this study, a recently developed optimization framework for maximizing the performance of compliant origami mechanisms is utilized to discover optimal actuating fold patterns. Variant patterns are discovered through exploring different symmetries in the input and output conditions of the optimization problem. Patterns designed for twist (rotational symmetry) yield significantly better performance, in terms of both geometric advantage and energy requirements, than patterns exhibiting vertical reflection symmetries. The mechanical energy requirements for each design are analyzed and compared for both the small and large applied displacement regimes. Utilizing the patterns discovered through optimization, the multistability of the actuating arms is demonstrated empirically with a paper prototype, where the stable configurations are accessed through local vertex pop-through instabilities. Lastly, the coupled mechanics of fold networks in these actuators yield useful macroscopic motions and can achieve stable shape change through accessing the local vertex instabilities. This survey of origami mechanisms, energy comparison, and multistability characterization provides a new set of designs for future integration with soft actuating materials

Origami-Inspired Frequency Selective Surface with Fixed Frequency Response under Folding

Filtering of electromagnetic signals is key for improved signal to noise ratios for a broad class of devices. However, maintaining filter performance in systems undergoing large changes in shape can be challenging, due to the interdependency between element geometry, orientation and lattice spacing. To address this challenge, an origami-based, reconfigurable spatial X-band filter with consistent frequency filtering is presented. Direct-write additive manufacturing is used to print metallic Archimedean spiral elements in a lattice on the substrate. Elements in the lattice couple to one another and this results in a frequency selective surface acting as a stop-band filter at a target frequency. The lattice is designed to maintain the filtered frequency through multiple fold angles. The combined design, modeling, fabrication, and experimental characterization results of this study provide a set of guidelines for future design of physically reconfigurable filters exhibiting sustained performance