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In this work we study the supermanoeuvrability of a biomimetic morphing-wing case study aircraft system. Analytical and computational models of biomimetic flight dynamics are developed, utilising multibody dynamics, computational fluid dynamics, and reduced-order aerodynamic models; and validated with respect to experimentally-derived flight dynamics of a Pioneer RQ-2 UAV. These models are used to explore the capability of this system for a wide range of biological and other supermanoeuvres: multi-axis quasistatic nose-pointing-and-shooting (NPAS)/direct force capability; multi-axis rapid-nose-pointing-and-shooting (RaNPAS) including Pugachev's cobra; ballistic transition; and anchor turning. Novel contributions include the development of transient aerodynamic models for a three-dimensional flight-simulation context; the development of novel methods for assessing transient model validity; the development of improved methods of quaternion variational integration; the development of quasi-trim and continuation-based methods for the design, exploration, analysis and control of manoeuvres in biomimetic morphing-wing systems; an assessment of the complex spiral mode stability effects present in asymmetrically-morphed system trim states; and a demonstration of the wide-ranging potential for advanced supermanoeuvrability in biomimetic morphing-wing systems. Industrial applications include the design of high-precision guided missiles for use in complex, e.g. urban, environments.

Demand for robotic solutions to problems in every area of society has been rapidly increasing. Some notable examples include providing independence and care to the elderly, managing degrading farm land, and reducing the risk to human life with agile robots for search and rescue. Many of these areas will require robots to either work alongside humans, or in environments that are unstructured. For these an artificial sense of touch will be crucial. Tactile sensing is a young field of research when compared to other sensing fields like computer vision. But just like computer vision, tactile sensing will open up important doors for robotics systems. Tactile provides an active sense for robots, allowing contact level perception on its influence on the world. It is this sensing and understanding of environmental influence that can be utilised for manipulation. This thesis presents novel developments in tactile sensing hardware, perception, and deployment. The work demonstrates the development of the TacTip tactile sensor to be better suited to rapid prototyping and complex morphologies. This is achieved by redeveloping the TacTip technology to be bot modular and 3D printable in a multi-material printer. Ultimately this allowed the for exploration the effects of biomimetic fingerprints on tactile perception of varies spatial scales. Demonstrating improvements in acuity of location perception with its inclusion. An investigation into using active perception algorithms for active manipulation is explored. Where the principle that existing algorithms that provide control for perception can be used such that perception for control is achieved. The work demonstrated the successful rolling of a cylinder on a table top using only tactile sensing, and highlights that the methods have a trade off between accuracy and reaction time. To improve the generality of the TacTip sensors tactile sensing, I present the development of a novel method for inferring a third dimension to the sensor data. This method deploys the mathematical principle of voronoi tessellation to the point data outputted from the sensor. This tessellation creates cells around each point, the areas of which can be interpolated to crate a 3D surface representation of the data. Ultimately, along with exploration of the raw point data, tactile features such as shear, pressure, and contact locations could be inferred with out the use of data intensive machine learning techniques. Lastly, this thesis present a fully tactile seven degree of freedom hand, fully equipped with the new TacTip developments and generalised feature inference. The hand was designed to be highly tactile, dexterous and relatively inexpensive tool. The hand is benchmarked on the YCB objectset with a closed loop adaptive grasp controller which demonstrates its viability for starting to explore tactile dexterous manipulation. Overall this thesis demonstrates developments in tactile sensing with accurate location perception, feature perception, simple manipulations, and grasp adaptation. All of these are components necessary for reaching the ultimate goal and bigger challenge of complex dexterous tactile manipulation.

Due to an aging population and younger patients presenting with musculoskeletal disorders, there is a need for orthopaedic implants with improved healing rates and longer implant life. Numerous research has developed implant surfaces with micro-topography and biomolecules to imitate the native extra cellular matrix (also known as biomimetic surfaces). This research has utilised such a biomimetic approach by immobilising the cell adhesive peptide, RGD (Arginine-Glycine-Aspartic Acid), to a titanium alloy Ti6Al4V surface. This research polymerised Hyperbranched Polyglycerol (HBPG) from the titanium surface using Ring Opening Multi-Branching Polymerisation (ROMBP). HBPG is a biologically compatible and non-toxic synthetic biopolymer, able to reduce non-specific protein adsorption, increase the titanium surface wetting (hydrophilicity), thereby limiting foreign body reactions. Extensive hydroxyl groups at the periphery of HBPG provides conjugation sites for biomolecule attachment. In this work the RGD peptide was conjugated to the polymer via a siloxane layer. This research developed a novel passivation solution for the preparation of the titanium alloy surface, using a mixture of hydrogen peroxide and nitric acid (a passivation mixture not used in the literature). This novel mixture was shown to etch the titanium surface, producing micro and nano surface features, both of which have been shown to improve cellular function in the literature. The hydrogen peroxide/nitric acid solution showed extensive oxidising ability on titanium, leading to the formation of reactable hydroxyl groups. Contact-angle measurements showed that the novel passivating solution produces a hydrophilic surface similar to that of peroxidation for 12-hours, but achieved in only 2-hours. In conjunction with the etching and oxidising abilities of hydrogen peroxide, the nitric acid reacts with the titanium surface, leading to the formation of a protective titanium oxide layer, enhancing corrosion resistance and improving biocompatibility. Biological investigations with the pre-osteoblast cell line MC3T3-E1 showed greater osteoblast cell attachment and adhesion strength, as well as improved bone matrix mineralisation on the passivated titanium surface functionalised with HBPG and the RGD peptide, compared to the raw and passivated titanium surfaces. Antibacterial testing of HBPG revealed substantially reduced bacterial cell colonies on the passivated/polymerised titanium surface, possibly arising from electrostatic and hydrophobic repulsion. This research has successfully developed a new titanium passivation solution (hydrogen peroxide/nitric acid) that can yield a contact-angle of around 35° in just 2-hours, rivalling the Piranha solution. The successful immobilisation of a cyclic RGD (cyclic-RGDfc) to a titanium surface functionalised with HBPG, has been shown in this research to drastically improve mineralised bone matrix production from the MC3T3-E1 cell line. This indicates earlier osseointegration of the implant may be possible, thereby improving patient healing times.

Molecularly imprinted polymers (MIPs) are biomimetic sensing elements that combine the accuracy and highly specific binding affinity of a biosensor, with the robustness and reusability associated with artificial electrochemical sensors. This thesis investigates the application of a MIP sensor to address the challenge of phosphate detection in precision agriculture. Traditional chemical sensing approaches using portable electrochemical sensors display a significant cross-interference between inorganic phosphate and other nutrient ions. This is due to the low position of phosphate in the Hofmeister Selectivity Series for anions, its high electronegativity and its pH dependent structure, resulting in a molecule that is very difficult to detect. To address this challenge, a sensor was created by spin coating a phosphate selective MIP onto a substrate containing a series of electrodes. These electrode devices allowed for electrical measurements to be taken using an inductance, capacitance and resistance (LCR) testing station, and to observe the change in the materials dielectric constant as the binding sites become occupied by the target analyte. The devices underwent several design reiterations to produce an optimised setup consisting of 100 interdigitated chrome electrodes with a width of 1 μm and a separation distance of 1 μm on a quartz substrate. The final electrode design was used to carry out a nutrient cross-interference study across several polymer permutations. The purpose of this was to develop an optimised MIP formulation for binding specifically to inorganic phosphate ions. From this study, an optimal phosphate selective MIP was identified, based upon a binding site constructed from methacrylic acid around a diphenyl phosphate template molecule. During capacitance measurements, this MIP formulation demonstrated a clear preferential response to phosphate (1610 pF) over the average capacitance results observed following exposure to the competing nitrate (1286 pF) and sulphate (1212 pF) nutrients tested in the cross-interference study.

Much of our knowledge of cellular biology arises from direct observation of active cellular functions. Tools and techniques have steadily developed over the past several hundreds of years to aid in our understanding and control of the nanoworld and are referred to as nanotechnologies. In the context of nanotechnology, DNA is not used as a carrier for genetic information (as it is in cell), but as a construction material. DNA offers unprecedented control over the construction of simplified biomimetic models for the study of biological processes. This thesis first introduces and defines the field of DNA nanotechnology, with particular emphasis on the interaction of snthetic DNA nanostructures with biological membranes. Inspired by the protein clathrin, three-fold symmetric DNA tile made of eight, short DNA strands and capable of polymerising is described and studied, with the aim to interact with and controllably bend a membrane bilayer. This structure presented challenges during construction so an enhanced three-armed DNA structure built with DNA origami was designed. The succesful assembly of a rigid and functionalisable nanostructure is described. This origami structure was polymerised into large constructs in solution and on a supported lipid membrane. The shape of the structure was modulated to vary its curvature and apply a bending force to a lipid vesicle when anchored to it. Following the conclusion of this study, we present the construction of a small, unique DNA structure for enhanced electron microscopy imaging in cell lysate. This project is part of a developing technique to couple the interaction specificity of dyes in super-resolution microscopy and the high-resolution output of electron microscopy. Finally, the optimisation procedures and recommendations for TEM imaging of samples of DNA origami and lipid structures are discussed.

Biomimetic synthesis is the branch of synthetic organic chemistry which attempts to learn from nature into order to solve the challenges of chemical synthesis. This thesis describes application of biomimetic principles to the total synthesis of three phenylethanoid alkaloid natural products: incargranine B; millingtonine and incargranine A. Chapter 1 provides a general introduction to the area. Specific introductions can be found at the start of each chapter. Chapter 1 introduces the concept of biomimicry and provides a brief overview of the development of the underlying concepts and terminology. The major biosynthetic pathways involved in the production of incargranine B, millingtonine and incargranine A (shikimic acid, ornithine alkaloids) are also introduced. Chapter 2 discusses the synthesis of incargranine B. Biosynthetic analysis of this dimeric alkaloid led us to question its structural assignment and suggest a structural revision. This speculative reassignment was validated through a biomimetic total synthesis of our proposed structure. Incargranine B was successfully prepared in a longest linear sequence of six steps, forming three new rings, four bonds and three contiguous stereocentres in a single biomimetic domino condensation/Mannich/SEAr sequence. Chapter 3 describes the synthesis of millingtonine. We proposed that millingtonine is biosynthetically related to incargranine B through a divergent/re-convergent network of pathways. Synthetic exploration of this hypothesis culminated in the total synthesis of millingtonine and discovery of an unanticipated biosynthetic intermediate, dia-millingtonine, which we propose as a previously unidentified natural product. . Chapter 4 details the synthesis of incargranine A. Incorporating dia-millingtonine into our biosynthetic hypothesis allowed the development of a four step bioimimetic total syntheses of incargranine A which was scaled-up to provide over one gram of natural product. Chapter 5 summarises the work presented and provides a perspective on its contribution to the field.

Breast implant capsular contracture (CC) formation is a significant clinical complication post augmentation/reconstruction, which often necessitates re-operation. CC, which occurs in over half of patients post augmentation, is the formation of a fibrous internal capsule which constricts around the prosthesis leading to firmness, deformity and pain. The pathoetiology of CC is poorly understood with minimal understanding of the triggers, signalling pathways or dysregulated genes implicated in its formation. Therefore, the first aim of the present thesis was to investigate biomarkers implicated in CC formation, through whole genome microarray, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) on capsule samples ranging from normal capsules (Baker Grade 1) to severely contracted capsules (Baker Grade 4). After targeted enrichment analysis, microarray identified 6 genes which were significantly dysregulated in contracted capsules. After further genomic and proteomic validation, two potential diagnostic, prognostic or therapeutic biomarkers for CC, interleukin 8 (IL8) and tissue inhibitor of metalloproteinase 4 (TIMP 4), were identified as being significantly dysregulated in CC. However, the role of each of the multiple cell types which populate a contracted capsule has yet to be determined. Therefore, the role of capsular fibroblasts was investigated using immunocytochemistry, qRT-PCR, cytokine arrays and a fibroblast populated 3D collagen matrix. IL8 and TIMP were investigated, in addition to other pro-fibrotic and pro-inflammation related candidates, to identify the role of breast capsule fibroblasts in CC formation. Normal breast fibroblast populated collagen matrices were significantly more contracted after supplementation with contracted-capsule fibroblast conditioned media, in comparison to normal growth media. It was discovered that breast-derived fibroblasts were potentially instigating and/or perpetuating CC through the transformation of normal breast fibroblasts into contracted capsule fibroblast like cells, via a paracrine signalling mechanism. The results of this work on capsular fibroblasts, and the previous work on capsular tissue, increased our understanding of the cell types and signalling molecules which are dysregulated leading to CC formation. Therefore, a novel silicone implant surface potentially capable of averting CC formation could be fabricated. Acellular dermal matrix (ADM) has been used as an adjunct in breast implant augmentation/reconstruction resulting in reduced rates of CC formation. Therefore, the micro and nanoscale topography of ADM was reproduced in a silicone surface, through a novel fabrication technique utilising comprehensive characterisation of ADM with atomic force microscopy (AFM), maskless grayscale photolithography, modified deep reactive ion etching (DRIE) and replica moulding. The features of ADM were successfully re-created in silicone to within 5 nm (Sa) and 655 nm (Sz), at a length scale of 90x90 µm2. Biological evaluation revealed that ADM PDMS surfaces promoted cell adhesion, proliferation and survival when compared to commercially available implant surfaces while cell adhesion regulating genes were upregulated and pro-inflammatory/pro-fibrotic related genes were downregulated. A reduced inflammatory cytokine response was also observed. This study demonstrates that biomimetic prosthetic implant surfaces might significantly attenuate the acute in vitro foreign body reaction to silicone. In conclusion, the results of the present thesis have enhanced our knowledge and understanding of the pathological cellular and molecular mechanisms leading to CC, in addition to the design and development of a novel, biomimetic implant surface that is potentially capable of averting the identified pathological processes in vivo.

This thesis proposes a novel set of generic and compact biologically plausible VLSI (Very Large Scale Integration) neural circuits, suitable for implementing a parallel VLSI network that closely resembles the function of a small-scale neocortical network. The proposed circuits include a cortical neuron, two different long-term plastic synapses and four different short-term plastic synapses. These circuits operate in accelerated-time, where the time scale of neural responses is approximately three to four orders of magnitude faster than the biological-time scale of the neuronal activities, providing higher computational throughput in computing neural dynamics. Further, a novel biological-time cortical neuron circuit with similar dynamics as of the accelerated-time neuron is proposed to demonstrate the feasibility of migrating accelerated-time circuits into biological-time circuits. The fabricated accelerated-time VLSI neuron circuit is capable of replicating distinct firing patterns such as regular spiking, fast spiking, chattering and intrinsic bursting, by tuning two external voltages. It reproduces biologically plausible action potentials. This neuron circuit is compact and enables implementation of many neurons in a single silicon chip. The circuit consumes extremely low energy per spike (8pJ). Incorporating this neuron circuit in a neural network facilitates diverse non-linear neuron responses, which is an important aspect in neural processing. Two of the proposed long term plastic synapse circuits include spike-time dependent plasticity (STDP) synapse, and dopamine modulated STDP synapse. The short-term plastic synapses include excitatory depressing, inhibitory facilitating, inhibitory depressing, and excitatory facilitating synapses. Many neural parameters of short- and long- term synapses can be modified independently using externally controlled tuning voltages to obtain distinct synaptic properties. Having diverse synaptic dynamics in a network facilitates richer network behaviours such as learning, memory, stability and dynamic gain control, inherent in a biological neural network. To prove the concept in VLSI, different combinations of these accelerated-time neural circuits are fabricated in three integrated circuits (ICs) using a standard 0.35 µm CMOS technology. Using first two ICs, functions of cortical neuron and STDP synapses have been experimentally verified. The third IC, the Cortical Neural Layer (CNL) Chip is designed and fabricated to facilitate cortical network emulations. This IC implements neural circuits with a similar composition to the cortical layer of the neocortex. The CNL chip comprises 120 cortical neurons and 7 560 synapses. Many of these CNL chips can be combined together to form a six-layered VLSI neocortical network to validate the network dynamics and to perform neural processing of small-scale cortical networks. The proposed neuromorphic systems can be used as a simulation acceleration platform to explore the processing principles of biological brains and also move towards realising low power, real-time intelligent computing devices and control systems.

Mobile robots for rough terrain are of interest to researchers as their range of possible uses is large, including exploration activities for inhospitable areas on Earth and on other planets and bodies in the solar system, searching in disaster sites for survivors, and performing surveillance for military applications. Nature generally achieves land movement by walking using legs, but additional modes such as climbing, jumping and rolling are all produced from legs as well. Robotics tends not to use this integrated approach and adds additional mechanisms to achieve additional movements. The spherical device described within this thesis, called Jollbot, integrated a rolling motion for faster movement over smoother terrain, with a jumping movement for rougher environments. Jollbot was developed over three prototypes. The first achieved pause-and-leap style jumps by slowly storing strain energy within the metal elements of a spherical structure using an internal mechanism to deform the sphere. A jump was produced when this stored energy was rapidly released. The second prototype achieved greater jump heights using a similar structure, and added direction control to each jump by moving its centre of gravity around the polar axis of the sphere. The final prototype successfully combined rolling (at a speed of 0.7 m/s, up 4° slopes, and over 44 mm obstacles) and jumping (0.5 m cleared height), both with direction control, using a 0.6 m spherical spring steel structure. Rolling was achieved by moving the centre of gravity outside of the sphere’s contact area with the ground. Jumping was achieved by deflecting the sphere in a similar method to the first and second prototypes, but through a larger percentage deflection. An evaluation of existing rough terrain robots is made possible through the development of a five-step scoring system that produces a single numerical performance score. The system is used to evaluate the performance of Jollbot.

This project investigates the experience of physiological discomfort during travel through an urban environment such as London or New York in winter. The over and underground networks that lace a current metropolis, form vital passages that lead the traveller though a multitude of spaces each defined by unique temperature, humidity and activity level. It is impossible to predict possible eventualities and consequently accommodate in a selection of clothing to ensure physiological comfort. Modular clothing assemblies are currently employed for the management of physiological comfort to adjust the insulation and ventilation properties of a clothing system and rely on combinations of behavioural methods and textile properties. This method is compromised by factors such as limited availability of space and wearer’s ability to detect and respond to the onset of discomfort sensations. Current smart systems rely on temperature as a stimulus for actuation. Experimental work suggests that humidity is a more suitable trigger. Botanical mechanisms that employ hygroscopic expansion/contraction for seed and spore deployment were identified as paradigms for the development of a smart textile system. Biomimetic analysis of these natural mechanisms inspired the design of a textile prototype able to adapt its water vapour resistance in response to humidity changes in the microclimate of the clothing system. The resulting structure decreases its permeability to air by 20% gradually as relative humidity increases from 60% to 90%.

This thesis addresses orchestration of servers amongst multiple co-hosted internet services such as e-Banking, e-Auction and e-Retail in hosting centres. The hosting paradigm entails levying fees for hosting third party internet services on servers at guaranteed levels of service performance. The orchestration of server ensemble in hosting centres is considered in the context of maximising the hosting centre's revenue over a lengthy time horizon. The inspiration for the server orchestration approach proposed in this thesis is drawn from nature and generally classed as swarm intelligence, specifically, sophisticated collective behaviour of social insects borne out of primitive interactions amongst members of the group to solve problems beyond the capability of individual members. Consequently, the approach is self-organising, adaptive and robust. A new scheme for server ensemble orchestration is introduced in this thesis. This scheme exploits the many similarities between server orchestration in an internet hosting centre and forager allocation in a honeybee (Apis mellifera) colony. The scheme mimics the way a honeybee colony distributes foragers amongst flower patches to maximise nectar influx, to orchestrate servers amongst hosted internet services to maximise revenue. The scheme is extended by further exploiting inherent feedback loops within the colony to introduce self-tuning and energy-aware server ensemble orchestration. In order to evaluate the new server ensemble orchestration scheme, a collection of server ensemble orchestration methods is developed, including a classical technique that relies on past history to make time varying orchestration decisions and two theoretical techniques that omnisciently make optimal time varying orchestration decisions or an optimal static orchestration decision based on complete knowledge of the future. The efficacy of the new biomimetic scheme is assessed in terms of adaptiveness and versatility. The performance study uses representative classes of internet traffic stream behaviour, service user's behaviour, demand intensity, multiple services co-hosting as well as differentiated hosting fee schedule. The biomimetic orchestration scheme is compared with the classical and the theoretical optimal orchestration techniques in terms of revenue stream. This study reveals that the new server ensemble orchestration approach is adaptive in a widely varying external internet environments. The study also highlights the versatility of the biomimetic approach over the classical technique. The self-tuning scheme improves on the original performance. The energy-aware scheme is able to conserve significant energy with minimal revenue performance degradation. The simulation results also indicate that the new scheme is competitive or better than classical and static methods.

Bats are noted for having extremely powerful biosonar systems that enable them to move through and hunt through the thick foliage. They have a single emitter (mouth or nose) and two receivers in their biosonar system (ears). Some bat species, such as those belonging to the group's rhinophid and hipposiderid, feature intricate pinna motion patterns. These pinnae are divided into two groups: stiff movements and non-rigid motions. To understand how pinna sense worked has been studied in this thesis. The rigid pinna movements displayed a significantly different rotation, with revolutions axes spanning 180° in horizontal and curvature, according to axis-angle representations. The classification of landmarks on the pinna surface has explained two types of non-stiffed pinna movements. Additionally, a bio-inspired pinna has been used to explore the acoustic impact of the stiff pinna movements. All the given results showed precise accuracy in the motion of variance bats pinnae. The research initiative was initiated with a comprehensive exploration of various design concepts, primarily focused on elucidating the intricate interplay between actuator geometry and the resultant deformation of the pinna. Employing a structured design code facilitated the generation of an array of configurations, each subject to stringent conditions and parameter settings necessitating subsequent validation. After this design exploration, a tri-tiered hierarchy of forces, encompassing nominal, intermediate, and elevated magnitudes, was applied to instigate a systematic optimization process aimed at determining the most favorable deformation pattern. Computational simulations leveraging Finite Element Analysis (FEA) were conducted, accompanied by a rigorous material characterization procedure, to effectively quantify the extent of deformation across the array of configurations. A consequential phase of the investigation involved the implementation of Principal Component Analysis (PCA) to differentiate the inherent variability within the different deformation arrangements, shedding light on their relative structural and morphological distinctions. The culmination of the study encompassed the utilization of the Genetic Algorithm (GA), a sophisticated optimization technique, to facilitate the fine-tuning of deformation patterns in pursuit of the overarching goal: the deliberate induction of substantial and diverse variations in pinna morphology. In summary, the research trajectory progressed sequentially through design conceptualization, force-induced optimization, computational simulations incorporating FEA and material characterization, Variability analysis via PCA, and culminated in the deployment of the GA to achieve the prime objective of inducing pronounced variability in pinna configuration. The work was done as following, starting with design concepts, the main benefit of this is to understand how the geometry of actuator affects the pinna deformation. Using the design code to present several configurations that must have conditions and parameters to be validated. After that applying 3 different forces (zero, medium, and high) to get the optimization for pattern. Applying the FEA simulations with help of material characterization to display the displacement of the arrangements. Finally doing the Variability analysis by using the principal component analysis. Then concluding the work by using the Genetic algorithm for optimizations to reach the main goal which is large variability in the pinna shape.

The development of patient-specific implants for reconstructive applications involving unique deformities or injuries has demonstrated the promise of additive manufacturing (AM) in the medical setting. Biomimetic lattice structures can facilitate internal bone growth due to their porous nature, which can reduce stress shielding and improve the lifespan of an implant. In addition, pulsed electromagnetic field therapy can be implemented to accelerate the osseointegration process internally in the lattice structures by improving cellular proliferation and attachment. In this research, cubic and body-centered cubic (BCC) unit cell geometries were 3D printed using selective laser melting and biocompatible Ti-6Al-4V feedstock powder. The lattices were designed with four different pore sizes (400, 500, 600, and 900 µm, representing 40-90% porosity in a 10 mm cube). Compression and tensile testing were performed to evaluate the mechanical properties of the lattice structures, with results compared to human cancellous bone. SEM microstructural characterization of the manufactured lattices exhibited deviations in AM pore sizes and strut diameters when compared to original CAD designs in nTopology. It was found that the elastic modulus of human cancellous bone (10 - 900 MPa) could be matched for both tensile (92.7 - 129.6 MPa) and compressive (185.2 - 996.1 MPa) elastic modulus of cubic and BCC lattices. BCC lattices exhibited higher compressive properties over cubic, whereas cubic lattices exhibited superior tensile properties over BCC. To determine the effects of porosity and unit cell geometry on the osteogenesis of human MG-63 osteoblastic cell lines in vitro, glucose consumption, alkaline phosphate (ALP), and end-of-culture cell count activity was analyzed as markers for osteogenic growth. The results indicated that lattices with a 900 µm pore size exhibited the highest glucose consumption and the greatest change in alkaline phosphate activity when compared to other pore sizes, for both strut geometries. On average, the cubic unit cell geometry exhibited higher glucose consumption, and a larger cell count when compared to their counterparts with body-centered cubic strut geometries. Irrespective of a particular pore size or unit cell geometry, it was found that all lattices can promote osteogenic growth. A pulsed electromagnetic field (PEMF) was then applied (15 Hz, 300 µs pulse width, 20 VPP, 0.5 mT field intensity) to cell cultures in vitro (2 hours/day for 14 days) and compared to non-PEMF stimulated controls. The results indicated that PEMF had a greater impact on glucose concentration than ALP activity for all lattices. This may indicate that at lower field intensities, PEMF had an increased effect on the early formation (surface attachment) stage of bone cell differentiation.

Damage to our tissues occurs daily and must be repaired by the body in a timely manner in order to prevent infection and restore tissue integrity. Many cell types are involved in the healing process, but it is the cells of the stroma that are largely responsible for rebuilding fibrous tissue, which provides structure and support for all other cell types during healing. This dissertation focuses on stromal tissue repair, the rebuilding of fibrous tissue by fibroblasts following injury. Specifically, I focus on 1) models to study wound healing in vitro, and the specific biological processes of healing that each model captures, 2) the response of engineered stromal microtissues to different methods of injury, namely laceration and laser ablation, and the subsequent clearance and rebuilding of the extracellular matrix by fibroblasts, and 3) how different types of stromal cells and extracellular matrix proteins contribute to tissue repair in vitro.

Biomanufacturing is an approach to production that repurposes cellular metabolism to transform inexpensive, renewable resources into value-added chemicals. While recent efforts haverapidly expanded product scope and improved product yields, many products developed at lab scale fail to reach markets. This problem exists largely due to the staggering complexity of natural metabolism that distributes crucial resources, such as electrons, across the vast metabolic network. Natural metabolism relies on chemical compartmentalization of two redox cofactors, NAD+ and NADP+, to orchestrate the directions of life-essential redox reactions. These redox cofactors are insulated from each other to permit thermodynamically incompatible reactions to occur simultaneously and in the same space.Here, we investigate the recreation of this indispensable design in cellular metabolism,chemical compartmentalization by specific coenzymes, using a new-to-Nature redox cofactor, nicotinamide mononucleotide (NMN+). In Chapter 1, I introduce a framework to evaluate control of redox reaction equilbria and review relevant literature. In Chapter 2, we engineer the enzymes necessary to test our hypotheses on the control of redox reaction equilibria that can be achieved with noncanonical redox cofactors. In Chapter 3, we evaluate application of a complete toolkit for the modulation of NMNH/NMN+ ratio in vitro and in vivo, both in the presence of dramatically opposed NADH/NAD+ or NADPH/NADP+ ratios. In Chapter 4, I discuss efforts to engineer Escherichia coli ’s pyruvate dehydrogenase complex to specifically interface NMN+ in an effort to develop growth-coupled NMN+ reduction. Finally, in Chapter 5, I explore engineering the pyruvate dehydrogenase complex as a test-bed for extremely far-from-equilibrium redox biochemistry.This work presents the first generation of a full infrastructure of using NMN+ as anorthogonal redox cofactor with its designated electron source and electron sink. The work presented here focuses on applications that directly address limitations in biomanufacturing. However, looking far forward, access to genetically encoded tools for precise control of reduction potential in specific metabolic processes could also be essential for applications that address challenges in human health by precise maintenance of the delicate redox patterns that support life. This work aims to be a foundation upon which future orthogonal metabolic systems are established.

This research sets out to demonstrate the viability of parametric modeling for biomimetic sharkskin in the effort to reduce drag and create a self-cleaning surface. Multiple designs were created to be machined by Wire EDM on stainless steel and titanium and were comparatively tested. Limitations of current manufacturing processes to economically produce naturally occurring structures such as sharkskin, emphasize the need to be able to calculate the most accurate design for a given manufacturing process. By designing a simplified but parametrically consistent model compared to an accurately depicted 3D model of sharkskin, the textured samples produced can be further tested for drag reduction and hydrophobicity (the tendency to repel water) based on five independent numerical values. Advisor: Kamlakar Rajurkar

The inherent chemical, mechanical, and structural properties of nucleic acids make them ideal candidates for the formulation of tunable, personalized drug nanocarriers. However, none so far have exploited these properties for the controlled release of therapeutic drugs. In this dissertation, a biomimetic approach to controlling drug release is exhibited by specifically manipulating the architecture of novel, DNA nanoparticles to take advantage of drug binding mechanisms of action. Rationally designed DNA strands were immobilized on gold surfaces via a terminal thiol modification. Immobilized monomers can be manipulated to form distinct monolayer architectures including flat, folded, coiled, or stretched structures. Increasing the rate of folding is shown to restrict the diffusion of a surface-bound drug while upright architectures released drug at a 2 - 10 fold rate, depending on sequence length - using this strategy an over four-week release of dexamethasone was achieved. Furthermore, the release of an intercalating drug is controlled by exploiting sequence-specific affinities of the drug toward DNA. Here, using a high-affinity sequence and increasing the strand length a near zero-order release of daunomycin was achieved for up to 12 days. With this work, it is shown for the first time that the mechanisms of drug binding to nucleic acids can be utilized to produce highly controlled drug release from gold-core nucleic acid nanoparticles. These results will have a profound impact on the future design of novel, therapeutic nanocarriers.

Polyamides are versatile polymers and includes naturally occurring macromolecules such as proteins as well as purely synthetic materials such as Nylon-3 and Nylon-6 polymers. While there are different ways to prepare polyamides, polyamide synthesis using anionic ring opening polymerization of lactams is the most widely used technique, due to the ease in preparation, excellent control in molecular weight and availability of wide variety of monomers. Our group reported the preparation of carbohydrate-based polyamides called poly-amido-saccharides (PASs) using anionic ring opening polymerization of sugar b-lactam monomers. The PASs reported so far includes glucose, galactose, altrose and maltose PASs, and functional PASs with n-octyl, carboxylate and amine functionalities. Sulfated or block poly-amido-saccharides on the other hand are unknown. In this thesis, I describe the synthesis of sulfated and block poly-amidosaccharides as well as evaluation of their biomedical applications. Naturally occurring sulfated polysaccharides play important roles in anticoagulation, lubrication of cartilage, and in developmental processes. New glucose-based non-regioselectively and regioselectively sulfated poly-amido-saccharides are prepared by the polymerization of protected glucose b-lactams, followed by post-polymerization modification reactions. All polymers are water soluble, non-cytotoxic, and adopt helical conformations. I evaluated the anticoagulant activity of the sulfated polymers using in vitro, ex vivo, and in vivo methods as well as determined the mechanism of anticoagulation by amidolytic activity inhibition assays. Additionally, I synthesized new block copolymers as block copolymers are used for various applications including latex paints and pressure sensitive adhesives. Specifically, carbohydrate-based amphiphilic polymers are of interest for drug delivery applications, due to favorable properties such as cytocompatibility, low immunogenicity, and longer circulation time. We prepared PAS-based amphiphilic block polymers with varied polymer length, hydrophobic to hydrophilic ratio, and stereochemistry of hydrophilic component. I characterized these amphiphilic polymers by NMR, IR, GPC, DSC, TGA and CD, and they self-assemble in water to form nanostructures as determined by DLS, SEM, and cryo-TEM, and are non-cytotoxic.

Biomimetic technology takes cues from nature’s elegant engineering and applies these principles to novel therapeutics. By endowing nanoparticle and microparticle scaffolds with complex, multivalent functionalities, biomimicry allows us to enhance the potency of drug molecules and vaccines without sacrificing patient safety. In particular, membrane coated nanoparticles, derived from native extracellular and cellular membranes present in nature, have demonstrated tremendous success treating and protecting against various diseases. The first chapter of this dissertation explores biomimicry and its applications in nanomedicine in the context of bacteria. The remaining chapters of this dissertation apply these design principles to disease states. Through novel biomimetic designs, dosage requirements for effective treatment and vaccination are significantly reduced. Chapter two focuses on the design, fabrication, and application of extracellular membrane coated nanoparticles to treat lung disease. By endowing anti-inflammatory nanoparticulate cores with lung-tropic breast cancer exosome membrane, lung inflammation can be successfully managed with a lower therapeutic dose. The third chapter of this dissertation is dedicated to biomimetic vaccination against anthrax utilizing a known anthrax virulence mechanism. Macrophage membrane cloaked nanoparticles containing a potent adjuvant are further functionalized with an anthrax toxin to enable antigen-adjuvant co-delivery and single, low-dose vaccine protection. Overall, the rational design principles presented in this dissertation serve as a framework to develop a wide range of highly efficient, low-dose biomimetic nanocarriers to address unmet clinical needs.

Cell membrane coating technology is a technique that strips plasma membrane from intact cells and faithfully endows the biological functionalities onto inanimate materials. For immune modulation, this elegant strategy enables an effortless approach to design and synthesize multivalent vaccines against a multitude of different diseases. In combination with the unique attributes of nanotechnology, cell membrane coating technology can drastically improve the efficacy and safety of conventional drug formulations. The first chapter of this dissertation will explore the advantages of nanoparticles and how those distinctive properties can be leveraged for the application of biomimetic nanovaccines for personalized therapies.The second part of this dissertation will focus on the design of cell membrane-coated nanovaccines fabricated with materials sourced from pathogens. Through this process, the immune system is trained directly against the infectious agents and can immediately identify the threat upon encounter. Examples of this vaccination approach for a parasite and a multidrug-resistant bacteria will be elaborated. Along the lines of pathogenic diseases, the third section of this dissertation will examine a toxin-detainment approach for antivirulence vaccination. Host cell membrane is utilized to capture and attenuate the toxicity of bacterial virulence factors before the entire package is safely introduce to the host for immune priming. Rather than eliciting immunity towards the actual bacteria, antivirulence vaccination improve patient outcomes by removing the tools pathogens exploit for survival. The last portion of the dissertation will switch over to therapeutic vaccines for cancer therapy. In the first half, leukemic cell membrane is employed to educate host immune system to recognize lingering malignant cells following chemotherapy. In the second half, a micromotor is utilized along with bacteria-derived outer membrane vesicles for the physical disruption of solid tumors. The immunostimulatory membrane vesicles help recruit local immune cells to process the destroyed tumor cells for downstream immune activation. Ultimately, a potent immune response personalized for the treated tumor type is induced. By harnessing the ideas in this dissertation as a framework, a plethora of novel vaccines can be easily developed with cell membrane coating technology to address other areas of unmet clinical needs.

Electroactive polymers (EAPs) continue to gain attention for their potential to offer unique and versatile solutions in the soft robotic and flexible electronic industries. Ionic Polymer-Metal Composites (IPMCs) are a class of ionic-type EAPs which can be configured as capacitor actuators with very low voltage requirements (≤ 5 V AC or DC). Their compact, portable, and lightweight properties, coupled with a biomimetic bending actuation response make them ideal for human-machine integrated technologies such as medical implants, active skins, and artificial muscles. The Nafion-based IPMC can be described as a layered composite capacitor containing an ionic polymer core, sandwiched between chemically plated electrodes comprising of a conductive medium. Although there are reported achievements utilizing IPMCs in actuator configurations, their hydration-related sensitivity inhibits practical application in industry and makes experimental research difficult. This research sought to overcome these challenges by applying a wide range of experimental analyses, combined with theoretical modeling comparisons, to quantitatively characterize practical and standout factors impacting the actuator’s feasibility. The specific objectives investigated in this work include: (1) modifications of experimental test arrangements for practical insight; (2) investigation of IPMC degree of saturation and exposure correlations in both liquid and vapor conditions, coupled with electrical monitoring; (3) consideration of electrical field bias intensity and application arrangements on actuation behavior; and, finally, (4) practical inspection of IPMC design features and investigation of coating and geometric modification solutions for biomimetic and biocompatible applications. Investigations resulted in the development and validation of two testing configurations (contact-based and hydration-controlled) which provided reliable and repeatable testing. These systems included electrical and hydration control and monitoring which led to the identification of electrical tracking as a means to estimate IPMC performance. Additionally, optimized operation conditions were identified with special focus on the IPMC actuator’s performance variability. This work uncovered that the material’s inconsistency is a large factor inhibiting this technology from practical application. Electrical and actuation response analyses focused on the influence of the environment and voltage intensity on IPMC behavior changes with special emphasis on voltages surrounding reported electrolysis ranges unique to IPMCs. Lastly, a decision-making procedure was developed to optimize IPMC fabrication for soft-robotic biomimetic biocompatible solutions. This included emphasis on electrode deposition and patterns with quality analysis; IPMC hydrophobic coating solutions to inhibit solvent exchange; and modification of the geometric properties. All of this has culminated in a more pragmatic perspective on the potential of this technology and an identified course of action which could lead to the production of viable real-world application configurations which capitalize on the capabilities of these material arrangements.

Abstract: The menisci are a pair of knee joint structures that are wedge-shaped in cross-section and semi-lunar in superior view. They play roles in force distribution that help maintain the health of the articular cartilage. In adults, the menisci can be divided into a fibrous, vascularized outer region and a fibrocartilaginous, avascular inner region. Being avascular, the inner regions cannot heal upon injury, which predisposes the knee to early osteoarthritis development. The principal biochemical constituents of meniscus fibrocartilage include type I collagen and hyaline cartilage-associated biochemicals type II collagen and aggrecan. Meniscus fibrocartilage is synthesized and maintained by cells known as meniscus fibrochondrocytes (MFCs), which exist natively in a hypoxic and mechanically-loaded environment. Meniscus tissue engineering (MTE) aims to generate cell-based meniscus replacements in vitro that slow or prevent osteoarthritis development after incidence of non-healing meniscus injuries. This is accomplished using a suitable combination of biomaterial scaffolds, cells, and growth signals. To this end, this thesis focuses on: i) development of biomimetic meniscus scaffolds; ii) investigating the MFC response to combined hypoxia and mechanical loading; and iii) identifying how this knowledge can be used to enhance fibrocartilage histogenesis in vitro. Chapters 1 and 2 introduced the research topic with a review of meniscus development, comparative anatomy, and hypoxia and mechanical loading in MTE. This review suggested that the fibrocartilaginous phenotype of the adult human inner meniscus is likely an adaptation to its hypoxic and mechanically-loaded environment. The first project (Chapter 3) described design and production of 3D printed biomimetic meniscus scaffolds. The second project (Chapter 4) presented an investigation of the simultaneous response of MFCs to combined hypoxia and supplementation of the growth factor TGF-β3 in high-density cell aggregates (pellets). These treatments had synergistic interactions that potently promoted fibrocartilage histogenesis. Chapter 5 extended this study to a larger-scale model with a porous type I collagen scaffold. Hypoxia had few effects in this scaffold, even when combined with mechanical loading (dynamic compression (DC)). Chapter 6 investigated the factorial effects of cell expansion, hypoxia, and culture time to identify more suitable static pre-culture conditions on the scaffold before treatment with hypoxia and mechanical loading. Cell expansion had few effects, but mechanical properties and the hypertrophic phenotype increased continually up to the latest measured time point (9 weeks). Hypoxia suppressed both the hypertrophic phenotype and mechanical property development. Based on these outcomes, Chapter 7 investigated an intermediate pre-culture period in normal oxygen levels prior to a short-term treatment with hypoxia and mechanical loading (DC) to identify their effects on transcriptome-wide gene expression. The immediate MFC response to the combined treatment supported fibrocartilage histogenesis in an additive rather than synergistic manner. Chapter 8 described a series of four follow-up studies that used a shortened pre-culture period of 3 weeks based on experiences in Chapter 7 prior to hypoxia and mechanical loading treatments. First, the treatments were extended to five days and to include additional types of daily mechanical loading: i) a novel DC regime combining displacement and load control, and ii) cyclic hydrostatic pressure. The original DC regime, used in Chapter 7, was most effective in gene regulation. RNA sequencing showed that the longer-term combined treatment also supported fibrocartilage histogenesis, especially in promoting the hyaline cartilage-like aspect of the inner meniscus phenotype. The second and third studies of Chapter 8 showed that the gene expression response to DC saturated after 5 minutes and increased in magnitude with higher applied strain. The last study considered a long-term treatment of mechano-hypoxia conditioning, applying continuous hypoxia with four daily incidents of DC. The outcomes included increased equilibrium dynamic modulus to levels that rival the native meniscus, although further experimentation is required. Chapter 9 summarized the work and suggested future research directions. This thesis has three main contributions: i) the design of biomimetic meniscus scaffolds that can be used for complete meniscus tissue engineering; ii) the knowledge that the gene expression response of MFCs to combined hypoxia and mechanical loading is, after up to five days, primarily additive; and iii) the early evidence that combined hypoxia and mechanical loading, “mechano-hypoxia conditioning,” can be a useful strategy to promote fibrocartilage histogenesis in vitro for MTE.

Human skin is a complex tissue, consisting of multiple layers, vascular networks, and various cell types to create a barrier against external environmental factors. Numerous 3D in vitro models, including the most widely used organotypic 3D skin models, have been created to mimic human skin. One of the primary complications to generate physiologically representative skin tissue is an inability to integrate vasculature in the system. In addition, most hydrogel models are made of collagen type I which is not thermally stable limiting their application in burn or hyperthermic studies without compromising ECM. Currently, there is no available human skin model employing keratin, a more thermally stable protein that is also naturally present in human skin. We demonstrated an ECM comprising collagen and keratin blend supported growth and proliferation of human dermal fibroblasts and breast cancer cells as 3D human in vitro models for healthy and cancerous tissues, respectively. In addition, the inclusion of keratin in our matrix improved thermal and mechanical properties of the hydrogel by increasing the melting temperature and storage modulus, respectively. Therefore, we were able to demonstrate that the developed matrix can be used for longer-term thermal studies investigating the effect of various thermal stresses (such as hyperthermia and burn injuries) on cells response. Further, we have shown that adding keratin to the skin model promoted differentiation of keratinocytes by upregulating differentiation markers and increasing lysosomal activity compared to the 100% collagen control models. Cellular barrier function was also improved with increased electrical resistance and decreased permeability coefficients in collagen-keratin blended samples. We were also able to show that the inclusion of a vessel and continuous flow in our vascularized human skin equivalent model created a well-developed stratum corneum and a thicker epidermal layer compared to a static transwell models, indicating the importance of vasculature contribution on keratinocyte differentiation. Lastly, we were able to employ our VHSE model for burn testing, with observable expression of necrotic and apoptotic markers indicating tissue damage. In conclusion, the work presented here shows development of a novel VHSE tissue model employing keratin and the relevant applications in future human skin testing

Nature has developed highly specific and efficient catalysts to synthesize complex organic compounds, such as sugars in the process of photosynthesis. Due to the efficiency of these reactions, considerable effort has been placed to develop reaction schemes that can replicate the complexity of catalysts and products found in nature. The success of producing these biomimetic systems often leads to an improved understanding of biological systems, which can loop back and translate into better engineering of catalysts, aiming for instance, for enhanced stability and reduced cost. The use of inorganic nanoparticles (NPs) for developing biomimetic catalytic systems presents a favorable choice due to their ability to combine the robustness of inorganic catalysts with selectivity similar to that of enzymes. Other structural and functional characteristics similar to those of proteins can also be attained. Advancement in the understanding of NP self-assembly mechanisms allowed us to engineer terminal superstructures, known as supraparticles (SPs). The formation of SPs is not limited to the self-organization of inorganic NPs. Hybrid assemblies, containing NPs and multiple proteins at the same time have been developed. All these superstructures can potentially display catalytic functionalities replicating those of enzymatic assemblies, improving catalytic properties compared with singular NPs constituents due to collective interactions. The primary focus of this dissertation is to fabricate biomimetic suprastructures and explore their potential as photocatalysts. By taking advantage of the fundamental electrostatic interactions within the system, NP properties were tuned to conveniently fabricate hierarchical structures that mimic the structural complexity and functionality of materials found in nature. Thereby, a variety of semiconductor synthesis and assembly methods were established, offering immense tunability in the overall shape and size of SPs. Due to the general nature of supraparticles, which can be defined as complexes composed of two or more subunits or constituents, the composition of NPs within the SP was controllable, offering an additional level of design flexibility. Several key components were considered necessary when engineering SPs for catalytic application, including, facile and cost-effective synthesis method, absorption range, dispersion stability, and structural tunability. Overall, SPs offer a convenient platform for engineering catalysts using different building blocks as functional modules, leading to the development of more specific and sophisticated assemblies capable of replicating multiple functions of biological nanoassemblies.

Nature abounds with examples of shape morphing systems where an entity either gradually grows into a complex 3-D shape pattern or rapidly morphs into a new configuration. Inspired by the shape shifting capabilities of biological systems, in this work we study the response of natural and synthetic morphing systems through a few examples. These include the in vitro adaptive contraction of a cardiac muscle cell inside a constraining hydrogel, inflation of architectured rubber membranes, and a shape morphing soft robot. Cardiac muscle cells (cardiomyocytes), have an intrinsic mechano-chemo-transduction (MCT) mechanism that enable them to automatically convert mechanical loads into biochemical signals to actively regulate their amplitude and speed of contraction. At the molecular level, this is attributed to the morphing of regulatory and motor proteins (actin and myosin filaments) to facilitate muscle contraction. The underlying MCT mechanisms, however, are unclear and currently under investigation. To help decipher these mechanisms, we develop a mathematical model, as a companion tool for the experimental in vitro Cell-in-Gel system of our collaborators, to analyze the time-dependent, 3-D strains and stresses within a cardiomyocyte contracting in a viscoelastic medium. The model utilizes the exact analytical solution of the viscoelastic Eshelby inclusion boundary value problem as an efficient computational tool to simulate the mechanical fields inside and outside the cardiomyocyte. In a second study, we investigate the inflation of shape morphing synthetic soft composites with architectured geometry and material properties. Such shape morphing systems could have desirable applications in space deployable systems where there is a growing demand for energy-efficient lightweight and low-cost structures. These structures possess an exceptionally high mechanical packaging efficiency and very small stowage volume, which makes them attractive candidates for space applications including antenna reflectors, solar arrays, inflatable rovers, re-entry equipment, and human habitats. In particular, we explore several feasible 3-D shapes that can be achieved through the inflation of an initially flat rubber membrane with nonuniform geometrical and material properties. Our rubber-based prototypes provide a convenient basis for conceptual scientific and design explorations in shape morphing inflatable structures. In a third study, we explore the idea of shape shifting in the design and fabrication of synthetic soft robots with active components. Motivated by the swimming mechanisms of jellyfish, we develop a novel concept for a soft biomimetic underwater robot that imitates the shape and kinematics of the typical animal. The robot swims by harnessing the buckling instability of its soft body to quickly morph from an initially flat into a deformed dome-shaped configuration, which generates the required thrust for underwater locomotion. Joule heating of an embedded pre-stretched shape memory alloy spring, serves as an artificial muscle for the robot to make this shape morphing possible. The proposed synthetic shape morphing system introduces a new idea in design of simple, compact, and biomimetic robots with smart artificial muscles.

Cardiovascular disease is the leading cause of death globally, mainly due to blood vessel occlusions resulting in tissue necrosis and ischaemic strokes. When pharmacological intervention and native vessel transplantation are not viable, synthetic vascular conduits have been used. However, they are prone to failure at small diameters (

Metal ions are ubiquitous in biology and aid in facilitating many enzymatic transformations. For instance, high–valent iron–oxido and –hydroxido species are proposed to be key intermediates in oxidative processes catalyzed by non-heme iron proteins. A subclass of these proteins contains bimetallic sites that house either FeFe or FeM cores. To investigate the properties of both mono- and bimetallic cores, the Borovik Lab has developed a symmetric tripodal ligand framework containing phosphinic amido groups ([poat]3–), which can stabilize high-valent metal centers, provide an auxiliary binding-site for a second metal ion, and contains a pendant arm that can provide hydrogen-bond stabilization as well as facilitate proton shuttling. The work presented in this dissertation describes my efforts to access high-valent homo-/heterobimetallic oxido and hydroxido species by a variety of synthetic routes.Chapter 1 provides an overview of bimetallic proteins, and efforts by chemists to synthetically model the structure and function of these active sites. Previous work performed in the Borovik Lab to approach these synthetic challenges is discussed.Chapter 2 explores the oxidation chemistry of the mononuclear complexes FeII– and FeIII–hydroxido complexes in the [poat]3– framework, which serve as important synthons in the stepwise assembly of subsequent bimetallic complexes. While previous members in the Borovik Lab have studied these complexes, the electrochemical properties of these compounds are reassessed in my effort to access high-valent Fe–hydroxido species.Chapters 3 and 4 introduce the synthesis and characterization of discrete heterobimetallic complexes, with an MII–OH–FeIII or MII–O–FeIV core (M = Zn, Cu, Ni). This stepwise assembly approach allows for the formation of dinuclear compounds in an unsymmetric framework. The Fe center is supported by the [poat]3– ligand, while MII is supported by an N-based macrocycle. These species are compared with bimetallic complexes in similar frameworks.Chapters 5 describes the preparation of a series of di-Fe compounds with an Fe–O–Fe or Fe–OH–Fe core. These complexes are housed within the same unsymmetric scaffold, and span across four oxidation levels, from FeIIFeII to FeIIIFeIV. This study illustrates the multifunctional nature of the [poat]3- framework, and provides useful insight into the thermodynamic parameters of proton and electron transfers in bimetallic systems. These findings have significant implications for di-Fe containing enzymes, such as ribonucleotide reductase and soluble methane monooxygenase.Using the synthetic strategies developed in the previous chapters, Chapters 6 and 7 describe the preparation and characterization of a library of FeMn and MnFe complexes to model their biological counterparts. Their structural, electrochemical, magnetic, and reactivity properties are discussed. An FeIII–O–MnIV species was trapped and studied spectroscopically, and its relevance to similar high valent FeMn active sites is biology is discussed.Chapter 8 discusses the observation of a rare high-spin CoIII center in a bimetallic system via different spectroscopic techniques. This is an unusual finding, as most six-coordinated CoIII complexes adopt a low-spin configuration due to significant ligand field stabilization. A series of CoFe and CoGa complexes were prepared to probe the factors for this phenomenon, including the P=O groups in [poat]3- being weak field ligands, and modulation of spin exchange interactions.

Cell membranes have been widely used to create biomimetic nanoparticlesfor targeted drug delivery and detoxification. However, intracellular organelle membranes have not been used for biomimetic nanoparticle coating thus far. In this study, outer mitochondrial membranes (OMM) were used to coat PLGA cores to create OMM-coated nanoparticles (OMM-NPs). The B-cell lymphoma-2 (Bcl-2) receptors specific to the OMM enabled targeted detoxification of ABT-263, an anticancer Bcl-2 inhibitor. The OMM-NPs successfully decreased cell death in vitro and decreased ABT-263 induced-thrombocytopenia in vivo. OMM membranes were also used to coat the surface of Field Effect Transistors (FETs) to make OMM-FETs. These devices were successfully able to distinguish between different concentrations of compounds with Bcl-2 affinity. This study demonstrates that organelle membranes can help extend the functionality of nanomaterials and their unique surface receptors make them useful in targeted drug detoxification and detection.

Membrane proteins are responsible for significant proportion of cellular functions and therefore, implicated in many diseases. For example, more than 60% of therapeutics to date target membrane proteins to alter cellular functions that lead to disease. Recent work has shown that the local membrane environment made up of specific lipids surrounding the protein may be critical in regulating their function. Over the past several decades, supported lipid bilayers (SLB) have emerged as a useful model membrane system to investigate these essential protein functions along with their lipid environment because they can be compatible with wide range of surface-based analytical techniques to quantitatively analyze the biological outcome. However, it is still challenging to capture membrane proteins in functional states along with the native components of the plasma membrane. In this thesis, I proposed a novel strategy to take native cell membrane vesicles budded directly from living cell plasma membranes as intermediates to incorporate the native lipids and proteins into SLB platforms, without suffering from the significant downsides of traditional detergent-based reconstitution. This strategy allows preservation of the complexity of the cell plasma membrane and retention of the natural protein structure and functionality. Another critical advance I introduced to this platform was integration of supporting surface that is a transparent, conductive polymeric material that not only supports the membrane to increase its robustness, but also is capable of reporting protein function as well. These polymeric materials can be tuned so their mechanical property mimics native tissues and these materials are biocompatible with cell membranes, while their cushioning ability mitigates the deleterious interaction from commonly used silica-based surfaces. Due to the merits of the conducting polymer, I developed a biomembrane-based organic electronic device combining the native lipid environment, functional membrane proteins, soft tissue like supporting surfaces, and an electroactive surface that acts as a sensor and reporter. Altogether, with such a device I have demonstrated a variety of biosensing applications including pathogen detection, antibiotic screening, ligand-receptor binding, lipid constituent detection, and, perhaps most significantly, ion channel monitoring. These ion channel receptors are important therapeutic targets for pain management, yet little is understood about how they actually work and furthermore, the role of the membrane in their functions. This new biosensing platform may prove to be a useful new approach for pharmaceutical screening and development, as well as basic science studies of ion channel regulation and biology.

Nitrogenases are the only known biological enzyme capable of catalyzing the transformation of dinitrogen (N₂) into ammonia (NH₃). The active site of nitrogenase is comprised of a double-cuboidal iron-sulfur cluster featuring an interstitial carbide as the shared vertex, three ‘belt’ sulfides bridging the cuboidal components, and either a homocitrate-bearing heterometal (Mo, V) or an Fe at one of the distal capping metal sites. Out of the three nitrogenases, the Mo-dependent variant demonstrates the highest activity for N₂ conversion. The active-site cofactor of Mo-dependent nitrogenase (FeMoco) was first isolated in 1977; however, after decades of kinetic, structural, and spectroscopic research, many questions surrounding the mechanism of substrate reduction and the electronic structure of reaction intermediates remain unanswered. In this regard, the synthetic modelling community has contributed significantly towards directing mechanistic discussions with N₂-reducing functional model compounds. Furthermore, structural model compounds have played a pivotal role in deciphering the structural and electronic properties of FeMoco, including the identification of the central carbide and assignment of metal-site valence and spin states. Despite this remarkable progress, a synthetic model featuring a paramagnetic iron cluster with sulfides, interstitial carbide, and heterometal Mo has yet to be reported. The work relayed in this dissertation outlines our efforts towards pursuing this synthetic goal. As such, we utilize a family of carbonyl-supported iron clusters — first reported in the 1960s — featuring iron-coordinated inorganic carbide. However, the highly symmetric packing structures have made heterometal-containing carbidocarbonyl iron clusters difficult to unambiguously characterize by X-ray crystallography. Moreover, the strongly π-acidic ligation sphere enforces low metal-valance states and overall diamagnetism, and ligand substitution of COs is difficult to control. Here, we demonstrate a strategy to disrupt the symmetry in molybdenum-containing heteroclusters to unambiguously characterize the Mo site in XRD. Additionally, CO→S ligand substitution is achieved with the utilization of electrophilic sulfur sources, leading to progressively higher oxidation state Fe sites. These synthetic approaches for heterometal incorporation and oxidative sulfur insertion will serve as fundamental stepping-stones towards future endeavors in utilizing and functionalizing carbidocarbonyl iron clusters as synthetic precursors and ultimately, in biomimetically modeling the nitrogenase active site cluster.

Functional and stimuli responsive materials are becoming more and more important as technology continues to develop. Many of these materials are based on polymers that contain specific functional moieties that give the bulk material the desired properties. An emerging class of materials known as metallopolymers have been shown to be useful in this area. Metallopolymers are comprised of a polymer backbone that has been modified with a metal binding moiety and coordinated to a metal ion. In some cases these metal ions act as a cross linking agent to form a supramolecular material. Our group has focused on strategically choosing the metal complex to achieve specific functionalities. Traditionally we have focused on creating photoresponsive materials and used this as a way to change the mechanical properties of the material. While we have success in this area this is just the surface of the capabilities of these metallopolymer materials. The projects detailed in this dissertation focus on trying to create biomimetic materials and new photoresponsive materials from these coordination materials. The biomimetic catalysis project studied mimics of the catechol oxidase enzyme and focused on comparing a metallopolymer analog and a small model complex. The two catalysts exhibited differences in reactivity and the factors leading to this were studied through a variety of methods. The photoresponsive materials were focused on leucoindigo containing poly(vinyl alcohol) hydrogels that exhibited photoresponsiveness. The project revealed that the photochemistry of leucoindigo was affected by the polymer and by the inclusion of various metal ions. The third and final project described in this work focusses on using newly affordable technology for chemical education purposes. Infrared thermography is becoming more accessible with the development of smartphone compatible devices. Chemistry students have long struggled with basic chemistry concepts that are key to learning more advanced processes. These new IR cameras give students the ability to visualize otherwise invisible evidence of chemical processes. While this is accurate there is not a lot of curriculum that has been developed to take advantage of this technology. The final chapter details our explorations into developing general chemistry laboratory modules.

Bioinspiration is an emerging field of study. It translates to the creation of products, devices, and processes by using materials and processes found in living nature. Economic impact of bioinspired materials and surfaces is significant, on the order of several hundred billion dollars per year worldwide. Along the same line, this PhD dissertation attempts on solving two problems using bioinspired solutions: 1) the water crisis and 2) gas bubbles movement.Fresh water sustains human life and is vital for human health. Water scarcity affects more than 40% of the global population and is projected to rise. Furthermore, various factors, including population growth and unsafe industrial practices, have put strain on “clean” water supply in many parts of the world, including the Americas. It is certain than the current supply of fresh water needs to be supplemented to meet future needs. Living nature provides many lessons for water source. It has evolved species, which can survive in the most arid regions of the world by water collection from fog and condensation in the night. Before the collected water evaporates, species have mechanisms to transport water for storage or consumption. In this dissertation, first, an overview of these mechanisms is presented. Then, based on these mechanisms, the work done on bioinspired water harvesters is presented. Based on the results, design and projections of water harvesting towers is also presented. Gas bubbles are of interest in natural and technological applications. These applications include biomedicine, food production, drag reduction, water treatment, oil removal and surface cleaning. On the contrary, gas bubbles may also have a deleterious effect. For example, the gas bubbles produced in oil could potentially cause corrosion of pipelines resulting in reduced equipment life and wasted resources. Therefore, the study of gas bubbles movement in terms of their formation, interaction with underlying surfaces, and their movement is important. It was found that movement of gas bubbles and water droplets are similar in a way. Therefore, in this dissertation, the previously learnt lessons from nature, were also used for the gas bubbles movement. The results from the bioinspired gas bubble movement are also discussed in this dissertation.

The main objective of this work is to give contribution in both additive manufacturing (AM) and tribometry derived from the application and study of materials available with the use of biomimetic designs. Additional contributions are determining what effects treatments for flooring surfaces may have on the dynamic coefficient of friction and the effects of these products on common surfaces. The validity of the proposed methodology for a proof of concept was demonstrated by comparing measured dynamic coefficient of friction for designs using standardized equipment and comparing these values to plantar skin tested using an accepted and standardized testing method that has been extensively researched and validated. Initial biomimetic designs and characteristics unique to each design were researched and compared. Eleven designs were selected to be fabricated, tested, and compared to select the most desirable applications for further investigation. Research into potential treatments commercially available for use was done to determine the efficacy of these products. Prototype sensor designs were selected and fabricated using direct light processing (DLP) technology. Examination of the measured values was done through an analysis of the variances in the response variable and comparisons using Fisher and Tukey pairwise comparison method. Future work recommendations are provided for further development and improvement of the topics presented in this thesis.

The specificity, efficiency, and broad-spectrum functionality of proteins make them desirable materials for use in a wide range of applications, including biosensors, biofuel cells, or drug delivery technologies. Capitalizing on proteins for these purposes often requires immobilizing proteins to inorganic surfaces, such as to an electrode for a biosensor or a substrate for heterogeneous catalysis. Successful immobilization of proteins requires the preservation of protein conformation and function in an environment completely different than the cell. Moreover, the stability of a biomolecule depends on the presence or absence of local water molecules in and around its structure. Despite this, conventional methods for characterizing biomolecules at inorganic surfaces do not give direct information about the amount of water at these interfaces and how that water affects biomolecule structure. Here, we have developed a strategy for protein immobilization intended to preserve native protein structure by creating a biomimetic surface that imitates a protein’s natural cellular environment, and subsequently determined how water affects the structure of these surfaces. Biomimetic surfaces were made by covalently tethering short, helical peptides to an alkyl thiol self-assembled monolayer (SAM) on a gold substrate. Our helical peptides are designed to have solution-facing surfaces that attract and immobilize proteins of interest to the surface through an electrostatic mechanism. In order to investigate the importance of water in the structure and function of these biomimetic surfaces, we measured the quantity of water within the peptide and SAM layers using neutron reflectometry (NR) with the Liquids Reflectometer at Oak Ridge National Laboratory. Prior to peptide functionalization, NR of SAMs detected significant water penetration into each SAM composition, ranging from 1.6 to 5.7 water molecules per alkyl thiol when SAMs were immersed. This was the first direct measurement of water inside alkyl thiol SAMs and demonstrated that water accesses defects, amorphous regions, interdomain boundaries, and heterogeneous domains inherent to even well-formed SAMs. After peptide functionalization, water was found in both the SAM and peptide layers. The quantity of water in the SAM was twice that measured prior to peptide functionalization, suggesting the peptide disrupted the close-packed structure of the underlying SAM. To create an atomistic understanding of the amount of water measured around the peptide, we compared our NR data to previously published molecular dynamics (MD) simulations of the same peptide on a hydrophobic SAM in water and found the two techniques agreed. Combining these results with the dimensions of the peptide measured both experimentally and with MD, we hypothesize that immersing the peptide functionalized surface in water compressed the peptide closer to the SAM relative to its structure in ambient air. The amount of water readily accessible to the peptide-SAM interface reported here is the first step in assessing the quantity of water accessible to full proteins covalently bound to similar surfaces. Furthermore, we aim to test our protein immobilization hypothesis with azurin, an electron transfer protein, creating the groundwork for future immobilization experiments.

Natural plant surfaces, such as lotus leaves, rice leaves, and rose petals, possess unique wetting properties. Lotus leaves contain hierarchic micro/nano-topographies with a waxy coating and exhibit isotropic and ultralow flow resistance. A water droplet can roll off the surfaces that are tilted at a small angle regardless of the tilting direction. Rose petals also own hierarchic micro/nano-topographies, but with larger characteristic dimensions. The petal surfaces possess a high water flow resistance and can pin small water droplets on the surfaces even if the surfaces are positioned vertically or upside down. On the other hand, the petal surfaces are superhydrophobic so that the droplets can move without leaving any residue. A rice leaf has linearly arranged micro/nanopapillae, which lead to anisotropic flow resistance that can move water droplets preferably along the alignment. In this dissertation, bioinspired smart surfaces are investigated to mimic the distinct wetting properties on natural plant surfaces. In-plane mechanical stretching of the smart surfaces can dynamically and repeatedly modulate the characteristic dimensions of the micro-wrinkles, and in turn switch the surface wetting properties. With proper hydrophobic treatment, the wetting properties of the smart surfaces can be switched between lotus-like and rose-like; or lotus-like and rice-like. The surface wetting states can also be changed from Cassie Baxter state to Wenzel state by mechanical straining. In order to validate the efficacy of the smart surfaces in biomedical applications, droplet-based open channel microfluidics, and strain activated drug release are established respectively. In particular, lossless droplet transfer, droplet splitting, and modulation of droplet mobility are demonstrated on the lotus-rose switchable smart surfaces. Dynamic modulation of wetting anisotropy is exhibited on the lotus-rice switchable smart surfaces. Mechanical strain activated stepwise drug release are established using the smart surfaces that switch wetting states from the Cassie Baxter state to the Wenzel state. In addition, the perspectives of future development are discussed to expand the potential applications of smart surfaces.This dissertation proposes a new type of hierarchic topographies and provides a solid technical basis for creating the next-generation bioinspired smart surface and validating the enormous potentials of such smart surfaces in biomedical applications.

Geckos are famous for the skill of switchable adhesion that they use to stick on various surface while keep their fingers super clean. In the dissertation, a unique mechanism was discovered to explain gecko self-cleaning phenomena. Using atomic force microscopy (AFM), we managed to compare the microparticle-substrate adhesion and the microparticle-seta adhesion with a single seta bonded to the AFM cantilever. A dynamic effect was approved that high pulling-off speed could increase the microparticle-substrate adhesion and thus the self-cleaning appears at high moving speed. Based on the self-cleaning theory, a gecko-inspired N-doped graphene surface with switchable adhesion was achieved, which was designed into a bio-inspired micromanipulator with a success rate over 90%. When electrical bias was applied on this biomimetic surface, the charge concentration induced an electrical double layer (ELD) on the convex surfaces, which attracts polar water molecules to form a water bridge on it, significantly enhancing the adhesion on the wrinkled graphene surface, mimicking the capillary force on beetle feet. Therefore, the bio-inspired adhesive surface can be controlled with speed, electrical bias, humidity and different material surfaces. The water attraction phenomenon on the polarized surface was further tested for the potential application of water collection and evaporation in microsystems.

This thesis represents three major efforts in applying microscale additive manufacturing to address bioengineering applications. Additive manufacturing entails using basic building blocks to construct the three-dimensional structure of a device, affording rapid prototyping and lower costs in research and development. Here, a digital light processor (DLP) based stereolithography 3D printing system is leveraged to achieve microscale resolutions for devices. The first application creates microelectromechanical systems (MEMS) geometries for biosensors and biomimetic optics. The second application is to realize an integrated micro Tesla (µTesla) pump in a microfluidic platform. The third application is to optimize the fluid-surface coupling in the µTesla rotors to pump differential viscosities, including shear-thinning viscosities. These efforts span across Biosensors, Biomicrofluidics, and Biotransport and demonstrate 3D printing as a key enabling technology to improve bioengineering instrumentation. In the first part, MEMS interface with biology to create simplistic models of complex natural phenomena. In this work, 3D printing is used to create a microscale fabrication platform for carbon nanotube (CNT) proliferation. In a parallel work, the 3D printing aids in defining microoptic dimensions of a biomimetic compound eye element previously unattainable via traditional fabrication. In the second part, studies of biological phenomena can be augmented by microfluidic devices to model native physiological conditions at the microscale level. When studying the effect of shear stress and transport on beta cells in diabetes mechanisms, the need for an integrated, microscale flow source arose. This work introduces the µTesla pump as a flow source for lab-on-a-chip (LOC) applications. The experimental results demonstrate the µTesla pump’s capacity to generate highly controllable shear stress. Moreover, this work demonstrates the ability to fine-tune 3D printed surface characteristics to optimize pressure output of the system. Lastly, the pump’s capability to pump blood analog fluids is analyzed. Pumping of shear thinning fluid is investigated. This portion of the thesis aims to define the parameters of biofluids both from device perspective as well as pathophysiological perspectives through experimentation and modeling. Understanding gained in this thesis should help to model blood shear at the capillary level, a model for a number of diabetes and cardiovascular related diseases.

The mussel byssus is a collection of extra-organismal, acellular, proteinaceous load bearing structures that are radial displayed and utilized by marine mussels to secure themselves to a multitude of substrates. A single byssal thread can be subdivided into the loading bearing thread and adhesive plaque, which provide tensile strength and adhesive strength respectively. Both regions of the byssus face their own unique challenges and have devised independent mechanisms to protect themselves against oxidative stresses. Here we present evidence the mussel utilizes isolated redox compartments to protect 3, 4-dihydroxyphenylalanine (Dopa) from oxidative damage in both the thread and plaque, permitting long lasting mechanical performance of the byssus. The byssus thread is an extremely tough core-shelled fiber that dissipates substantial amounts of energy during tensile loading. The mechanical performance of the shell is critically reliant on Dopa’s ability to form reversible iron-catecholate complexes at pH 8. However, the formation of these coordinate crosslinks is undercut by Dopa’s oxidation to Dopa-quinone, a spontaneous process at seawater conditions. Using a combination of electron and atomic force microscopy we identify a previously undescribed stratum situated between the core and shell. Spectroscopy results indicate this region is rich in thiol and thus will be called the thiol rich layer (TRL). We propose the TRL acts as an electron sink to protect the shell against oxidation. Additionally, indentation type atomic force microscopy reveals the TRL has intermediate mechanical properties which act as a mechanical buffer between the shell and core. The adhesive plaque is also reliant on Dopa. Dopa in the plaque is primarily responsible for strong adhesion but only if protected from oxidation at the adhesive-substratum interface. Dopa oxidation is thermodynamically favorable in seawater yet barely detectable in mature plaques. Experiments were designed to understand how plaques insulate Dopa-containing mfps against oxidation. Spectrometry and confocal fluorescence results indicate seawater sulfate triggers a mfp3 and mfp6 liquid-liquid phase separation (LLPS). Subsequently, cyclic voltammetry of LLPS material demonstrates DOPA’s redox potential is phase dependent. Furthermore, mass spectrometry and redox exchange assays indicate Dopa-containing mfp-3 and mfp-6 in phase-separated droplets remain stable despite rapid oxidation in the equilibrium solution. Taken together, the results suggest that a cohort of oxidation-prone proteins is endowed with phase-dependent redox stability. Moreover, in forming LLPS compartments, Dopa-proteins become reservoirs of chemical energy which can be called upon in the event of oxidative damage.

The need for a detailed mechanistic understanding of the photoisomerization of retinal chromophore (retinal protonated Schiff base, rPSB) is becoming increasingly important, not only due to its fundamental importance in vision but also owing to the growing number of applications in various fields. The development of microbial rhodopsin based fluorescent probes and actuators essential in neuroscience, synthetic bio-mimetic molecular switches and motors useful in material science and synthetic biology are examples of such applications. The work presented in this dissertation is devoted to unveil and understand a novel mechanistic factor with significant impact on the photoisomerization of rPSB-like systems. This factor corresponds to the interaction between the first electronic excited state and higher states (usually the second excited state) occurring during the excited state lifetime or, in other words, along the excited state photoisomerization coordinate. This "electronic state mixing" effect is studied by employing different computer tools including hybrid quantum mechanics/molecular mechanics (QM/MM) methods. The investigated systems include representative animal and microbial rhodopsins, bio-mimetic N-alkyl-indanylidene-pyrrolinium (NAIP) molecular switches and a recently reported water soluble rhodopsin mimic. Our results unveil two type of effects due to changes in the electronic mixing: an impact on the excited state lifetime and an impact on vibrational coherence as we now briefly describe.The impact on excited state lifetime is first demonstrated by uncovering the variation of rPSB photoisomerization speed in different environments is due to an increase or decrease of electronic state mixing and that this effect can be controlled by the electrostatic field of the environment. This leads us to hypothesize that animal rhodopsins, which isomerize within 200 fs, have been evolved to minimize the electronic state mixing such that biological functions are carried out in a timely manner. We then show that electronic state mixing can be used as a design principle to achieve artificial rPSBs with a longer excited state lifetime useful for producing rhodopsin based fluorescent probes. In this context, we demonstrate that minor electron donating or withdrawing chemical substitutions can cause an increase or decrease in the photoisomerization speed of rPSB. We have also investigated the photocycle and the electronic state mixing of a water-soluble artificial rhodopsin mimic. The room temperature photodynamics simulations of this system suggests that molecules of a light excited population which decay early or later is possibly modulated by electronic state mixing.The impact of electronic state mixing on vibrational coherence is mainly investigated focusing on synthetic molecular switches. Accordingly, we show how electronic state mixing induced by steric effects can be used to control the vibrational coherence of NAIP molecular switches. On this basis, we propose that vibrational coherence may be engineered into other synthetic molecular devices by modulating steric and electronic effects.

Mono-iron hydrogenase is one of three types of hydrogenases, catalyzing reversible hydride transfer to the substrate (methenyl-H₄MPT⁺) by heterolytically cleaving molecular hydrogen into a proton and a hydride. The key features of the enzyme’s active site include a pyridone moiety, an acyl unit and facial ligation of C [superscript acyl] N [superscript pyridone] S [superscript Cys] donors. Each feature was independently incorporated into a selected ligand system (Schiff-base N4, pincer and thianthrene scaffold, respectively), in efforts to i) develop possible bioinspired catalysts for H₂ activation using earth abundant metals (iron, cobalt, manganese) and ii) make synthetic models of the enzyme active site for deeper understanding of the architecture of the active site and catalytic mechanism. Synthetic routes for making pyridone-based Schiff-base N4 and NNS type ligands were explored: although not isolated, the ligands were spectroscopically detected. On the other hand, the simpler version—pyridine-based Schiff-base N4 ligands—afforded dinuclear cobalt complexes upon metalations with cobalt(II) precursors. Depending on the length of the diamine-linker as well as the substituents on the pyridine rings, either spontaneous O₂ activation or B–F activation was observed, yielding μ-peroxo dicobalt(III) complexes or μ-fluoride bridged dicobalt(II) complexes, respectively. In particular, two μ-fluoride bridged dicobalt complexes showed antiferromagnetic coupling between the two cobalt(II) centers. From the pincer ligands featuring the unique acyl moiety within C [superscript acyl] N [superscript pyridine] S [superscript thioehter] and C [superscript acyl] N [superscript pyridine] P [superscript Ph2] donor set, the (expected) meridional and an (unexpected) facial iron-acyl complexes were isolated, respectively. Upon deprotonation (pyridine→pyridinate de-aromatization), both complexes showed reactivity towards H₂ activation; no evidence for hydride-transfer was observed. For the facial ligation, thianthrene-scaffolded manganese system was examined as a more flexible version of the anthracene-scaffolded systems. Preliminary results of the kinetic studies support the correlation between the flexibility of the scaffold and the reactivity of the metal complex, without greatly altering the electronic environment of the metal center.

Retinal vascular inflammation is a common characteristic of diabetes. It is marked by upregulation of a major retinal endothelial cell adhesion molecule ICAM-1 that promotes leukocyte-endothelial adhesion. The adherent leukocytes subsequently release cytotoxic, hyperpermeability and pro-inflammatory factors to cause extensive vascular damage in the retina that often lead to diabetic retinopathy (DR), a vision-threatening condition that affects nearly 40% of all people with diabetes. Past studies have identified retinal endothelial ICAM-1 expression as a rate-limiting step in DR pathogenesis because inhibiting it blocked DR progression in vivo. A common anti-ICAM-1 therapy for DR involves the use of salicylates that block activation of NF-KB, a major transcription factor required for ICAM-1 upregulation. However, the clinically-used high levels of salicylates cause severe adverse off-target effects in the body. To address this major limitation, thiswork describes the use of biomimetic nanoparticles (NPs) that selectively deliver salicylate to ICAM-1-expressing retinal endothelial cells (ECs) and blocks leukocyte-EC adhesion. Specifically, these biomimetic NPs are derived from red blood cell membranes, surface modified with an ICAM-1-targeting single chain variable fragment (scFv), and loaded with sodium salicylate. Detailed physicochemical characterization revealed that these NPs are ~16035 nm in diameter, successfully conjugate anti-ICAM-1 scFv on their surface, and exhibit ~45% drug incorporation. Importantly, in vitro studies show that these drug-loaded NPs undergo preferential (~2-fold greater) uptake in ICAM-1-expressing retinal ECs and, crucially, exhibit a remarkable 700-fold greater efficacy of sodium salicylate in blocking leukocyte-EC adhesion. These promising findings lay the foundation for more detailed assessment of this anti-inflammatory nanotherapeutic as a new and improved treatment strategy for DR.

The ever increasing demand for global travel coupled with increasing costs of fuels have prompted many researchers to study new methods to save fuel to make travel more efficient. One of the proverbial low-hanging fruits for fuel efficiency is aerodynamic drag reduction. Simple changes in the shape or placement of structures on the surface of different types of vehicles have been shown to increase fuel efficiency by reducing drag (e.g., add-on lower and aft wake fairings on tractor trailers which have seen a tremendous rise in popularity on US highways in recent years). Areas of interest in drag reduction have typically been in flow control of the boundary layer. Flow control techniques include both passive and active methods. Passive methods include biomimetic structures, riblets, and vortex generators. Active control techniques that are zero mass injection include dielectric barrier discharge (DBD) techniques, dynamic roughness (DR) employed by actively moving specific parts of the skin on the aerodynamic surface, or methods as simple as vibrating the entire surface. Biomimetic micro and macro structures were investigated in these experiments to determine their efficacy as methods of aerodynamic drag reduction. Wind tunnel experiments were conducted to determine the viscous drag on a flat plate covered with several different micro- and macro surface treatments. The biomimetic surface treatment structures use various geometric forms cast in Sylgard-170 and applied to a smooth, flat, glass substrate. The near-wall boundary layer velocity profiles were determined using planar particle image velocimetry (PIV), a method which utilizes a particle-seeded flow and a pulsed laser illumination and a camera system to capture and cross-correlate the flow field within the region of interest to statistically determine its 2D flow field velocity vectors. Four different Reynolds numbers with varying degrees of free stream turbulence were tested, as well as passive and active vibration modes for all of the surface treatment test articles. Post processing analysis of the flow field within the boundary layer of each model was performed, including determination of the shear stress at the wall of each boundary layer, as well as numeric integration of the velocity profiles for a direct momentum analysis. Boundary layer shape factors were calculated to help determine the likelihood of local flow separation related to viscous drag. Results indicated that the tested biomimetic micro- and macro surface structures can provide some drag reduction in both passive and active flow control modes in both laminar and turbulent flow at low Reynolds numbers O(104). With improved scaling of the casting size, biomimetic micro- and macro structures could potentially be an effective form of drag reduction for many different aerodynamic applications.

Both bird and fish locomotion are thought to be more efficient than the equivalent man-made vehicles driven by propellers/impellers and jet engines. Through studies that decompose the different kinematic and shape effects of these biological systems, we can understand what leads to their high cruising performance and efficiency. Two major studies were conducted. The first was on the effect of different kinematic parameters of large soaring birds on flight performance and the second was on the effect of caudal fin shape on the performance of thunniform swimmers. For the first study on flight performance, flapping, folding, and twist were the wing motions of interest. The second study on swimming performance observed how caudal fin sweep angle affects propulsion while isolating the effect of this shape difference from aspect ratio and area effects. Low order models were primarily used to conduct the bird flight study, though experimental methods were investigated as well. The thunniform swimming study was conducted through experimentation on a biomimetic system. The flight study found that, under the right circumstances, both wing twist and wing folding have a positive effect on flight performance. However, the impact of wing twist is much larger. To incorporate this wing twist into a robotic system, a new reduced order model that partially accounts for 3D effects was developed and validated. In the future, this model can be used in conjunction with a flight controller to control wing twist. The swimming study found that caudal fin sweep had a significant impact on performance, moderately swept fins showing the greatest improvement. Using an overly large sweep angle led to diminished performance when compared to the moderately swept fins, but still demonstrated improved performance over a non-swept fin. The increased performance of the moderately swept fins was due to how it affected LEV formation and stability.

Research on bacteria in their biofilm form is limited by the ability to artificially culture bacterial biofilms in a system that permits the visualization of individual cells. The experiments comprising this thesis research are on-going investigations of bacterial culture systems engineered to provide an environment that mimics biofilms while enabling real-time microscopy. Specifically, the microfluidic systems developed and assessed as part of this thesis permit the visualization of individual bacteria cells within consortia growing within a narrow space provided by a microfluidic device. This research demonstrates the versatility of these microfluidic systems across potentially high-throughput microbiological experiments utilizing genetically engineered Escherichia coli. Before demonstrating the efficacy of these systems, the development of the field of synthetic biology over the past half century is reviewed, focusing on synthetic genetic circuits and their applications (Chapter 2). The first and main microfluidic device explored in this research was developed to mimic the nutrient-deficient conditions within biofilms by forcing media to enter the culture area through a narrow, torturous channel. The microfluidic channel was thin enough (0.97 μm) to prevent the motility of 1-μm-wide E. coli cells, enabling visualization of individual cells. The bacteria cultured in the device contained either a simple Plux-driven quorum sensing receiver (Chapters 3 and 5) or a LacI- and TetR-driven genetic toggle switch (Chapter 4). Under the culture conditions, the quorum sensing reporter signal was detected even without addition of the signaling molecule (Chapter 3). The genetic toggle switch was stable when the system began in the high-LacI expression state, but after 5 days of culture, >5% of high-TetR expression cells began to consistently express the high-LacI state (Chapter 4). This system was also employed to track lineages of cells using real-time microscopy, which successfully characterized the inheritance of aberrant, enlarged cell phenotypes under stress (Chapter 5). Another microfluidic device, a droplet bioreactor, was also developed to culture small numbers of cells in an aqueous bubble suspended in oil (Chapter 6). Quorum sensing receiver cellswere cultured in this device, demonstrating that it is well suited for testing the effects of compounds on biofilms within water-in-oil droplets.

The purpose of this study is to build and test a pneumatically actuated robot based on the biomimetic design of a seahorse tail. McKibben muscles, a form of pneumatic actuator, have been previously used to create highly flexible robots. It has also been discovered that the seahorse tail serves as a highly flexible and prehensile, yet armored appendage. Combining these topics, this research aims to create a robot with the mechanical flexibility of a pneumatic actuator and the protection of a seahorse tail. First, the performance of a miniature McKibben muscle design is examined. Then, the artificial muscles are implemented into a 3D-printed seahorse tail-inspired skeleton. The robot's actuation was observed to determine its maximum bending capacities. The results of the experiments revealed that the miniature McKibben muscles performed comparably to larger sized McKibben muscles previously reported in literature. The pneumatically actuated robot achieved a maximum bend angle of ~22°. Further research is recommended to determine the behaviors of similar robots with additional plates or McKibben muscles spanning shorter plate sequences.

Across species, bats exhibit wildly disparate differences in their noseleaf and pinnae shapes. Within Rhinolophid and Hipposiderid families, bats actively deform their pinnae and noseleaf during biosonar operation. Both the pinnae and noseleaf act as acoustic baffles which interact with the outgoing and incoming sound; thus, they form an important interface between the bat and its environment. Beampatterns describe this interface as joint time-frequency transfer functions which vary across spatial direction. This dissertation considers bat biosonar shape diversity and shape dynamics manifest as beampatterns. In the first part, the seemingly disparate set of functional properties resulting from diverse pinnae and noseleaf shape adaptations are considered. The question posed in this part is as follows: (i) what are the common properties between species beampatterns? and (ii) how are beampatterns aligned to a common direction for meaningful analysis? Hence, a quantitative interspecific analysis of the beampattern biodiversity was taken wherein: (i) unit[267]{} different pinnae and noseleaf beampatterns were rotationally aligned to a common direction and (ii) decomposed using principal component analysis, PCA. The first three principal components termed eigenbeams affect beamwidth around the single lobe, symmetric mean beampattern. Dynamic shape adaptations to the pinnae and noseleaf of the greater horseshoe bat (textit{Rhinolophus ferrumequinum}) are also considered. However, the underlying dynamic sensing principles in use are not clear. Hence, this work developed a biomimetic substrate to explore the emission and reception dynamics of the horseshoe bat as a sonar device. The question posed in this part was as follows: how do local features on the noseleaf and pinnae interact individually and when combined together to generate peak dynamic change to the incoming sonar information? Flexible noseleaf and pinnae baffles with different combinations of local shape features were developed. These baffles were then mounted to platforms to biomimetically actuate the noseleaf and pinnae during pulse emission and reception. Motions of the baffle surfaces were synchronized to the incoming and outgoing sonar waveform, and the time-frequency properties of the emission and reception baffles were characterized across spatial direction. Different feature combinations of the noseleaf and pinnae local shape features were ranked for overall dynamic effect.

The design and synthesis of multicomponent Pt-based nanomaterials with highly controlled structures have attracted extensive research attention, mainly due to their highly active catalytic properties. The performance enhancement of these catalytic systems largely requires the precise control over the structure with the lowest Pt amount yet high activity to mitigate the high cost of Pt-based nanomaterials. Specific surfactant molecules have been widely employed to manipulate the morphologies and assemblies of nanostructures. Thus rational designs of the surfactants become very significant. In nature, a lot of biomaterials evolved well-developed nanostructures with unique properties through long-time natural selection using biomolecules as the surfactant. Compared with traditional trial-and-error design, biomimetic design provides more rational controls leading to new synthetic design for nanostructures. In this thesis, synthesis and assembly of Pt-based nanocrystals and the mechanisms were studied. Chapter 2 introduces one-step synthesis of single-crystal PtNi octahedron with in situ developed highly concave feature and self-confined composition was studied which is optimal for oxygen reduction reaction (ORR). The combination of Ni facet segregation and oxygen etching of Ni-rich surface lead to the concave feature and confined Ni content. The concave PtNi nanocrystal exhibited a very high activity as well as a remarkable stability in ORR. Chapter 3-4 explores biomimetic approaches to achieve functional Pt nanostructures and their hierarchical assembly. In Chapter 3 a rational designed peptide was utilized to prepare an ultrathin Pt multiple-twinned nanowire network (MTNN) as an efficient electrocatalyst. In Chapter 4 we further demonstrate a biomimetic approach to explore the impact of higher order structures of surfactants on NC formation and alignment. Results show that at low concentration T7 peptide molecules (Ac-TLTTLTN-CONH2) form ST-turns and benefit the selective formation of cubic Pt NCs, and that β-sheets favored under high concentration readily promote linear self-assembly of the cubic NCs along [100] direction. Tailoring the formation conditions of the secondary structures of biomolecules can realize better tuning of peptide concentration controlled NC behaviors via a process that is analogous to biological regulations in organisms. Great potential in regulating in vivo performance of non-biological substances and derived applications become possible.