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Rapid adoption of battery electric vehicles means improving energy consumption is a top priority. Regenerative braking converts kinetic energy to electrical energy stored in the battery pack while the vehicle is decelerating. Coasting is an alternative strategy that minimizes energy consumption by decelerating the vehicle using only road load. This work refines a battery electric vehicle model to assess regen, coasting, and other deceleration strategies. A road load model based on public test data calculates tractive effort based on speed and acceleration. Bidirectional Willans lines are the basis of the powertrain model simulating battery energy consumption. Regen braking tractive and powertrain power are modeled backward from prescribed linear velocity curves, and the coasting trajectory is forward modeled given zero tractive power. Decel modes based on zero battery and motor power are also forward modeled. Multi-Mode decel (using a low power mode with regen) is presented as an intermediate strategy. An example vehicle is modeled in fixed-route simulations using these strategies and is scored based on travel time, energy consumption, and bias towards minimizing one of those metrics. Regen braking has the lowest travel time, and coasting the lowest energy consumption, but such bias increases overall cost. Multi-mode strategies lower overall cost by balancing reductions in travel time and energy consumption. The model is sensitive to grade and accessory load fluctuation, making this work adaptable to different vehicles and environments. This work demonstrates the utility of regen braking alternatives that could enhance connected and automated vehicle systems in battery electric vehicles. / Master of Science / As battery electric vehicle adoption accelerates, reducing energy consumption remains a priority. While regenerative braking saves energy by recharging the battery pack using kinetic energy, coasting (deceleration caused only by road load) has potential as well. This work focuses on refining a battery electric vehicle model and assessing various deceleration strategies. A road load model calculates wheel tractive effort, and Willans lines are used to model powertrain energy consumption. Coasting and other deceleration modes based on zero system power are modeled to produce speed trajectories, and regenerative braking power is modeled using prescribed linear velocity curves. Strategies that use multiple decel modes are also considered. An example battery electric vehicle is assessed using these strategies in fixed-route simulations. Vehicle performance is scored based on battery energy consumption and travel time. Regenerative braking has the lowest travel time, and coasting the lowest energy consumption, but those strategies also have the highest overall cost. Multi-mode strategies lower cost by balancing energy consumption and travel time. The strategies are sensitive to changes in road grade and accessory power, meaning the model can be used with different vehicles and environments. This work demonstrates the utility of alternatives to regenerative braking and how such strategies could enhance battery electric vehicles with autonomous capabilities.

A novel technique is investigated for utilizing the motion caused by environmental forces on a civil structure to generate electrical energy when the structure's response is within safety limits. When strong winds and earthquakes occur, the utility power source which supply energy to the actuator in an active control system is usually not reliable. With a regenerative electric actuator, recovered energy can be used to reduce the peak oscillations of the structure by applying forces (through actuators which use the recovered energy) counter to the environmental forces even if the utility power is not available. The use of a regenerative electric actuator allows a precise control of the amount of damping being provided by the actuator. Another advantage of using regenerative electric actuators is the reduction of the required energy capacity of the electrical source. This translates into lower energy ratings for the electrical source, and lower equipment and maintenance costs. This study is the first of its kind to propose and investigate active control of civil structures using regenerative electric actuators. This study is also the first of its kind to investigate the applicability of sliding mode control to civil structures using regenerative electric actuators. Sliding mode control provides a natural synthesis of the on-off nature of pulse width modulation control and control force saturation, and guarantees stability for the control law. It is also invariant to parameter changes and external disturbances. New direct-control schemes for neural network and adaptive fuzzy control of civil structures using regenerative electric actuators are proposed and investigated. These allow on-line control of the structure without the need for either an accurate model of the system or a specific learning stage. Since the error at the output of these controllers will be unknown in the direct-control scheme, the error at the system output is used to train or update the controller parameters. Simulations are conducted for wind and earthquake excitations using linear and nonlinear models. It is shown that the use of regenerative electric actuators is a viable and a reliable alternative for active control of civil structures. / Ph. D.

Tendon function is essential for quality of life, yet the pathogenesis and healing of tendinopathy remains poorly understood compared to other musculoskeletal disorders. The aim of regenerative medicine is to replace traditional tissue and organ transplantation by harnessing the developmental potential of stem cells to restore structure and function to damaged tissues. The recently discovered interdependency of cell phenotype and biophysical environment has created a paradigm shift in cell biology. This dissertation introduces a dynamic in vitro model for tendon function, dysfunction and development, engineered to characterize the mechanobiological relationships dictating stem cell fate decisions so that they may be therapeutically exploited for tendon healing. Cells respond to mechanical deformation via a complex set of behaviors involving force-sensitive membrane receptor activity, changes in cytoskeletal contractility and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell-matrix forces with high fidelity. A naturally-derived decellularized tendon scaffold (DTS) was invented to serve as a biomimetic tissue culture platform, preserving the structure and function of native extracellular matrix. DTS in concert with a newly designed dynamic mechanical strain system comprises a tendon bioreactor that is able to emulate the three-dimensional topography, extracellular matrix proteins, and mechanical strain that cells would experience in vivo. Mesenchymal stem cells seeded on decellularized tendon scaffolds subject to cyclic mechanical deformation developed strain-dependent alterations in phenotype and measurably improved tissue mechanical properties. The relative tenogenic efficacies of adult stem cells derived from bone marrow, adipose and tendon were then compared in this system, revealing characteristics suggesting tendon-derived mesenchymal stem cells are predisposed to differentiate toward tendon better than other cell sources in this model. The results of the described experiments have demonstrated that adult mesenchymal stem cells are responsive to mechanical stimulation and, while exhibiting heterogeneity based on donor tissue, are broadly capable of tenocytic differentiation and tissue neogenesis in response to specific ultrastructural and biomechanical cues. This knowledge of cellular mechanotransduction has direct clinical implications for how we treat, rehabilitate and engineer tendon after injury. / Ph. D.

Vat photopolymerization (VP) is an additive manufacturing (AM) technology that permits the fabrication of parts with complex geometries and feature sizes as small as a few microns. These attributes make VP an attractive option for the fabrication of scaffolds for tissue engineering. However, there are few printable materials with low cytotoxicity that encourage cellular adhesion. In addition, these resins are not readily available and must be synthesized. A novel resin based on 2-acrylamido-2-methyl-1-propanesulfonic acid (NaAMPS) and poly(ethylene glycol) diacrylate (PEGDA) was formulated and printed using VP. The mechanical properties, water content, and high fidelity of the scaffold indicated promise for use in tissue engineering applications. Murine fibroblasts were observed to successfully adhere and proliferate on the scaffolds. The growth, migration, and differentiation of a cell is known to dependent heavily on its microenvironment. In engineered constructs, much of this microenvironment is provided by the tissue scaffold. The physical environment results from the scaffold's geometrical features, including pore shape and size, porosity, and overall dimensions. Each of these parameters are known to affect cell viability and proliferation, but due to the difficulty of isolating each parameter when using scaffold fabrication techniques such as porogen leaching and gas foaming, conflicting results have been reported. Scaffolds with pore sizes ranging from 200 to 600 μm were fabricated and seeded with murine fibroblasts. Other geometric parameters (e.g., pore shape) remained consistent between scaffold designs. Inhomogeneous cell distributions and fewer total cells were observed in scaffolds with smaller pore sizes (200-400 μm). Scaffolds with larger pores had higher cell densities that were homogeneously distributed. These data suggest that tissue scaffolds intended to promote fibroblast proliferation should be designed to have pore at least 500 μm in diameter. Techniques developed for selective placement of dissimilar materials within a single VP scaffold enabled spatial control over cellular adhesion and proliferation. The multi-material scaffolds were fabricated using an unmodified and commercially available VP system. The material preferences of murine fibroblasts which resulted in their inhomogeneous distribution within multi-material scaffolds were confirmed with multiple resins and geometries. These results suggest that multi-material tissue scaffolds fabricated with VP could enable multiscale organization of cells and material into engineered constructs that would mimic the function of native tissue. / Doctor of Philosophy / Vat photopolymerization (VP) is a 3D printing (or additive manufacturing) technology that is capable of fabricating parts with complex geometries with very high resolution. These features make VP an attractive option for the fabrication of scaffolds that have applications in tissue engineering. However, there are few printable materials that are biocompatible and allow cells attachment. In addition, those that have been reported cannot be obtained commercially and their synthesis requires substantial resources and expertise. A novel resin composition formulated from commercially available components was developed, characterized, and printed. Scaffolds were printed with high fidelity. The scaffolds had mechanical properties and water contents that suggested they might be suitable for use in tissue engineering. Fibroblast cells were seeded on the scaffolds and successfully adhered and proliferated on the scaffolds. The growth, migration, and differentiation of cells is influenced by the environmental stimuli they experience. In engineered constructs, the scaffold provides many of stimuli. The geometrical features of scaffolds, including how porous they are, the size and shape of their pores, and their overall size are known to affect cell growth. However, scaffolds that have a variety of pore sizes but identical pore shapes, porosities, and other geometric parameters cannot be fabricated with techniques such as porogen leaching and gas foaming. This has resulted in conflicting reports of optimal pore sizes. In this work, several scaffolds with identical pore shapes and porosities but pore sizes ranging from 200 μm to 600 μm were designed and printed using VP. After seeding with cells, scaffolds with large pores (500-600 μm) had a large number of evenly distributed cells while smaller pores resulted in fewer cells that were unevenly distributed. These results suggest that larger pore sizes are most beneficial for culturing fibroblasts. Multi-material tissue scaffolds were fabricated with VP by selectively photocuring two materials into a single part. The scaffolds, which were printed on an unmodified and commercially available VP system, were seeded with cells. The cells were observed to have attached and grown in much larger numbers in certain regions of the scaffolds which corresponded to regions built from a particular resin. By selectively patterning more than one material in the scaffold, cells could be directed towards certain regions and away from others. The ability to control the location of cells suggests that these printing techniques could be used to organize cells and materials in complex ways reminiscent of native tissue. The organization of these cells might then allow the engineered construct to mimic the function of a native tissue.

A vehicle has several rotating components such as a traction electric motor, the driveline, and the wheels and tires. The rotating inertia of these components is important in vehicle performance analyses. However, in many studies, the rotating inertias are typically lumped into an equivalent inertial mass to simplify the analysis, making it difficult to investigate the effect of those components and losses for vehicle energy use. In this study, a backward-tracking model from the wheels and tires to the power source (battery or fuel cell) is developed to estimate the effect of rotating inertias for each component during propulsion and regenerative braking of a vehicle. This paper presents the effect of rotating inertias on the power and energy for propulsion and regenerative braking for two-wheel drive (either front or rear) and all-wheel drive (AWD) cases. On-road driving and dynamometer tests are different since only one axle (two wheels) is rotating in the latter case, instead of two axles (four wheels). The differences between an on-road test and a dynamometer test are estimated using the developed model. The results show that the rotating inertias can contribute a significant fraction (8 -13 %) of the energy recovered during deceleration due to the relatively lower losses of rotating components compared to vehicle inertia, where a large fraction is dissipated in friction braking. In a dynamometer test, the amount of energy captured from available energy in wheel/tire assemblies is slightly less than that of the AWD case in on-road test. The total regenerative brake energy capture is significantly higher (> 70 %) for a FWD vehicle on a dynamometer compared to an on-road case. The rest of inertial energy is lost by inefficiencies in components, regenerative brake fraction, and friction braking on the un-driven axle. / Master of Science

The exponential growth of international tourism necessitates a shift towards more sustainable and holistic development strategies. This thesis explores the concept of regenerative tourism, focusing on Hawai’i - a popular tourist destination renowned for its natural beauty yet facing significant environmental and social impacts from tourism. This thesis explores the paradox of balancing the economic necessity of tourism while preserving local communities and the environment. This study aims to investigate the implementation of regenerative tourism in Hawai’i, focusing on its interaction with local communities to address environmental and social well-being. Through interviews with Native Hawaiians, local communities, tourism industry employees, and tourists, the study explores perceptions and collaborations within the tourism industry. The research employed the theoretical frameworks of Regenerative Development, Communities of Practice and Transformational Leadership to deepen the analysis of the current implementation and effectiveness of regenerative practices in Hawai’i.  Findings reveal that while there is an awareness of the need for inclusion in regenerative practices, increased efforts are necessary to include Indigenous voices and ensure economic sustainability for local communities. The recommendations of this study highlight the importance of respect, inclusion, and empowerment of Native Hawaiians, advocating for active engagement with local communities to form reciprocal relationships that promote learning and growth. The theoretical lens offers practical tools and applications to address the expressed needs of community members.  Effective implementation of these regenerative practices has the potential to transform Hawai’i into a destination where tourism not only benefits the economy but also enriches the environment and local communities. This transformation promises a unique travel experience, allowing tourists to gain a deeper appreciation of the natural world and contribute positively to the islands, perpetuating a cycle of reciprocity and regenerative development.

Significant advancements have been made within the field of regenerative medicine over the last few decades with the goal of creating biological substitutes to mimic tissue for research and wound healing purposes. Simply put, regenerative medicine works by understanding and then manipulating the processes by which cells communicate and proliferate for healing purposes. Before valuable progress can be made in regenerative medicine, smaller steps need to be taken first, like understanding the biomaterials that are used within regenerative medicine research. Biomaterials, which are materials that interact with cells and perform a function, are used to mimic the native extracellular matrix of cell scaffolding in regenerative medicine research. Numerous types of biomaterials exist, and it is important to choose the most appropriate material for the goal at hand. Therefore, biomaterials need to be characterized before useful research with the materials can be done. An important aspect of biomaterials that can be characterized is fluid flow through the biomaterials. This is important because adequate transport of oxygen, nutrients, waste, and soluble factors are required for cell proliferation and survival.[1] Biomaterials can be characterized based on their chemical, physical, and mechanical characteristics via many different characterization methods that are discussed in this paper. The overall goal of this research is to characterize the fluid flow metrics through Micro-porous Annealed Particle (MAP) hydrogels and others using Dynamic Contrast Enhanced – Magnetic Resonance Imaging (DCE-MRI) and computational analysis of the images via MATLAB. The analysis was utilized to analyze the fluid flow through several different biomaterial types, allowing for observational comparison between biomaterial groups. Overall, this method for characterizing fluid flow through biomaterials shows promise for future use and further understanding of biomaterials' roles in regenerative medicine. / Master of Science / Regenerative medicine encompasses the use of scientific knowledge and tools to determine novel methods for generating functioning tissues and organs. Commonly, biomaterials are used to assist in this process. Biomaterials frequently function as a solid structure that houses cells and encourages cell growth, eventually leading to tissue formation. Many different types of biomaterials exist, so it is important to determine the most suitable biomaterial for each project to improve efficiency and experiment outcomes. Biomaterial properties, like stiffness or flexibility, can be determined through various scientific testing methods. An important property of biomaterials is the fluid flow through the biomaterials. Cells housed inside biomaterials require oxygen and nutrients to grow, so it is important that fluids carrying these molecules can flow through biomaterials to provide support for the cells. This paper utilizes a computational analysis method to analyze Magnetic Resonance Imaging (MRI) images of fluid flow through biomaterials. The analysis provides information on fluid flow metrics through the biomaterials, like fluid flow velocity and direction. This analysis provides a new method for understanding biomaterial properties and provides the analysis for several different biomaterials.

Stem cells have the ability to self-renew and to differentiate into a variety of cell types. Stem cells can be found naturally in the body, can be derived from the inner cell mass of blastocysts, or can be made by dedifferentiation of adult cells. Regenerative medicine aims to utilize the potential of stem cells to treat disease and injury. The ability to create stem cell lines from a patient's own tissues allows for transplantation without immunosuppressive therapy as well as patient-specific disease modeling and drug testing. The objective of this study was to use cellular dedifferentiation to create in vitro cell lines with which to study regenerative medicine. First, we used siRNA targeted against myogenin to induce the dedifferentiation of murine C2C12 myotubes into myoblasts. Timelapse photography, immunofluorescence, and western blot analysis support successful dedifferentiation into myoblasts. However, the inability to separate the myotubes and myoblasts prior to siRNA treatment confounded the results. This system has the potential to be used to study mechanisms behind muscle cell regeneration and wound healing, but a better method for separating out the myoblasts needs to be developed before this will be achievable. Second, we used a doxycycline-inducible lentiviral vector encoding the transcription factors Oct4, Sox2, cMyc, and Klf4 to create a line of naive-like porcine induced pluripotent stem cells (iPSCs). This reprogramming vector was verified first in murine cells, the system in which it was developed. Successful production of both murine and porcine iPSC lines was achieved. Both showed alkaline phosphatase activity, immunofluorescence for pluripotency marker (Oct4, Sox2, and Nanog) expression, PCR for upregulation of endogenous pluripotency factors (Oct4, Sox2, cMyc, Klf4, and Nanog), and the ability to form embryoid bodies that expressed markers of all three germ layers. Additionally, we were able to create secondary porcine iPSC lines by exposing cellular outgrowths from embryoid bodies to doxycycline to initiate more efficient production of porcine iPSCs. The secondary porcine iPSCs were similar to the primary porcine iPSCs in their morphology, behavior, alkaline phosphatase expression, and Nanog expression with immunofluorescence. The porcine iPSCs were dependent on doxycycline to maintain pluripotency, indicating that they are not fully reprogrammed. Despite this dependence on doxycyline, this system can be used in the future to study the process of reprogramming, to develop directed differentiation protocols, and to model diseases. / Master of Science / Stem cells have the ability to self-renew and to differentiate into a variety of cell types. Stem cells can be found naturally in the body, can be derived from the inner cell mass of blastocysts (the stage of development just prior to implantation), or can be made by dedifferentiating, or reprogramming, adult cells into stem cells. Regenerative medicine aims to utilize the potential of stem cells to treat disease and injury. The ability to create stem cell lines from a patient’s own tissues allows for transplantation without immunosuppressive therapy as well as patient-specific disease modeling and drug testing. The objective of this study was to use cellular dedifferentiation to create cell lines in the laboratory with which to study regenerative medicine. First, we knocked down the expression of myogenin, a key factor in muscle cell development, to induce the dedifferentiation of mouse myotubes (adult muscle cells) into myoblasts (progenitor cells). Various methods of analysis supported successful dedifferentiation into myoblasts, but the inability to completely separate myotubes and myoblasts prior to myogenin knockdown confounded the results. With better separation of the cells, this system has the potential to be used to study mechanisms behind muscle cell regeneration and wound healing. Second, we used a viral vector encoding reprogramming factors to create both mouse and pig induced pluripotent stem cells (iPSCs) from skin cells. Pluripotent cells have the ability to differentiate into any cell type in the body, except for the placenta. Multiple pluripotency assays indicated that both the mouse and pig iPSCs were truly pluripotent. Additionally, we were able to differentiate the iPSCs into adult cells, then reprogram those back into “secondary” iPSCs. The production of secondary iPSCs is much more efficient compared to the initial creation of the primary iPSCs, which increases the usefulness of these cells for future experiments. Unfortunately, the porcine iPSCs were dependent on the reprogramming vector to maintain pluripotency. This indicates that these cells are not fully reprogrammed. Despite this, the system can still be used in the future to study the process of reprogramming, to develop cellular differentiation protocols, and to model diseases.

Osteoarthritis (OA) is a degenerative disease of diarthrodial joints causing pain and loss of joint function. Etiology is heterogeneous, but commonly involves inflammation arising from impairment of normal tissue homeostasis and/or function. A cycle of low-grade inflammation and global tissue degradation causes alteration of tissue morphology and function via primary mechanisms or inability to withstand physiological forces. Current therapies variably ameliorate symptoms but do not modify progression. Mesenchymal stem cells (MSCs) have multi-modal properties but are ineffective in ameliorating equine OA. However, anti-inflammatory activities of bone marrow derived MSCs (BMSCs) are enhanced by three-dimensional spheroid culture so equine BMSC (eBMSC) spheroids could inhibit intra-articular inflammation. The overarching hypothesis is that eBMSCs can be enhanced to produce an allogeneic eBMSC therapy that inhibits intra-articular inflammation. In vitro experiments compared differences in anti-inflammatory phenotype between spheroid and traditionally cultured monolayer eBMSCs, the viability and health of eBMSC spheroids administered through needles, and the effects of allogeneic donor on the anti-inflammatory potential of eBMSC spheroids. A model of equine LPS induced synovitis was used to investigate anti-inflammatory efficacy of spheroid eBMSCs compared to placebo or monolayer eBMSCs in vivo. eBMSCs aggregate into spheroids that have stable stem cell marker expression with increased secretion and gene expression of IL-6 and PGE2, and gene expression of SDF-1 and TSG-6. IFN𝛾 and TNFα were not produced by eBMSC spheroids and IL-10 production varied between individuals. Spheroids maintain higher viability and lower senescence than monolayer eBMSCs after injection through a needle and form in high-throughput culture without detrimental effects on expression of TSG-6, IL-6 and PGE synthases that denote an anti-inflammatory phenotype. Additionally, there is significant variation in this phenotype depending on the eBMSC donor. eBMSC spheroids reduced total nucleated cell counts and objective lameness measurements at peak levels of intra-articular inflammation compared to monolayer cultured eBMSCs in vivo. In summary, spheroids increase anti-inflammatory potential of eBMSCs and are practical for clinical use. Increased anti-inflammatory efficacy was demonstrated in a model of in vivo inflammation. This dissertation provides an understanding of the anti-inflammatory activities of eBMSC spheroids that can be used to develop an OA therapy. / Ph. D. / Osteoarthritis (OA) is a progressive disease of joints causing pain and loss of function. Multiple factors cause OA including inflammation, tissue destruction from enzymes, and breakdown due to reduced strength with continued use. This cycle of inflammation and joint tissue degradation causes joint tissue damage despite treatment with symptom relieving therapies. Mesenchymal stem cells (MSCs) are a multi-modal therapy, but have been ineffective to relieve equine OA. However, MSCs derived from bone marrow (BMSCs) have enhanced anti-inflammatory activity when produced by three-dimensional culture so BMSCs from horses could reduce joint inflammation better as three-dimensional spheroids. The overarching goal of these studies was to produce an “off the shelf” horse BMSC therapy that reduces joint inflammation both for horse treatment, and as a model for human OA. These studies compared differences between spheroid and traditionally grown (monolayer) BMSCs to reduce inflammation, survival of spheroids administered through needles, and the variability between different horse donors on the ability of spheroids to reduce inflammation. The ability of spheroids to reduce joint inflammation was determined in live horses compared to control or monolayer BMSCs. Horse BMSCs form spheroids that retain the properties that define stem cells, plus spheroid BMSCs produce factors that stem cells use to reduce the inflammatory response. Spheroids have enhanced survival compared with monolayer BMSCs after injection through a needle and spheroids can be produced in large quantities without affecting their potential to reduce inflammation. Additionally, BMSCs from different horse donors have varied potential to reduce inflammation. In live horses, donor horse BMSC spheroids reduced signs of joint inflammation and pain when inflammatory levels were highest compared to monolayer BMSCs. This dissertation demonstrates enhanced ability of spheroid BMSCs to reduce inflammation and provides key information that will be used to develop OA therapies.