Hip resurfacing arthroplasty has changed the treatment of end stage arthritis without severe deformity for young, active adults. Presently, there are varying clinical approaches to implant design selection and cementation techniques. The purpose of this project is to determine what amount of reamer-femoral component offset allows for the best cement penetration into the femoral head. Rapid prototyped femoral component models were produced with reamer femoral component offsets of 0.0 mm, 0.5 mm, and 1.0 mm. After implantation onto models of reamed femoral heads made from high-density open-cell reticulated carbon foam, cement penetration was assessed from cross-sections of the foam-implant unit. Increased offset was found to decrease the extent of cement over penetration from the dome and chamfer. Increased offset also yielded optimal cement penetration as measured from the walls. Finally, increased offset was found to increase the height of cement mantle formation while maintaining complete seating of all implants.

Off-label use of traditional Oropharyngeal Airway (OPA) as a bite-block, and the subsequential procedure of force exertion of the device by physician has caused many cases of patient’s teeth damage and monetary loss, as the patient’s incisors were damaged while clenching on the OPA during an adverse scenario called “Emergency Clenching”. To remedy this harmful situation, Bardo OPA was developed by Dr. Theodore Burdumy. The Bardo airway has unique design to transfer the clenching force from incisor to the molar. However, the Bardo OPA is one-sized, and cannot fit most of the patients like the commonly-used OPAs, such as the Berman and Gudel OPA, which have a spectrum of sizes to ensure fit. In this project, a Computer Assisted Design (CAD) simulation platform was developed to simulate the scenario where OPA is placed in a patient’s oral cavity. CAD – related technique and tools, such as 3D scanner (ScanStudio HD), RapidWorks, SolidWorks and Mimics were utilized to create the models used to construct the platform. The purpose of this platform is to generate data to support the development of additional sizes and other modification to improve the current design of the Bardo OPA. MRI sets of nine (9) patients were obtained and converted into STL mesh models. Berman and Guedel OPA were used as the standard for comparison against the Bardo OPA. It was found that the Bardo OPA was able to fit into all sample patients’ models, while these models were fitted with Berman and Guedel OPA of 70-90mm (Small to medium adult) sizes. It can only be concluded that the Bardo is compatible with these OPA sizes and there was not enough evidence to show the need for additional sizes. Nevertheless, some functional features of the Bardo OPA were found potentially harmful to the patients or ineffective. Three approaches were suggested to improve the design of the Bardo to achieve better safety and efficacy.

The goal of this research was to develop a system of individualized medicine that could be applied to dermal wounds serving as a wound dressing and synthetic extracellular matrix while delivering stem cells to the wound bed. First, fabrication parameters for electrospinning polymer fibers were determined. This involved evaluating fiber morphology with respect to polymer selection and solution concentration. Next, construct fabrication was examined to produce an integrated void space, or cargo area, suitable to maintain stem cells. In vitro studies to ensure stem cell viability and phenotype were conducted, and results supported the notion that cells could be administered to the wound site through construct pre-seeding. Lastly, in vivostudies were conducted to evaluate the construct as an applied biomaterial and as a cellular delivery device. Wound closure and quality were assessed, and neo-vascularization quantified. This project will provide insight into the tissue engineering field regarding cell-based therapies and dermal wound healing.

One countermeasure to cardiovascular spaceflight deconditioning being tested is the application of intermittent artificial gravity provided by centripetal acceleration of a human via centrifuge. However, artificial gravity protocols have not been optimized for the cardiovascular system, or any other physiological system for that matter. Before artificial gravity protocols can be optimized for the cardiovascular system, cardiovascular responses to the variables of artificial gravity need to be quantified. The research presented in this document is intended to determine how the artificial gravity variables, radius (gravity gradient) and lower limb exercise, affect cardiovascular responses during centrifugation. Net fluid (blood) shifts between body segments (thorax, abdomen, upper leg, lower leg) will be analyzed to assess the cardiovascular responses to these variables of artificial gravity, as well as to begin to understand potential mechanism(s) underlying the beneficial orthostatic tolerance response resulting from artificial gravity training. Methods: Twelve healthy males experienced the following centrifuge protocols. Protocol A: After 10 minutes of supine control, the subjects were exposed to rotational 1 Gz at radius of rotation 8.36 ft (2.54 m) for 2 minutes followed by 20 minutes alternating between 1 and 1.25 Gz. Protocol B: Same as A, but lower limb exercise (70% V02max) preceded ramps to 1.25 Gz. Protocol C: Same as A but radius of rotation 27.36 ft (8.33 m). Results: While long radius without exercise presented an increased challenge for the cardiovascular system compared to short radius without exercise, it is likely at the expense of more blood “pooling” in the abdominal region. Whereas short radius with exercise provided a significant response compared to short radius without exercise. More fluid loss occurred from the thorax and with the increased fluid loss from the thorax blood did not “pool” in the abdominal region but instead was essentially “mobilized” to the upper and lower leg. The exercise fluid shift profile presented in this document is applicable to not only artificial gravity protocol design but also proposes a mechanistic reason as to why certain artificial gravity protocols are more effective than others in increasing orthostatic tolerance.

This study combines noninvasive hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] with occlusive calibration for continuous measurement of absolute blood flow (BF), tissue blood oxygenation (StO2), and oxygen consumption rate (VO2) in exercising skeletal muscle. Subjects performed rhythmic dynamic handgrip exercise, while an optical probe connected to a hybrid NIRS/DCS flow-oximeter directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO2], [Hb], and [tHb]), StO2, relative BF (rBF), and relative VO2 (rVO2) in the forearm flexor muscles. Absolute baseline BF and VO2 were obtained through venous and arterial occlusions, respectively, and used to calibrate continuous relative parameters. Previously known problems with muscle fiber motion artifact in optical measurements were mitigated with a novel dynamometer-based gating algorithm. Nine healthy young subjects were measured and results validated against previous literature findings. Ten older subjects with fibromyalgia and thirteen age-matched healthy controls were then successfully measured to observe differences in hemodynamic and metabolic response to exercise. This study demonstrates a novel application of NIRS/DCS technology to simultaneously evaluate quantitative hemodynamic and metabolic parameters in exercising skeletal muscle. This method has broad application to research and clinical assessment of disease (e.g. peripheral vascular disease, fibromyalgia), treatment evaluation, and sports medicine.

Low back pain (LBP) is a common ailment in the United States, affecting up to 80% of adults at least once in their lifetime. Although 90% of LBP cases are considered nonspecific, recent studies show that abnormal mechanics of the lower back can be a major factor. One method of assessing the lower back mechanical environment is through perturbation experiments. An intensive literature review of perturbation systems was used to select and develop a system for the Human Musculoskeletal Biomechanics Lab (HMBL). Following construction, individuals with high/low exposure to day-long physical activity were assessed to quantify daily changes in their lower back mechanics and determine whether complete recovery occurs during overnight rest. Despite significant decrease in maximum voluntary contractions (MVC), intrinsic stiffness of the high exposure group remained constant following day-long physical activity. The final component of this Master’s project is devoted to the design of a wobble chair system for study of trunk stability. Development of the perturbation system and wobble chair are hoped to facilitate future research aimed at a better understanding of trunk mechanical and neuromuscular behaviors to prevent and treat LBP in the future.

Les dispositifs optoélectroniques organiques possèdent plusieurs avantages pour les applications dans le domaine du biomédical. Le photodétecteur organique (OPD) est un type de dispositif optoélectronique qui n’est pas encore utilisé pour la détection d’activité cérébrale. L’objectif de cette thèse a été d’explorer l’utilisation des OPD, constitués de différent matériaux donneur-accepteur d’électrons, dans le domaine des neurosciences. Nous avons présenté différent types d’OPD possédant une structure minimale, une excellente sensibilité et un grand potentiel d’intégration dans les méthodes de microfabrication existantes. Les détecteurs organiques ont été utilisés pour l’enregistrement de signaux optiques intrinsèques et de signaux fluorescents reflétant l’activité du calcium dans le cerveau. De plus, un autre aspect des OPD est présenté (en combinaison avec les transistors électrochimiques organiques (OECT)) : des systèmes électroniques biomimétiques basé sur une architecture électronique neuro-inspirée. Cette thèse démontre le potentiel des OPD pour enregistrer des activités cérébrales. Elle ouvre une nouvelle perspective, grâce à leur grande sensibilité, comme capteur optique en combinaison avec des dispositifs neuronaux implantables. Ceci élargira les frontières de l’électrophysiologie optique pour explorer les mécanismes complexes du cerveau et des maladies neurodégénératives. / Organic optoelectronic devices have many promising qualities for biomedical applications. Organic photodetectors (OPD), one type of such devices, have yet to be utilized for the detection of signals in the brain, to the best of our knowledge. The goal of this thesis was to explore the use of OPDs, based on different electron-donor and -acceptor materials in neuroscience applications. Different types of minimal-structure OPDs are presented, which have an excellent sensitivity and a high potential for incorporation into existing microfabrication methods. The organic sensors were utilized for monitoring the brain’s intrinsic optical signals and fluorescent calcium dynamics. Additionally, another aspect of these devices is presented (in combination with organic electrochemical transistors (OECT)): neuroinspired electronics, electronics that mimic biology. This thesis establishes the promise of OPDs for monitoring brain activities, which would lead to their integration, as high-sensitive micron-scale optical sensors in organic neural probes. Such device would result in exploring optical biological activities in the deep brain on the cellular level and would push the frontiers of optical-electrophysiology by giving a better understanding of complex mechanisms of the brain function and neurodegenerative diseases.

Le suivi des petits animaux utilisés dans le cadre de tests de laboratoire et l'analyse de leur comportement à distance, à faible coût et en temps réel suscitent depuis longtemps l’intérêt des chercheurs. Ceux-ci peuvent se faire par l’implantation de capteurs sans fils miniatures qui nécessitent des composants vitaux dont le plus problématique est l’antenne. En effet, la principale difficulté dans la conception d'antennes pour les dispositifs de communication bio-implantables est de fournir une structure rayonnante efficace et ce, malgré les contraintes de volume et le fort impact des tissus biologiques qui l’entourent. Si de nombreuses études ont porté sur l’utilisation d'antennes implantées dans la bande MICS (Medical Implant Communications Service) (402-405 MHz), il faut noter qu’à ces fréquences, la taille des antennes peut être un inconvénient réel dans le cas de petits animaux, d’où une recherche de miniaturisation. Une alternative consiste en l’utilisation de la technologie RFID (Radio-Frequency Identification) dans la bande UHF à 868 MHz. En effet, elle présente deux avantages primordiaux : elle facilite l'implantation du tag et ne nécessite pas l’ajout d'une batterie pour alimenter le périphérique implanté. Ce travail de thèse fait suite à un projet collaboratif financé par l’ANR (Agence Nationale de la Recherche) dans le cadre du Labex UCN@Sophia et qui a pour objectif la conception d’un système sans fils incluant aussi bien les tags RFID implantables, les antennes du lecteur et le lecteur connecté à un ordinateur se chargeant de la gestion centralisée des informations sur un serveur pour le suivi et la collecte de données de souris de laboratoire. Ce mémoire présente la conception d’antennes implantées pour tags RFID dans un modèle homogène représentant le corps d’une souris. Après l’analyse d’un bilan de liaison permettant de calculer les performances minimales de l’antenne implantée à concevoir pour une communication fiable et efficace, des antennes tags RFID passifs en 2D et en 3D ont été optimisées par différentes techniques pour atteindre des structures finales implantables ou injectables au dos d’une souris. Une caractérisation des solutions proposées en termes d’impédance, de champs E et H et de DAS (Débit d'Absorption Spécifique) a ensuite été effectuée dans un fantôme homogène. Enfin, un système d’interrogation permettant d’estimer la position de l’animal via la récupération du RSSI (Received Signal Strength Indicator) est présenté. / The monitoring of small animals in laboratory tests and the remote analysis of their behavior, with low cost and in real time interest researchers for a long time. This can be done by implanting miniature wireless sensors requiring vital components among which the most challenging is the antenna. Indeed, the main difficulty in designing antennas for bio-implantable communication devices is to provide an effective radiating structure, despite the volume constraints and the high impact of the surrounding biological tissues. Although many studies have focused on the use of implanted antennas dedicated to the MICS band (402405 MHz), it should be noted that at these frequencies, the size of the antennas can be a real disadvantage in the case of small animals, requiring miniaturization structures. Another solution consists in the using RFID (Radio-Frequency Identification) technology in the UHF band at 868 MHz. Indeed, it has two major advantages: it facilitates the implementation of the tag and does not require the addition of a battery to power the implanted device. This thesis funded by the ANR (French National Research Agency) within the framework of the Labex UCN@Sophia aims at designing a wireless system, including implantable RFID tags, reader's antennas and the reader connected to a computer that is responsible for the centralized management of information on a server for monitoring and collecting the data of laboratory mice. This thesis presents the design of implanted antennas for RFID tags in a homogeneous model representing the body of a mouse. After an analysis of a link budget allowing to determine the minimum performance of the implanted antenna to be designed for a reliable and an efficient communication, two RFID passive tag antenna designs have been optimized to obtain final structures able to be implanted or injected in the back of a mouse. A characterization of the proposed solutions in terms of impedance, E and H fields and SAR (Specific Absorption Rate) was then performed in a homogeneous phantom. Finally, an interrogation system capable to estimate the position of several animals placed in a cage thanks to the RSSI (Received Signal Strength Indicator) levels is presented.

Purpose: Due to the neurological aspects of Parkinson’s Disease (PD) and the sensitivity of eye movements to neurological issues, eye tracking has the potential to be an objective biomarker with higher accuracy in diagnosis than current clinical standards. Currently when PD is diagnosed clinically, there is an accuracy of 74% when diagnosed by a general practitioner and 82% when diagnosed by a movement disorder specialist. This study was designed to: 1. Assess eye movements as a potential biomarker for Parkinson’s Disease. 2. Determine if eye movements can distinguish between Parkinson’s Disease and commonly confounded movement disorders with parkinsonian symptoms. 3. Determine if the eye movements of Rapid Eye Movement Behavior Disorder (RBD) patients who will likely convert to PD are distinguishable from healthy controls and if RBD patients have eye movements with similar features to PD. Methods: The eye movements of 160 subjects (43 healthy controls, 63 PD, 31 REM Behavior Disorder, and 22 Other Parkinsonisms) were recorded at 500 Hz and analyzed. Each subject performed five eye tracking tasks that included reflexive saccades, inhibition of reflexive saccades, predictive saccades, and reading. Based on an analysis of selected eye movement measurement parameters, a multivariable logistic regression model was developed that compared: PD vs. Control, PD vs. “Other”, PD vs RBD, and Control vs RBD. The resulting predictive model was then assessed for accuracy, sensitivity, and specificity. Results: After screening, the most statistically significant predictors that were included in the final multivariate model were: Site, Sex, Age, Age squared, UPDRS Score, mean absolute fixation velocity (Horizontal Step Task), saccadic duration, average saccadic velocity, and mean fixation velocity (Predictive Task). The model predicted with an accuracy of: 92% for Controls, 88% for PD, 86% for RBD, and 68% for Other Parkinsonisms. The model was best at distinguishing between PD and Other Parkinsomisms with an accuracy of 89% and RBD and Controls with an accuracy of 88%. Conclusion: This research found that specific combinations of eye tracking parameters from simple tasks can be used to distinguish between PD and commonly confounded movement disorders with parkinsonism symptoms. The model’s ability to distinguish between groups indicates that in a confirmatory study we should have relatively high accuracy in discriminating between groups. This model is able to accurately distinguish Controls from RBDs, however due to an insufficient number of follow-up visits to date, the current study is unable to confirm if the RBDs tested will convert to PD. With such high error rates in diagnosing PD clinically, this model is a potentially beneficial and could serve as an easy screening tool to add to the suite of diagnostic tests and improve clinician’s ability to diagnose accurately.

The development of treatments for neurological disorders such as Alzheimer’s and Parkinson’s disease begins by understanding what these diseases affect and the consequences of further manifestation. One particular region where these diseases can produce substantial problems is the blood-brain barrier (BBB). The BBB is the selective diffusion barrier between the circulating blood and the brain. The barrier’s main function is to maintain CNS homeostasis and protect the brain from the extracellular environment. The progression of BBB research has advanced to the point where many have modeled the BBB in vitro with aims of further characterizing and testing the barrier. Particularly, the pharmaceutical industry has gained interest in this field of research to improve drug development and obtain novel treatments for patients so the need for an improved model of the BBB is pertinent in their discovery. In the Cal Poly Tissue Engineering lab, an in vitro tissue engineered BBB system has previously been obtained and characterized for the initial investigation of the barrier and its components. However, certain limitations existed with use of the commercial system. Therefore, the focus of this thesis was to improve upon the capabilities and limitations of this commercialized system to allow further expansion of BBB research. The work performed was based on three aims: first to design and develop an in-house bioreactor system that could be used to cultivate the BBB; second, to characterize flow and functional capabilities of the bioreactor; third, to develop protocols for the overall use of the bioreactor, to ultimately allow co-cultures of BAEC and C6 glioma cells, and further the progression toward creating an in vitro model of the BBB. The work of this thesis demonstrates development of an in-house custom bioreactor system that can successfully culture cells. Results showed that the system was reusable, could be sterilized and monitored, was easily used by students trained in the laboratory, and allowed non-destructive scaffold extraction. This thesis also discusses the next set of experiments that will lead to an in vitro model of the BBB.