CNPq / Este trabalho apresenta o estudo de um método para a determinação da posição e orientação de uma bobina implantável em relação à bobina transmissora localizada externamente ao paciente. No aspecto elétrico, conhecer a posição e orientação da bobina implantada permite um maior domínio sobre o posicionamento do enlace e, consequentemente, das características de eficiência e potência entregue ao secundário, i.e. ao IMD. Já no aspecto clínico, detectar e determinar a posição da bobina implantável e, se possível, do IMD, pode auxiliar na determinação de possíveis movimentações do dispositivo na região implantada que podem influenciar o seu desempenho. Neste sentido, realizou-se análises teóricas a cerca da indutância mútua, do coeficiente de acoplamento magnético e de sistemas de transferência de energia sem fio (WPT) a duas bobinas. Por meio do modelo matemático implementado no software Matlab e o projeto experimental de sistemas de WPT a duas bobinas, avaliou-se a influência de desalinhamentos laterais e angulares sobre o acoplamento magnético. A partir das características observadas, descreveu-se os procedimentos necessários para estimar a posição e orientação relativa da bobina do dispositivo implantável apenas mensurando os parâmetros elétricos do primário. Em uma avaliação preliminar, por meio de testes virtuais, observou-se um erro médio e incerteza padrão na determinação da posição relativa de 2,4 mm e 1,1 mm, respectivamente, que se comparada às dimensões das bobinas (40 mm de diâmetro para bobina externa e 5,5 mm para a bobina implantável) indicam uma exatidão adequada. Para a determinação do ângulo relativo o método também apresentou resultados promissores, uma vez que o erro médio foi de 7º e a incerteza padrão obtida de 8,2º. Desta forma, o método estudado possibilita o desenvolvimento de equipamentos para determinação da posição e orientação relativa de uma bobina implantável mensurando apenas a corrente no primário, sem a necessidade de circuitos adicionais no IMD ou a utilização de equipamentos de imagem médicos. / This paper presents the study of a method for determining the implanted coil position and orientation relative to the transmitter coil externally located to the patient. In the electrical aspect, knowing the implanted coil position and orientation allows greater control over the placement of the link and thus the efficiency of features and power delivered to the secondary, i.e. the IMD. In the clinical aspect, detect and determine the implantable coil position, if possible, the IMD can assist in determining possible device movements in the implanted area that can influence their performance. In this sense, a theoretical analysis about the mutual inductance, the magnetic coupling coefficient and two coils wireless power transfer (WPT) systems was realized. Through mathematical model implemented in Matlab and experimental design of two coil WPT systems, the influence of lateral and angular misalignment on the magnetic coupling was assessed. From the observed characteristics, was described the necessary procedures to estimate the relative position and orientation of the implantable device coil only measuring the primary electrical parameters. In a preliminary evaluation, through virtual testing, there was an average error and standard deviation in determining the relative position of 2.4 mm and 1.1 mm, respectively, compared to the dimensions of the coils (40 mm diameter to external coil and 5.5 mm for implantable coil) indicate adequate accuracy. To the relative angle the method also yielded promising results, since the average error was 7° and the standard deviation obtained 8.2°. Thus, the method studied enables the development of equipment for determining the implanted coil relative position and orientation measuring only the primary current without the need for additional circuitry in IMD or the use of medical imaging equipment.

Indiana University-Purdue University Indianapolis (IUPUI) / Type I diabetes is an autoimmune disorder characterized by the loss of insulin producing islet cell mass. While daily insulin injection provides an easy means of glycemic control, it does not prevent long-term complications associated with diabetes. Islet transplantation has been suggested as a permanent cure for type 1 diabetes. However, the recurrence of host immunity and shortage of donor islets hinder the prevalence of islet transplantation. Biomaterial strategies provide an alternative route to solving the problems associated with host immune response and shortage of donor islets. One highly recognized platform for achieving these goals are hydrogels, which are hydrophilic crosslinked polymers with tissue-like elasticity and high permeability. Hydrogels prepared from poly(ethylene glycol) (PEG) derivatives are increasingly used for a variety of tissue engineering applications, including encapsulation of pancreatic islets and serving as a material platform for pseudo-islet differentiation. PEG hydrogels formed by mild and rapid thiol-ene photo-click reactions are particularly useful for studying cell behaviors in three-dimension (3D). Thiol-ene PEG-based hydrogels can be rendered biodegradable if appropriate macromer and cross-linker chemistry is employed. However, the influence of hydrogel matrix properties on the survival, growth, and morphogenesis of cells in 3D has not been fully evaluated. This thesis aims at using norbornene-functionalized PEG macromers to prepare thiol-ene hydrogels with various stiffness and degradability, from which to study the influence of hydrogel properties on pancreatic cell fate processes in 3D. Toward establishing an adaptable hydrogel platform for pancreatic tissue engineering, this thesis systematically studies the influence of hydrogel properties on encapsulated endocrine cells (e.g., MIN6 beta-cells) and exocrine cells (PANC-1 cells), as well as human mesenchymal stem cells (hMSC). It was found that thiol-ene photo-click hydrogels provide a cytocompatible environment for 3D culture of these cells. However, cell viability was negatively affected in hydrogels with higher cross-linking density. In contrast to a monolayer when cultured on a 2D surface, cells with epithelial characteristic formed clusters and cells with mesenchymal features retained single cell morphology in 3D. Although cells survived in all hydrogel formulations studied, the degree of proliferation, and the size and morphology of cell clusters formed in 3D were significantly influenced by hydrogel matrix compositions. For example: encapsulating cells in hydrogels formed by hydrolytically degradable macromer positively influenced cell survival indicated by increased proliferation. In addition, when cells were encapsulated in thiol-ene gels lacking cell-adhesive motifs, hydrolytic gel degradation promoted their survival and proliferation. Further, adjusting peptide crosslinker type and immobilized ECM-mimetic bioactive cues provide control over cell fate by determining whether observed cellular morphogenesis is cell-mediated or matrix-controlled. These fundamental studies have established PEG-peptide hydrogels formed by thiol-ene photo-click reaction as a suitable platform for pancreatic tissue engineering

Indiana University-Purdue University Indianapolis (IUPUI) / In recent years, magnesium alloys, due to their high strength and biocompatibility, have attracted significant interest in medical applications, such as cardiovascular stents, orthopedic implants, and devices. To overcome the high corrosion rate of magnesium alloys, coatings have been developed on the alloy surface. Most coating methods, such as anodic oxidation, polymer coating and chemical conversion coating, cannot produce satisfactory coating to be used in human body environment. Recent studies demonstrate that micro-arc oxidation (MAO) technique can produce hard, dense, wear-resistant and well-adherent oxide coatings for light metals such as aluminum, magnesium, and titanium. Though there are many previous studies, the understanding of processing conditions on coating performance remains elusive. Moreover, previous tests were done in simulated body fluid. No test has been done in a cell culture medium, which is much closer to human body environment than simulated body fluid. In this study, the effect of MAO processing time (1 minute, 5 minutes, 15 minutes, and 20 minutes) on the electrochemical behaviors of the coating in both conventional simulated body fluid and a cell culture medium has been investigated. Additionally a new electrolyte (12 g/L Na2SiO3, 4 g/L NaF and 4 ml/L C3H8O3) has been used in the MAO coating process. Electrochemical behaviors were measured by performing potentiodynamic polarization and electrochemical impedance spectroscopy tests. In addition to the tests in simulated body fluid, the MAO-coated and uncoated samples were immersed in a cell culture medium to investigate the corrosion behaviors and compare the difference in these two kinds of media. The results show that in the immersion tests in conventional simulated body fluid, the 20-minute MAO coated sample has the best resistance to corrosion due to the largest coating thickness. In contrast, in the cell culture medium, all MAO coated samples demonstrate a similar high corrosion resistance behavior, independent of MAO processing time. This is probably due to the organic passive layers formed on the coating surfaces. Additionally, a preliminary finite element model has been developed to simulate the immersion test of magnesium alloy in simulated body fluid. Comparison between the predicted corrosion current density and experimental data is discussed.

Indiana University-Purdue University Indianapolis (IUPUI) / Dicalcium phosphate dihydrate (DCPD) cements have been used for bone repair due to its excellent biocompatibility and resorbability. However, DCPD cements are typically weak and brittle. To overcome these limitations, the sodium citrate used as a setting regulator and the coating of poly-L-lactide acid (PLLA) technique have been proposed in this study. The first purpose of this thesis is to develop composite PLLA/DCPD scaffolds with enhanced toughness by PLLA coating. The second purpose is to examine the biocompatibility of the scaffolds. The final purpose is to investigate the degradation behaviors of DCPD and PLLA/DCPD scaffolds. In this experiment, DCPD cements were synthesized from monocalcium phosphate monohydrate (MCPM) and 𝛽-tricalcium phosphate (𝛽 –TCP) by using deionized water and sodium citrate as liquid components. The samples were prepared with powder to liquid ratio (P/L) at 1.00, 1.25 and 1.50. To fabricate the PLLA/DCPD composite samples, DCPD samples were coated with 5 % PLLA. The samples were characterized mechanical properties, such as porosity, diametral tensile strength, and fracture energy. The mechanical properties of DCPD scaffolds with and without PLLA coating after the in vitro static degradation (day 1, week1, 4, and 6) and in vitro dynamic degradation (day 1, week 1, 2, 4, 6, and 8) were investigated by measuring their weight loss, fracture energy, and pH of phosphate buffer solution. In addition, the dog bone marrow stromal stem cells (dBMSCs) adhesion on DCPD and PLLA/DCPD composite samples were examined by scanning electron microscopy. The cell proliferation and differentiation in the medium conditioned with DCPD and PLLA/DCPD composite samples were studied by XTT (2,3-Bis(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide inner salt), and alkaline phosphatase (ALP) assay, respectively. The addition of sodium citrate and PLLA coating played a crucial role in improving the mechanical properties of the samples by increasing the diametral tensile strength from 0.50 ± 0.15 MPa to 2.70 ± 0.54 MPa and increasing the fracture energy from 0.76 ± 0.18 N-mm to 12.67 ± 4.97 N-mm. The DCPD and PLLA/DCPD composite samples were compatible with dBMSCs and the cells were able to proliferate and differentiate in the conditioned medium. The degradation rate of DCPD and PLLA/DCPD samples were not significant different (p > 0.05). However, the DCPD and PLLA/DCPD composite samples those used sodium citrate as a liquid component was found to degrade faster than the groups that use deionized water as liquid component

Indiana University-Purdue University Indianapolis (IUPUI) / The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.