The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 µm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected pores facilitates cell infiltration and tissue remodelling in vitro, suggesting its high potential in regenerative medicine and tissue engineering applications. In the second part of the dissertation, the versatility of breath figure polymers was explored as a reverse template to create micropatterned soft materials. Unlike traditional lithographic masters, the breath figure assembly is a simple and cost-effective approach to create micro/nano sized “bead†like uniform patterns on the surface of hydrogels and biopolymers. By incorporating iron nanoparticles into the pores, this technique was extended to form hydrogels decorated with nanoparticles specifically in the pattern. The morphology features and the functional characteristics were demonstrated through scanning electron microscopy. The potential applications of these micro-fabricated materials in biosensors and cell culture substrates are outlined. / acase@tulane.edu

Nosocomial infections associated with implanted medical- devices are on the rise due to a growing immunocompromised patient population. The organisms of interest in this study are Pseudomonas aeruginosa and Candida albicans. These organisms are opportunistic pathogens and are frequently implicated as the cause of infection and colonization of medical devices. P. aeruginosa is a motile gram-negative bacterium that is able to suppress the growth of C. albicans. Quourm sensing mimicry and biofilm formation on the hyphal surface of C. albicans by P. aeruginosa aids in suppression. C. albicans is a dimorphic fungus capable of quorum sensing with E,E-farnesol and is a central focus in this work. The goal of this project is to determine changes in protein expression when P. aeruginosa is exposed to E,E,-farnesol using 2D DIGE®. Changes in the cytosolic proteome of P. aeruginosa expose metabolic shifts that result in suppression of C. albicans. This work summarizes the effect of growth phase and concentration of E,E-farnesol on P. aeruginosa PAO1 and GSU3. Preliminary results reveal a general response of P. aeruginosa to C. albicans as changes in relevant metabolic nodes that affect pyocyanin production and the induction of virulence factors that lead to the killing of C. albicans. The overall goal of this study was to generate a profile of protein expression where a variety of conditions to further characterize the response could be easily assayed.

Background: Health economic evaluations are becoming an increasingly important means of analysing which care alternative resource utilisation is the most cost effective. It is a new topic in the medical device industry that causes much uncertainty and unstructured use of the actors involved. Study questions: Why is it difficult to develop, implement and disseminate this standardized health economic evaluation models in medical technology? Is there a possibility to standardize health economic evaluations within the medical device industry? Purpose: The purpose of this study is to investigate the standardization issues for health economic evaluations within the medical device industry. Method: A qualitative approach was used in the form of interviews with five actors that are active or have a connection to the medical device industry. The data collection consists of journals, reports, Internet searches and literature among other things. Conclusion: It is possible to standardize, but with certain restrictions such as the county council's budget, influence of industry-specific factors, lack of knowledge and the important interaction between actors.

Currently, biopharmaceuticals including vaccines, proteins, and DNA are delivered almost exclusively through the parenteral route using hypodermic needles. However, injection by hypodermic needles generates pain and causes bleeding. Disposal of these needles also produces biohazardous sharp waste. An alternative delivery tool called microneedles may solve these issues. Microneedles are micron-size needles that deliver drugs or biopharmaceuticals into skin by creating tiny channels in the skin. This thesis focuses on dissolving microneedles in which the needle tips dissolve and release the encapsulated drug or vaccine upon insertion. The project aimed to (i) design and optimize dissolving microneedles for efficient drug and vaccine delivery to the skin, (ii) maintain vaccine stability over long-term storage, and (iii) immunize animals using vaccine encapsulated microneedles. The results showed that influenza vaccine encapsulated in microneedles was more thermally stable than unprocessed vaccine solution over prolonged periods of storage time. In addition, mice immunized with microneedles containing influenza vaccine offered full protection against lethal influenza virus infection. As a result, we envision the newly developed dissolving microneedle system can be a safe, patient compliant, easy to-use and self-administered method for rapid drug and vaccine delivery to the skin.

Novel techniques for high-performance wireless power transmission and data interfacing with implantable medical devices (IMDs) were proposed. Several system- and circuit-level techniques were developed towards the design of a novel wireless data and power transmission link for a multi-channel inductively-powered wireless implantable neural-recording and stimulation system. Such wireless data and power transmission techniques have promising prospects for use in IMDs such as biosensors and neural recording/stimulation devices, neural interfacing experiments in enriched environments, radio-frequency identification (RFID), smartcards, near-field communication (NFC), wireless sensors, and charging mobile devices and electric vehicles. The contributions in wireless power transfer are the development of an RFID-based closed-loop power transmission system, a high-performance 3-coil link with optimal design procedure, circuit-based theoretical foundation for magnetic-resonance-based power transmission using multiple coils, a figure-of-merit for designing high-performance inductive links, a low-power and adaptive power management and data transceiver ASIC to be used as a general-purpose power module for wireless electrophysiology experiments, and a Q-modulated inductive link for automatic load matching. In wireless data transfer, the contributions are the development of a new modulation technique called pulse-delay modulation for low-power and wideband near-field data communication and a pulse-width-modulation impulse-radio ultra-wideband transceiver for low-power and wideband far-field data transmission.

Unlike hardware, software does not degrade over time or frequency use. This is good for software. Also unlike hardware, software can be easily changed. This unique characteristic gives software much of its power, but is also responsible for possible failures in software applications. When software is used within medical devices, software failures may result in bodily injury or death. As a result, regulations have been imposed on the makers of medical devices to ensure their safety, which includes the safety of the devices’ software. The U.S. Food and Drug Administration requires establishment of systems and control processes to ensure quality devices. A principal part of the quality assurance effort is testing. This paper explores the unique role of software testing in the design, development, and release of software used for medical devices and applications. It also provides practical, industry-driven guidance on medical device software testing techniques and strategies. / text

Magistro baigiamajame darbe yra nagrinėjamas dabartinis nanomedicinos teisinis reglamentavimas ES ir JAV. Ši tema Lietuvoje iki šiol dar nebuvo tyrinėjimų objektu. Pirmoji darbo dalis supažindina skaitytoją su nanomedicina bei su ja susijusių sąvokų problematiką. Antroji dalis atskleidžia nanomedicinos teisinio reglamentavimo prielaidas ES, o trečioji dalis – JAV. Be to, atsižvelgiant į gautus rezultatus, yra įvertinamos galimos nanomedicinos teisinio reglamentavimo perspektyvos ateityje. Darbe plačiai analizuojami atitinkami pasirinktų tarptautinės teisės subjektų teisės aktai bei specialioji teisinė literatūra (įvairių institucijų dokumentai, teisės mokslininkų darbai) bei tam tikra mokslinė-techninė literatūra (įvairių institucijų ir organizacijų ataskaitos ir tyrimai, mokslininkų tyrimai). / The master thesis researches the current regulation of nanomedicine in the EU and the US. Until now, this topic has not yet been researched in Lithuania. In the first part of the thesis nanomedicine and the problem of nanomedicine-related definitions are introduced to the reader. The second part reveals the basis of the regulation of nanomedicine in the EU, and the third part – in the US. Furthermore, considering the achieved results, the perspective of the future regulation of nanomedicine is assessed. The thesis extensively analyses the legal acts of the chosen subjects of international law and specific legal literature (documents of various institutions, works of law scholars) as well as some scientific-technical literature (reports and researches of various institutions and organizations, scientists’ researches).

All artificial organ systems and medical devices that operate in direct contact with blood elicit activation of coagulation and platelets, and their long-term use often necessitates antithrombotic therapies that carry significant cost and bleeding risk. Thrombomodulin (TM) is a major endogenous inhibitor of blood coagulation localized on the endothelial cell surface. The overall objective of this research is to develop clinically durable synthetic materials by incorporating TM as a solid-supported film to actively and sustainably attenuate thrombus formation at the blood-contacting interface. During the course of this research, we developed site-specific approaches to covalently attach TM on the luminal surface of commercial vascular grafts using bioorthogonal chemistry that was compatible with ethylene oxide sterilization. Notably, we demonstrated the superior efficacy of TM to reduce platelet deposition compared with commercial heparin modified grafts using a non-human primate model of acute graft thrombosis. Finally, we optimized a novel reversible chemistry to rapidly and repeatedly regenerate immobilized TM, with the potential to significantly extend the lifetime of biologically active films.

For decades, reliability engineering techniques have been successfully applied in many industries to improve the performance of equipment maintenance management. Numerous inspection and optimization models are developed and widely used to achieve maintenance excellence, i.e. the balance of performance, risk, resources and cost to reach to an optimal solution. However, the application of all these techniques and models to medical devices is new. Hospitals, due to possessing a large number of difference devices, can benefit significantly if the optimization techniques are used properly in the equipment management processes. Most research in the area of reliability engineering for medical equipment mainly considers the devices in their design or manufacturing stage and suggests some techniques to improve the reliability. To this point, best maintenance strategies for medical equipment in their operating context have not been considered. We aim to address this gap and propose methods to improve current maintenance strategies in the healthcare industry. More specifically, we first identify or propose the criteria which are important to assess the criticality of medical devices, and propose a model for the prioritization of medical equipment for maintenance decisions. The model is a novel application of multi-criteria decision making methodology to prioritize medical devices in a hospital according to their criticality. The devices with high level of criticality should be included in the hospital’s maintenance management program. Then, we propose a method to statistically analyze maintenance data for complex medical devices with censoring and missing information. We present a classification of failure types and establish policies for analyzing data at different levels of the device. Moreover, a new method for trend analysis of censored failure data is proposed. A novel feature of this work is that it considers dependent failure histories which are censored by inspection intervals. Trend analysis of this type of data has not been discussed in the literature. Finally, we introduce some assumptions based on the results of the analysis, and develop several new models to find the optimal inspection interval for a system subject to hard and soft failures. Hard failures are instantaneously revealed and fixed. Soft failures are only rectified at inspections. They do not halt the system, although they reduce its performance or productivity. The models are constructed for two main cases with the assumption of periodic inspections, and periodic and opportunistic inspections, respectively. All numerical examples and case studies presented in the dissertation are adapted from the maintenance data received from a Canadian hospital.

For decades, reliability engineering techniques have been successfully applied in many industries to improve the performance of equipment maintenance management. Numerous inspection and optimization models are developed and widely used to achieve maintenance excellence, i.e. the balance of performance, risk, resources and cost to reach to an optimal solution. However, the application of all these techniques and models to medical devices is new. Hospitals, due to possessing a large number of difference devices, can benefit significantly if the optimization techniques are used properly in the equipment management processes. Most research in the area of reliability engineering for medical equipment mainly considers the devices in their design or manufacturing stage and suggests some techniques to improve the reliability. To this point, best maintenance strategies for medical equipment in their operating context have not been considered. We aim to address this gap and propose methods to improve current maintenance strategies in the healthcare industry. More specifically, we first identify or propose the criteria which are important to assess the criticality of medical devices, and propose a model for the prioritization of medical equipment for maintenance decisions. The model is a novel application of multi-criteria decision making methodology to prioritize medical devices in a hospital according to their criticality. The devices with high level of criticality should be included in the hospital’s maintenance management program. Then, we propose a method to statistically analyze maintenance data for complex medical devices with censoring and missing information. We present a classification of failure types and establish policies for analyzing data at different levels of the device. Moreover, a new method for trend analysis of censored failure data is proposed. A novel feature of this work is that it considers dependent failure histories which are censored by inspection intervals. Trend analysis of this type of data has not been discussed in the literature. Finally, we introduce some assumptions based on the results of the analysis, and develop several new models to find the optimal inspection interval for a system subject to hard and soft failures. Hard failures are instantaneously revealed and fixed. Soft failures are only rectified at inspections. They do not halt the system, although they reduce its performance or productivity. The models are constructed for two main cases with the assumption of periodic inspections, and periodic and opportunistic inspections, respectively. All numerical examples and case studies presented in the dissertation are adapted from the maintenance data received from a Canadian hospital.