Three-dimensional (3D) printing techniques for patient-individual medicine has found its way into veterinary neurosurgery. Because of the high accuracy of 3D printed specific neurosurgical navigation devices, it seems to be a safe and reliable option to use patient- individual constructions for sampling brain tissue. Due to the complexity and vulnerability of the brain a particularly precise and safe procedure is required. In a recent cadaver study a better accuracy for the 3D printed MRI-based patient individual stereotactic brain biopsy device for dogs is determined compared to the accuracies of other biopsy systems which are currently used in veterinary medicine. This case report describes the clinical use of this 3D printed MRI-based patient individual brain biopsy device for brain sampling in three dogs. The system was characterized by a simple handling. Furthermore, it was an effective and reliable tool to gain diagnostic brain biopsy samples in dogs with no significant side effects.

Preterm birth is a global health challenge and the leading cause of neonatal mortality. Each year, about 15 million babies are born preterm globally. Traditional tools that have been exploited for the detection of preterm birth biomarkers are expensive, time consuming, or lack multiplexing capabilities. The work described in this dissertation highlights techniques developed to detect preterm birth biomarkers rapidly and accurately in the effort to mitigate preterm birth risk. In this dissertation, I first demonstrated the use of stereolithography digital light processing-based 3D printing and microfluidics for the development of microfluidic devices that had microvalves for fluid control. I then used these devices for microchip electrophoresis and fluorescence detection of five preterm birth biomarkers from a published panel. Next, I presented developments in 3D printed microchip electrophoresis device design. I separated amino acids and preterm birth biomarkers in a serpentine device design, obtaining good resolution, separation efficiency, and improved preterm birth biomarker peak capacity. Finally, I demonstrated the integration of solid-phase extraction with microchip electrophoresis in 3D printed microfluidic devices. These integrated devices enabled a seamless transition from preterm birth biomarker enrichment and labeling to microchip electrophoresis separation and fluorescence detection. The work described in this dissertation shows promise in advancing key tools needed to address preterm birth risk rapidly and effectively.

I och med att additiv tillverkning blir allt vanligare i dagens samhälle kommer dess ekologiska, samt ekonomiska effekter bli alltmer tydliga och viktiga att ta i beaktning. Tekniken utvecklas och är numera tillgänglig för i stort sett alla. Detta har gjort att 3D-skrivare bland privatpersoner blivit vanligt förekommande. Det har lett till att mer filament går åt till användning av 3D-skrivare, vilket också leder till att mer material går till spillo. Ett av de vanligaste filamentmaterialen inom detta område är PLA. PLA har många fördelar när det kommer till 3D-skrivning, en av nackdelarna är dock svårigheten med att ta till vara på spillmaterialet då det är svårt att återvinna. Detta bidrar till ett ökat behov av att kunna återvinna filamentet själv, och vad kan då vara bättre än att göra det till nytt filament som kan användas igen? Detta är bra ur både ekonomiska och ekologiska hållbarhetsaspekter. Av denna anledning har en extruderingsmaskin designats så att privatpersoner och mindre aktörer ska kunna bygga en egen. På så sätt kan de ta hand om sitt spillmaterial på ett vis som närmar sig en cirkulär ekonomi. Projektet inleddes med en bakgrundsundersökning för att undersöka befintliga lösningsalternativ som redan finns och för att få tips och inspiration. Sedan genomfördes en idégenereringsprocess för att ta fram så många idéer som möjligt för att därigenom förbättra möjligheterna till att hitta en exceptionell lösning. När ett koncept hade valts gjordes jämförelser mellan olika komponenter. Sedan gjordes beräkningar på de valda komponenterna. Detta för att kunna dimensionera dem, delvis för att vara säker på att den håller, men även för att veta hur mycket värme och mekanisk energi som kommer att behöva tillföras i maskinen för att den ska fungera som tänkt. Ett komplett designförslag har tagits fram tillsammans med dimensioner på komponenter för att underlätta för ett eventuellt privat byggprojekt av denna extruderingsmaskin. Vissa ändringar kan göras beroende på budget och tillgänglighet av komponenter. De ändringar som görs kan leda till att även beräkningar behöver göras om eller justeras. Flera av måtten och dimensionerna på vissa komponenter kan ses som överdrivna, detta är på grund av att de ska klara det högsta tryck och krafter som kan uppstå. Dessa uppstår enbart när det satt stopp i matrisen. Att det sätter stopp helt och hållet kommer troligtvis vara ovanligt, men om det händer är det viktigt att maskinen klarar av ett sådant stopp. Till sist kommer alla inställningar behöva justeras och testas på egen hand. Detta är på grund av att maskinen inte har byggts, utan enbart är ett koncept. Dessutom kommer den troligtvis fungera lite annorlunda för alla som bygger den då det kommer att vara skillnader i montering och komponenter. / In today's society additive manufacturing is getting more and more common. The technique is developing and is within reach for almost everyone. It is within the private sector the biggest growth of popularity can be seen. The increased usage of this technology has led to increased usage of plastic within this field. This means that the waste has increased as well. One of the most common materials for 3D-printing is PLA, this is because of a few different benefits. Although it has its cons, one of the bigger drawbacks is that it is hard to recycle. There are very few recycling facilities that can take care of PLA. This means that it is necessary to find another way to handle the otherwise wasted PLA. One way to do this is by making it possible for people to do it themselves, therefore the goal of this project, to develop an extruder for individuals. The extruder is supposed to use old PLA-prints to make new filament. This is good from an ecological perspective as well as an economic one. The extruder is designed to make it possible for the user to assemble it on their own. The project started with a background search, this was to get a better picture of the problem, but also to see what alternative solutions already exists. After this the phase of brainstorming as many ideas as possible started. When a concept had been chosen it was developed even further and calculations were done to ensure that it would work as intended. The calculations contained aspects such as strength of the base and pipe, but also the amount of energy needed from the motor and heaters to fulfill their respective functions. A complete design proposal for the extruder has been established, this together with supporting calculations and measurements for the different components. A few changes can be done to modify the machine for individual needs, however the calculations might have to be adapted depending on the changes that are made. A few of the dimensions on certain components might seem exaggerated. This is because they need to be able to handle the highest pressures and forces that may occur. These pressures and forces are only reached when the machine gets clogged up. The machine clogging should be unusual, but once it happens it might break without proper dimensions. At last smaller adjustments might have to be made by the user. This is because the machine has not been built, it is just a concept. Also, there will be differences depending on what specific component is chosen and the individual assembling process.

In this study, the mechanical properties of a fiber-reinforced cementitious composite (FRCC) were derived for specimens fabricated using two different methods of casting: conventional cast construction and pump-driven extrusion. Through the extrusion process, fibers are more likely to be oriented along the length of the member being cast and will therefore be more efficient since they are aligned parallel to the tensile stresses produced in flexure testing. The FRCC employed 0.5% and 1% polyvinyl alcohol (PVA) fiber reinforcement by volume. The flexural properties of FRCC were determined using four-point bend tests according to a modified ASTM C1609. Calculations included the modulus of rupture (MOR) and flexural toughness based on load-deflection curves. The fracture properties of FRCC were determined by using three-point bend tests on the same design but having notched beams using the two-parameter fracture model (TPFM). Calculations included the Mode I critical stress intensity factor (KIC), the critical crack tip opening displacement (CTODc), the strain energy release rate (GIC), and the total fracture energy (GF). The results show that enhanced ductility and post-peak behavior are achieved in concrete to which fibers have been added, as has been demonstrated in other studies, although this study further demonstrated how preferential fiber alignment produced via an extrusion can enhance fracture and flexural properties of cementitious composites. / Master of Science / Fiber-reinforced cementitious composite (FRCC) is a type of cementitious composite that contains fibers that are added to the mixture to improve its strength, durability, and ductility. One of the key factors of FRCC that affects its mechanical properties is the fiber alignment. Extrusion can be used as a method to preferentially align the fibers in order to maximize the benefit of fibers. Extruded FRCC can be pumped through a nozzle, making fiber alignment a convenient option for construction projects where traditional concrete placement methods would be difficult. One of the main benefits of aligning fibers in pump-extruded FRCC is that it can improve cementitious composites' fracture and flexural toughness. Fracture toughness refers to the ability of a material to resist crack propagation, while flexural toughness refers to its ability to withstand bending. By adding fibers to the mixture, the fibers act as reinforcement and help to distribute stress more evenly throughout the material, leading to increased strength and ductility. Furthermore, the alignment of fibers within the mixture also plays a critical role in the fracture and flexural strength of the material. Research has shown that when fibers are aligned in a specific direction, they can improve the tensile strength of the concrete and decrease the likelihood of crack propagation. This can be especially useful in structures that are exposed to seismic activity or long-lasting heavy loads. Overall, the use of pump extrusion-based method as a fiber alignment for FRCC can significantly improve the fracture and flexural strength of concrete. This makes it an attractive option for construction projects that require strong and durable members.

Le cancer du col de l’utérus, le quatrième cancer le plus répandu chez la femme, affecte principalement les régions à faible et moyen revenu. Alors que les taux d’incidence et de mortalité sont les plus élevés dans les pays en développement, l’accessibilité aux systèmes de dépistage et traitement y est limitée. La curiethérapie (BT) à haut débit de dose (HDR) fait partie du traitement standard recommandé pour les cancers du col de l’utérus en stade localement avancé IIIB-IVA. Les applicateurs commerciaux pour les traitements de BT combinés intracavitaire et interstitiel (IC/IS) sont très chers et n’offrent que des positions et orientations fixes pour les aiguilles IS. L’applicateur à demi anneaux Montréal (MSR) propose la modification d’un applicateur IC commercial par l’ajout de capuchons Adaptiiv, imprimés 3D à faible coût avec la technologie de photopolymérisation (SLA) en résine stérilisable et biocompatible, permettant l’intégration et l’optimisation d’un maximum de 10 trajectoires IS. Dans cette étude, une nouvelle génération de capuchons réduit le diamètre de l’applicateur MSR d’au plus 8.4 mm et introduit quatre positions d’aiguilles IS additionnelles à l’intérieur du demi anneau (SR), deux positions par SR. Ces capuchons sont imprimés avec la résine BioMed Clear sur l’imprimante SLA Form3B (Formlabs Inc., Massachusetts, États-Unis) et accommodent des angles d’aiguilles IS allant jusqu’à 45°. Les erreurs sur les trajectoires des aiguilles IS de l’applicateur MSR avec les nouveaux capuchons sont évaluées dans un fantôme gynécologique (GYN), développé dans le cadre de ce projet, et comparées dans une analyse statistique aux performances de l’applicateur Venezia (Elekta, Stockholm, Suède). Le fantôme GYN développé comprend une masse implantable en silicone, dont la texture est optimisée avec l’expérience clinique de deux radio-oncologistes spécialisées en BT GYN pour simuler l’insertion d’implants cliniques, pouvant supporter un grand nombre d’aiguilles IS. L’étude sur ce fantôme a démontré que la performance de l’un des capuchons de la nouvelle génération ne présente pas de différence statistiquement et cliniquement significative avec l’applicateur Venezia. Les performances de ce capuchon sont reproductibles dans les différents milieux en silicone et en utilisant différents types d’aiguilles IS. / Cervical cancer, the fourth most common cancer in women, mainly affects low- and middleincome regions. While incidence and mortality rates are highest in developing countries, the accessibility to screening and treatments is limited in those regions. High dose rate (HDR) brachytherapy (BT) is part of the standard of care recommended for locally advanced cervical cancer. Commercial applicators for combined intracavitary-interstitial (IC/IS) BT treatments are very expensive and only offer fixed IS needle positions and orientations. The Montreal split ring (MSR) applicator modifies the CT/MR split-ring IC applicator by the addition of Adaptiiv caps, 3D printed at low cost with stereolithography apparatus (SLA) technology in biocompatible and sterilizable resin in order to allow integration and optimization of up to 10 IS trajectories. In this study, a new generation of caps reduces the diameter of the MSR applicator by at most 8.4 mm and introduces four additional IS needle positions inside the split ring (SR), two positions per SR. These caps are 3D printed using BioMed Clear resin on the Form3B (Formlabs Inc., Massachusetts, USA) SLA printer and accommodate up to 45° IS needle angles. The errors on the IS needle trajectories of the MSR applicator with the new caps are evaluated in a gynecological (GYN) phantom, developed within the framework of this project, and compared in a statistical analysis to the performance of the Venezia applicator (Elekta, Stockholm, Sweden). The developed GYN phantom includes an implantable silicone structure, optimized according to the feedback of two radiation oncologists specialized in GYN BT to simulate clinical implants insertion, which can support a large number of IS needles. The study on this phantom showed that the performance of one of the caps from the new generation does not present a statistically and clinically significant difference with the Venezia applicator. The performance of this cap is reproducible in different silicone media and using different IS needle types.

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3D printing technology, which has its origins in rapid prototyping, is increasingly used to build functional devices. Although 3D printing technology has been well developed for thermoplastic polymers and metals, it is still in the research phase for soft polymeric materials such as silicones. Silicones are an industrially vital polymer characterized by a broad spectrum of chemical and physical properties for several smart applications, including on skin printing, smart sensors, multigradient material, and soft actuators. Extrusion-based multimaterial printing is one of the 3D printing techniques that have been adapted due to its compatibility to process silicone-based materials for constructing various functional devices. However, there are several challenges such as achieving on the fly mixing at low Reynolds numbers regime, achieving fast switching while using Newtonian/non-Newtonian inks, and achieving multimaterial printing on nonplanar surfaces. The development of suitable and robust printheads that are able to tackle those challenges can expand the application of this technology to a wide range of fields. In this thesis, several deposition-controlled printhead designs have been created for 3D printing multifunctional devices using an understanding of microfluidics. The established printhead can be controlled to formulate different multigradient structures through on the fly mixing during the material printing. Moreover, the developed printhead can be adapted to print multi viscous inks with high switching rates up to 50 Hz. Through the developed system, the printhead was able to track topologies in real-time, allowing objects to be printed over complex substrates. These new capabilities were applied to fabricate functional structures in order to demonstrate the potential of the developed printhead approaches that can be used in various applications, including smart sensors, soft robotics and multigradient objects. / Thesis / Doctor of Philosophy (PhD) / 3D printing techniques, such as extrusion-based multimaterial printing, have recently been utilized to process silicones due to their versatility in different smart applications, including multigradient material and soft actuators. Although it represents significant progress, there are still several challenges, including the proper mixing during printing with a laminar flow regime, the fast switching between different inks, and the printing over complex topographies. Therefore, various printhead designs have been developed in this thesis to tackle these challenges. In particular, a mixer printhead has been designed to allow mixing during printing for building multigradient objects. Also, a scalable printhead has been developed to allow fast switching for creating pixelated structures. Finally, a simple mechanical system has achieved multimaterial printing over various nonplanar surfaces. To the best of the author's knowledge, the developed printheads can be used in many fields, such as soft robotics and smart devices.

Characterization of 3D printed polyester scaffolds modified by nano-hydroxyapatite for bone tissue engineering

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