Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia, making the study of small vessel hemodynamics vital for advancing diagnostic and therapeutic strategies. This research focuses on fabricating microfluidic devices that replicate the lateral lenticulostriate arteries (LSA) to validate computational flow models of small cerebral vessels. A key challenge in studying CSVD is the lack of experimental validation for computational fluid dynamics (CFD) models, which are widely used to simulate hemodynamics. To address this, additive masked Stereolithography (mSLA) was employed to fabricate a microfluidic model of the LSAs. The study explored the impact of orientation, exposure time, and layer height on the roundness and error of the intended area of printed micro-pores, to optimize the manufacturing of a microfluidic device. The smallest printed pore measured 270 μm in diameter. Pores printed at a larger angle as assessed from the build plate were more likely to remain open, but exhibited a larger decrease in area compared to smaller angles. A lower exposure time exhibited a larger pore area, whereas a larger layer height showed a decrease in area from intended. The layer height and angle did not influence the roundness, whereas an increase in exposure time decreased the roundness of the pores. Additionally, flow experiments were conducted using a 3D printed microfluidic device to compare empirical data with CFD and analytical simulations. The encountered resistance was larger for the experimental results (3.19 ⋅10^11 Pa⋅s/m^3) compared to the analytical result (1.96 ⋅10^11 Pa⋅s/m^3) and the computational result (1.90 ⋅10^11 Pa⋅s/m^3), likely due to deviation from the intended size. Finally, arterial microfluidic devices were printed and flow was induced to showcase their functionality. Achieving precise channel dimensions remains the primary challenge in mSLA printing due to cumulative dosage effects.
This research bridges the gap between computational modeling and experimental validation, providing a platform for studying cerebral microcirculation. The findings demonstrate the feasibility of using commercially available 3D-printed microfluidic devices to replicate small cerebral vessels. The outcomes of this study contribute to the advancement of vascular biomodeling, with implications for future clinical applications in stroke and neurovascular research.

This thesis describes an investigation of the deposition of Stellite 6 on SS316L stainless steel substrates using a Gas Metal Arc Welding (GMAW) based Wire Arc Additive Manufacturing (WAAM) system. The primary aim of this research was to optimize the deposition process with a focus on reducing heat input and understanding the development of residual stress, a critical factor in the performance of hardfacing materials. The project utilized a zigzag toolpath deposition strategy requested by adaptation from current manual operation, aiming to achieve low heat input while maintaining layer integrity.
The experimental methods involved finite element analysis (FEA) to simulate the deformation of the sample for a better understanding of the material thermo-mechanical responses to the zigzag deposition strategy used. The deformation simulation agrees with the measured deflection. The model, however, computed very large residual stresses. To have a better evaluation of the residual stress resulted from the deposition process, Incremental Central Hole Drilling (ICHD) method was used for residual stress analysis. Residual stresses were introduced in the samples by depositing one or two layers, with different clamping configurations. The measured residual stresses together with the observations noted during the experiments were analysed, compared, and discussed. The results show that double layer deposition can reduce residual stress gradients and provide a more stable stress profile along the thickness of the deposited layer. Furthermore, although single-sided clamping allowed for a higher freedom of thermal expansion and contraction during the deposition process, which leads to a more balanced stress distribution, it also increases deformation. Therefore, the use of uniform clamping during deposition of Stellite 6 should be implemented for actual application case. Additionally, depending on the desired thickness of Stellite 6, a multi-layer deposition strategy can be implemented to minimize residual stress build up.
The research concluded that defect-free Stellite 6 layers can be successfully deposited using the GMAW-based WAAM process. The residual stress measurement showed that preheating and reducing the thermal gradient can effectively reduce the residual stress within the deposited material. The obtained results can be helpful for the further development of automated toolpath generation and the integration of 3D vision control systems for more efficient and reliable WAAM processes.

Prostate cancer is the most frequently diagnosed type of cancer among males. Brachytherapy has become a common treatment for this disease. In this form of radiotherapy, sealed radiation sources are placed through a implant catheters inside the prostate. This treatment affects the tumor cells locally and reduces damage to healthy tissues. However, accessing all relevant areas is met by difficulties. Innovating brachytherapy instruments can overcome these challenges. These new instruments need to be tested in a lab environment before patient testing is allowed. Phantom models provide a good validation model for testing new medical instruments. The goal of this study is to design and develop a cancerous prostate phantom model which can be used to test newly developed instruments for brachytherapy.
A material study was conducted to find the best mechanically tissue-mimicking materials. The effects of different concentrations, varying volumes, coolant additive and dimethyl-sulfoxide additive on the Young's modulus of poly-vinyl alcohol was tested. Unconfined compression tests were performed after each freeze-thaw cycle for a total of 7 cycles. These results showed that poly-vinyl alcohol can form material which, based on its Young's modulus, can mimic prostate tissue and adipose tissue. An increase in poly-vinyl alcohol concentration, volume, coolant additive, dimethyl-sulfoxide additive and the number of freeze-thaw cycles were each found to increase the Young's modulus of the material.
Three cancerous prostate phantom models were made of poly-vinyl material with each a different stiffness value achieved by varying the poly-vinyl alcohol concentrations. A low Young's modulus for model 1, medium for model 2 and high for model 3. The poly-vinyl alcohol was solved in a mixture of distilled water:DMSO (10:90 ratio) to produce a transparent material. Each model included a prostate, urethra and surrounding adipose tissue. The models were surrounded by a transparent casing which included an opening and template for needle insertion at the front. A pubic bone was added to model 2 and 3 to simulate prostate blockage by this tissue. Model 1 and 2 did not achieve the transparency that was required. The transparency was found to be sufficient in model 3.
A needle insertion experiment was conducted to validate the prostate phantom models. An 18Gauge brachytherapy needle was inserted 13, 10 and 20 times in model 1, 2 and 3 respectively with a velocity of 5 mm/s. Mean peak forces, describing the force upon puncture of the prostate material, for model 1 (0.57 N) and 2 (3.54 N) were lower than multiple peak forces found in literature. The median peak force of model 3 (6.17 N) came close to the peak force found during in patients with prostate cancer (6.28 N) in the study of Podder et al. (2006). Higher Young's moduli values produced higher peak forces. The insertion force in the adipose tissue of the models was lower than the results found in literature.
This study has shown that poly-vinyl alcohol can function as an easily controlled tissue mimicking material. The material study created an overview of the effects of concentration, volume, coolant, DMSO and freeze-thaw cycles on the Young's modulus of poly-vinyl alcohol. An easy to manufacture cancerous prostate phantom model was made of poly-vinyl alcohol and DMSO. Model 3 developed in this project can function as a test model for newly developed instruments meant for brachytherapy.

Background. The past four decades, the problem of resistant bacteria has emerged. As a result of biofilm formation of (resistant) bacteria on the implant, more implant-associated infections (IAI) occurred. This has caused an increase in orthopaedic implant revisions, causing a high burden of disease. To overcome the rising problem of resistance, many studies have focused on new antibacterial agents, such as Ag, Cu, and Zn nanoparticles (NPs) incorporated on titanium (Ti6Al4V) implants. It is known they show antibacterial effects. It is, however, unknown what causes the antibacterial effects of these metals incorporated on titanium implants. This study aims to unravel the antibacterial mechanisms of titanium implants bearing Ag, Cu or Zn NPs behind the in vitro antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA).

Methods. To obtain an implant surface bearing Ag, Cu or Zn NPs; porous Ti6Al4V implants and solid Ti6Al4Nb discs were treated by plasma electrolytic oxidation (PEO). The PEO electrolyte consisted of calcium acetate, calcium glycerophosphate, and Ag, Cu or Zn NPs. The surface morphology was visualized by scanning electron microscopy (SEM) and its chemical composition by energy dispersive X-ray spectroscopy (EDS). All implant groups contained either Ag, Cu or Zn NPs and were tested on its antibacterial leaching activity against MRSA by a zone of inhibition experiment. In addition, the antibacterial effects as a result of contact killing were examined by a direct contact assay. Porous and solid surfaces were compared to reveal the differences in their contact killing properties. Moreover, the porous implants were incubated for 2 h and 24 h. Furthermore, the generation of reactive oxygen species (ROS) of the implant with and without inoculation of bacteria was measured by electron paramagnetic resonance (EPR) for forty minutes. ROS generation after inoculation with bacteria was tested in two ways: (1) the implant was placed in a solution of bacteria PBS after which ROS generation was directly measured in 100 mM DMPO, and (2) the implant with bacteria in BHI was incubated for 2 h after which the implant was placed in 100 mM DMPO to examine ROS generation of the implant with adherent bacteria.

Results. PEO processing resulted in four biofunctionalized groups: PT, PT+Ag, PT+Cu, and PT+Zn. The presence of Ag, Cu and Zn NPs was confirmed by SEM and EDS. The antibacterial leaching activity was only observed in PT+Ag. In addition, porous implants showed better contact killing properties than solid discs. All biofunctionalized groups were significantly different from a non-treated (NT) implant considering contact killing in 24 h. Moreover, ROS generation was observed in all biofunctionalized implants. However, solely PT+Cu was significantly different from a NT implant. Furthermore, the EPR results showed that bacteria generate ROS. In all biofunctionalized groups, however, ROS decreases when bacteria are added. In all groups, the ROS generation of adherent bacteria to the implants showed higher intensity than the ROS generation of bacteria in PBS in contact with the implant.

Conclusion. Antibacterial surfaces incorporated with Ag NPs show most antibacterial leaching effects, attributed to the ion release of Ag. Furthermore, it is assumed that direct contact killing of Cu is a cause of ROS generation of an implant bearing Cu NPs.

In recent years, more and more medical operations are done minimally invasive. Intervention radiology is a medical specialty which uses minimally invasive techniques to diagnose, or treat diseases. Instruments like needles and catheters are used by radiologists to enter the network of veins and arteries guided by image modalities. A complex treatment in the interventional radiology is the Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure. This treatment is developed for people who suffer from liver cirrhosis which are not eligible for liver transplantation. The problem which arise with a liver affected by cirrhosis is that it can not transmit enough blood. Without transplantation or a treatment this will eventually lead to death. During the TIPS procedure a connection is made between the right hepatic and the portal vein by a shunt. As a result, blood pressure reduction in the portal system since the blood can flow back to the right atrium of the heart, bypassing the liver.

The hardest part in a TIPS procedure is the intrahepatic puncture between the hepatic and portal vein. The interventional radiologist tries to enter the portal vein by puncturing a small stylet from the hepatic vein through the liver tissue. Due to cirrhosis the liver tissue is very stiff and stylet deflection will occur. To reduce the uncertainty of entering the portal vein, this thesis is focused on designing a stylet that is more stiff and able to steer. It is expected that the complexity of the procedure will be reduced and a higher hit rate to enter the portal vein will be achieved.\\
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The prototype of the steerable stylet has been evaluated through various experiments, a visibility test and with procedures in a test liver model. During these experiments the steering characteristics, the stiffness of the stylet, the maximum lateral forces exerted by the tip while steering, the influence of the stylet orientation and the visibility are obtained. Afterwards, an evaluation was done in a liver model, made of PVA, to determine whether the stylet is capable to reduce the complexity of the intrahepatic puncture step in the TIPS procedure.

With the prototype made in this graduation project, based on a steerable ablation needle, the complexity of the TIPS procedure is not reduced yet. The steerable stylet was not able to enter the portal vein. It was already hard to enter the right hepatic vein since the pre-bent stiffening cannula was adapted with a smaller angle which was necessary since the steerable stylet was too stiff to push through the pre-bent angle. According to this prototype, possibilities are shown to use a mechanical steering mechanism in instruments with a long thin shaft. The transmission in combination with the joint mechanisms fits within 1.3mm diameter, was able to bridge 60cm from distal end to proximal end and had only 4 components, the stylet, the rigid cannula, the key to fix the stylet to the rigid cannula and the transmission. By translating the stylet in a push or pull direction relative to the rigid cannula, steering angles could be achieved. With further research and development this steering mechanism must be able to steer the required amount of degrees without any extra components, is well visible with ultrasound, and is good resistant against lateral forces.

Expanded Criteria Donor (ECD) organs are being used more often in clinical setting. The regenerative ability of the organs might be able to restore the organ to full functionality ex vivo. For long term kidney stabilization, optimization and monitoring an organ incubator is preferable. However, it is unclear which available parts would work best in synergy. A Normothermic Machine Perfusion (NMP) setup and a Mathematical Windkessel Model were created as a first step in a larger project of prolonged preservation of ECD organs. While the current NMP setup was found adequate for academic research, it can only be used for simple studies using water. Several fundamental improvements need to be made before the setup can be used as a fully functioning NMP setup for kidneys. Key improvements would be the addition of a Windkessel and a different cardiac pump.

When sawing in bone for medical or medico-legal procedures, fine, airborne dust is produced (aerosols) that can pose a health hazard when inhaled by practitioners. The goal of the current study was to find the influence of saw blade frequency and saw blade contact load, the degree of skeletonisation of the bone, the test environment with external air flows such as ventilation systems, and the type of saw blade used on the production of aerosol particles. A custom test setup was designed and manufactured to test the sawing parameters in 8 experiments, with 2 to 9 experimental conditions tested in each, where a particle counter was used to determine the production of aerosol particles while varying the 5 chosen parameters. Results showed that the number of counted particles was highest with higher saw blade frequencies, lower saw blade contact loads, in dry completely skeletonised bone compared to fresh bone, and using an electrical oscillating saw compared to hand-sawing. Under all conditions, the high amount of aerosol counted posed potential health risks. The tested external ventilation system was adequate in removing the produced number of particles, but these high-tech systems are not always available in developing countries or emergency situations. In conclusion, the production of aerosols can be reduced by optimising the sawing parameters. However, even the lowest number of aerosol particles counted during the current study was high enough to cause potential health risks to practitioners. Safety precautions should be taken, such as external ventilation, proper breathing gear, and adequate protocols, to truly minimise the risk in all bone sawing scenarios.