Each year in the Netherlands almost two thousand people are diagnosed with End Stage Kidney Disease, amounting to a total of 7 million people worldwide. With an insufficient amount of donors available, most of these patients are treated using haemodialysis where the blood is filtered with a dialysis machine. Prior to this treatment an arteriovenous fistula (AVF) or arteriovenous graft(AVG) is created to increase their blood flow sufficiently to speed up the filtration process. Another result of increasing the blood flow is the size increase of the vein, leading to easier access. Unfortunately, the continuous high flow rate is linked to various negative effects. To counter these negative effects a Dynamic Arteriovenous System (DAS) or dynamic AVF (dAVF) was developed that can regulate the flow on demand. This allows for the flow to be increased temporarily during dialysis and to return to nominal values outside of dialysis with the ultimate goal of increasing life expectancy. Earlier iterations of the dAVF encountered reliability issues due to the formation of fibrous tissue on critical locations of the implant hindering actuation on the anastomosis. For this project, a compliant implantable dAVF-Valve is developed that minimizes the influence of ingrowth and provides a more robust solution.

This thesis project is part of a larger research project at the LUMC and focuses on overcoming challenges in studying blood vessel mechanics, particularly disturbed flow conditions, using Gelatin Methacryloyl (GelMA). Traditional models fail to replicate the complexity of blood vessels. GelMA stands out for its adjustable mechanical properties, such as stiffness and elasticity, closely mimicking natural blood vessels. It supports cell growth, which is vital for modelling blood vessels realistically. The current gap in research lies in the accurate representation of the mechanical environment of blood vessels, limiting our understanding of vascular diseases like atherosclerosis. Improvements are needed in flow models to replicate natural blood flow patterns and conditions such as bypasses or arteriovenous fistulas more accurately.
Goal
The development and validation of an improved GelMA disturbed flow model for in vitro validation of cell culturing under disturbed flow conditions.
Method
To determine the compressive modulus of the GelMA, three sets of samples are produced with different exposure times to UV light. These samples were subjected to compressive testing to determine the pressure/strain characteristics of the GelMA.
Furthermore, the disturbed flow model is partially newly designed. A new cover allows for incorporating a pressure sensor to determine if the model can operate under physiological pressure levels. To achieve this pressure, a pump with adjustable flow output is selected. Flowmeters were included in the test setup to determine when the correct flow was performed. The balance between the right pressure and flow results is described as the systemic vascular resistance of the disturbed flow model.
Results
The results of this study are the findings on the compressive modulus of the GelMA used for the research in the LUMC. The optimal curing time for achieving 10\%-15\% strain at physiological pressure levels (80-120 mmHg) was identified as 150 seconds, indicating a clear relationship between curing duration and GelMA's mechanical properties. The disturbed flow model improved the mean pressure to 113 mmHg, showing a more consistent pattern but with systolic pressure exceeding the desired range. Placing the sensor directly on the disturbed flow model improved results, suggesting potential improvements over the current IBIDI pump system waveform. The experiment targeted a total flow of 12 ml/min, similar to earlier experiments. It prevented cells from washing away from the GelMA substrate, with a split between inlets and outlets of 15\%-85\%. Initial runs used syringes for flow measurement, achieving a total flow of 11.8 ml/min, with a split of 1.8 ml/min and 10 ml/min, matching the desired split. With a pressure of 113 mmHg and total flow of 11.8 ml/min, the calculated total system resistance is 9.58 mmHg*min*mL-1 Peripheral Resistance Units (PRU), equivalent to 766 dynes*sec*cm-5 in cgs units.
Conclusion
This project successfully determined GelMA's possibilities in creating advanced in vitro vascular models, particularly under disturbed flow conditions. Through experimentation, GelMA demonstrated the ability to mimic native blood vessels' mechanical properties, offering improvements for future vascular research. Optimal conditions for GelMA were identified with a curing time of 150 seconds, resulting in a strain of 10\%-15\% under physiological pressures (80-120 mmHg). The fluidic test setup closely approached physiological pressures and allowed for two pathways resembling arteriovenous fistula (AVF) or bypass conditions. The correct flow of 12 ml/min and a split of 15\%-85\% was achieved. Determining systemic vascular resistance (SVR) contributes to setting up future experiments quicker and accurately within desired parameters.

Background: Kidney failure, also called end-stage renal disease, means the kidney has lost its function to remove waste from the blood. Patients with kidney failure usually need hemodialysis, which uses a machine to replace the function of a healthy kidney, to keep them alive and prolong their lives. In order to begin hemodialysis, it is crucial to prepare vascular access, which is a location in your body from which blood can be drawn and then returned at a high rate. People have found that the traditional ways of achieving vascular access will lead to a series of complications. So the newly designed Dynamic Arteriovenous system (DAS), which can control the opening and closing of the arteriovenous graft, was designed to solve the problem. Since the DAS is implanted under the skin of the human arm, it is hard for the operator to observe the status of the graft, so a monitoring system that can detect the graft status is needed.Objective:The goal of the research is to deisgn and evaluate a monitoring system for detecting the graft status of the DAS.Method: To solve the research problem, four sub-questions are proposed and solved to achieve possible concepts for the design. A Harris profile with grading criteria is set up to compare and determine the final concept to be developed. After building a test set-up for the final design, the design's effective range, accuracy, size, mass, usability, and detection success rate are evaluated. Results: The final design of the monitoring system consists of three sensors outside the body and two magnets in the DAS. The three sensors react to the position change of the magnets in the DAS and determine the relative position of the DAS under the skin and the status of the graft with the help of a User Interaction Interface. Through in-vitro tests, it is evaluated that the design meets most of the requirements and can be further developed if proper components are chosen and in-vivo tests are done. Conclusion: A relatively complete concept of the monitoring system and the corresponding User Interaction Interface are designed. Through a series of tests, it is believed to have the potential to be further developed and be useful to the DAS. In-vivo tests must be done to evaluate the system's biocompatibility before the clinical appliance.

The goal of this Thesis is to reduce the patient's discomfort during hemodialysis by achieving improved vascular access using a novel insertion device with a dilating diameter. High measures of discomfort are associated during achieving vascular access during hemodialysis therapy. The vascular access devices require large gauge sizes (14/15G) compared to the entry veins to achieve the high blood flow rates (BFRs) needed for an efficient dialysis. These large gauge sizes result in a moderate to severe pain experience for most dialysis patients during insertion. Moreover, the entered vein needs to be surgically prepared before it is able to withstand the used BFRs. A now commonly used technique to prepare the vein, is the creation of an Arteriovenous fistula (AVF). Although less than the techniques used in the past, an AVF can come with complications. An AVF can cause more narrow access veins due to maturation problems, which results in a higher chance of a miss hit and unnecessary trauma.

To reduce patients' discomfort associated with achieving vascular access, a design process was set up in order to reduce both the experienced pain as the possibility of miss hits. The size of the access device was said to be a major cause for both problems. Accordingly, there seems to be a need for a smaller insertion gauge without lowering the BFR. Based on this, a novel insertion device with a dilating diameter was designed.

A patent study was conducted of existing solutions for the design obstacles. The solutions found were combined with novel ideas not found during the patent study and consolidated in a morphological overview. This was used as a tool to choose and elaborate four concepts based on two dilation solutions: a dilating spiral and a slide-on dilator.

To validate the concepts two proof-of-principle experiments were executed for every dilation solution, resulting in four experiments in total. A difference in insertion force for adding a slide-on dilator compared to the conventional straight needles was measured. The slide-on dilator was found to produce a higher insertion force than the currently used needle and was therefore rated as more painful than the currently used insertion methods. As the dilating spiral is a new design, its working principle itself had to be proven during the experiment. The results showed how a dilating spiral, as designed in the concepts, is able to create sufficient dilation force.

The experimental results were used to rate the set-up criteria and choose one final concept. The concept was constructed and assembled, after which the design was validated by means of 3D printed parts and a larger scaled dilating spiral. The evaluation was incorporated into the final design, which in turn has been evaluated after it was assembled. All parts but the Spiral-Dilator were 3D-printed on a scale 1:1 and work well together. The device fits well in one's hand, feels naturally and is easy to handle. The Spiral-Dilator was created on a larger scale. Testing made clear that a twisting motion was necessary to let the spiral stay in shape during the slide back of its holder. To do so, the Slide Container has to be altered to enable the Dilation Slide slide back in a twisting motion. A final version of the Spiral-Dilator was not created and will be necessary for a definite confirmation of the working principle. Nonetheless, the Dilating Insertion Device (DID) has shown to be promising, it adds accuracy and in potential reduce experienced pain to the insertion for vascular access.