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.