Abstract: SA-OR37
PRINTcision Medicine: A Reusable, Three-Dimensional-Printed, Patient-Specific, In Vitro Model of Arteriovenous Fistulas for Endothelial Cell Studies
Session Information
- Dialysis Vascular Access: Research Advances
October 26, 2024 | Location: Room 8, Convention Center
Abstract Time: 04:30 PM - 04:40 PM
Category: Dialysis
- 803 Dialysis: Vascular Access
Authors
- Shah, Nasir A., University of New South Wales School of Clinical Medicine, Sydney, New South Wales, Australia
- Endre, Zoltan, University of New South Wales School of Clinical Medicine, Sydney, New South Wales, Australia
- Barber, Tracie, University of New South Wales School of Mechanical and Manufacturing Engineering, Sydney, New South Wales, Australia
- Cochran, Blake, University of New South Wales School of Biomedical Sciences, Sydney, New South Wales, Australia
- Erlich, Jonathan H., University of New South Wales School of Clinical Medicine, Sydney, New South Wales, Australia
Background
Approximately 850 million people worldwide have CKD. For those with end stage kidney disease on haemodialysis, vascular access is best achieved using a native AVF. Though the molecular mechanisms underpinning AVF maturation are not well-established, endothelial cells appear to play a critical role in AVF maturation. Standard cell culture provides valuable insight into endothelial cell function, but the flat surface neglects the complex physiology of disturbed blood flow through intricate vessel geometries. We have developed and refined a macrofluidic model of AVFs using true patient geometries.
Methods
Patient AVFs were imaged using a modified ultrasound machine, digitally segmented to generate AVF geometries, and 3D-printed using a water-soluble filament. Prints were cast in silicone and dissolved leaving an AVF-shaped cavity. Human dermal microvascular endothelial cells (HMEC-1) were cultured on the internal surface of these models. Custom components were fabricated to create a flow circuit using autoclave-sterilisable materials. Patient-specific AVF doppler recordings were used to program a peristaltic pump.
Results
Immunofluorescence with DAPI and Phalloidin confirmed the presence of a HMEC-1 monolayer on the luminal surface of the patent-specific AVF models. Using autoclave sterilised components, the flow circuit ran for 10 days without bacterial contamination. Pulsatile flow was successfully achieved using the programmable peristaltic pump.
Conclusion
Our macrofluidic device overcomes many of the limitations of current cell culture techniques and animal models. By using patient-specific geometries, physiologic pulsatile flow, and running flow experiments over biologically relevant timelines, this novel in vitro model will facilitate investigation of endothelial cell biology under patient-relevant conditions.