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Abstract: SA-PO004

In the Same Vein: Developing a Novel In Vitro Flow Model for Endothelium Using 3D-Printed, Patient-Specific Arteriovenous Fistulas

Session Information

Category: Bioengineering

  • 400 Bioengineering

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

Endothelial cell dysfunction is a feature of several medical conditions including chronic kidney disease (CKD). The global prevalence of advanced CKD (Stage 3-5) is approximately 8%, affecting an estimated 850 million people worldwide. For patients with end stage kidney disease treated with hemodialysis, easy vascular access is best achieved using a surgically-created arteriovenous fistula (AVF). Why some AVFs fail to mature while others develop high blood flow is unclear. Standard cell culture provides valuable insight into the role of endothelial cells in this process, but the flat surface neglects the complex physiology of disturbed blood flow through intricate vessel geometries. The use of animal models is limited by the ethical implications of the required interventions, the necessary surgical skill, an inability to simulate relevant comorbidities, differences in vessel size, breed genetic diversity, and limited commercially available reagents. The aim of this study was to use 3D-printing to create patient-specific models of arteriovenous fistulas for use in vascular research.

Methods

Patient AVFs were imaged using a modified ultrasound device. Specialised segmentation software generated AVF geometries which were 3D-printed using a water-soluble filament. Prints were cast in silicone and dissolved away leaving an AVF-shaped cavity. Human dermal microvascular endothelial cells (HMEC-1) were cultured on the internal surface of these models. Closed circuit hemodialysis tubing was then used to expose the endothelial cells to varying magnitudes of continuous flow.

Results

Fabrication of patient-specific models was accurate and reproducible. Immunofluorescence with DAPI and Phalloidin confirmed an HMEC-1 monolayer on the luminal surface. The endothelial cell monolayer was maintained after exposure to continuous flow over a 24-hour period. HMEC-1 cells exposed to flow polarized in the direction of flow as judged by alignment of the actin cytoskeleton.

Conclusion

Our 3D in vitro model overcomes limitations of current cell culture techniques whilst maintaining the 3D geometry only seen in humans and animal models. This will allow rapid investigation of endothelial cell signalling in true AVF geometries.