Dr Nasir Ali Shah1,2, Professor Zoltan Endre1,2, Professor Tracie Barber3, Dr. Blake Cochran4, Dr. Jonathan Erlich1,2
1School of Clinical Medicine, Faculty of Medicine & Health, UNSW Sydney, Sydney, Australia, 2Department of Nephrology, Prince of Wales Hospital, Randwick, Australia, 3School of Mechanical and Manufacturing Engineering, Faculty of Engineering, UNSW Sydney, Sydney, Australia, 4School of Biomedical Sciences, Faculty of Medicine & Health, UNSW Sydney, Sydney, Australia
Biography:
I am a renal physician at the Prince of Wales Hospital and The Sutherland Hospital in Sydney. I have broad interests across general nephrology, including chronic kidney disease, and dialysis vascular access. As a PhD candidate at UNSW Sydney, my research focus is vascular biology and engineering. My PhD uses innovative 3D models based on patient-specific vascular geometries. By combining additive manufacturing with established biological techniques, I hope to better understand endothelial cell biology and their role in arteriovenous fistula maturation and cardiovascular complications.
Aim:
Develop a patient-specific macrofluidic model of arteriovenous fistulas (AVF) that replicates vascular elasticity to investigate endothelial cell (EC) responses relevant to AVF maturation.
Background:
Chronic kidney disease affects >10% of adults worldwide, with more than 2.5 million people receiving kidney replacement therapy – a figure projected to double by 2030. Haemodialysis requires a functional AVF, however 40-60% of AVFs fail to mature, contributing to poor outcomes. Existing experimental models fail to accurately replicate human vascular physiology.
Methods:
Patient AVFs were imaged using ultrasound, digitally segmented to generate geometries and 3D-printed. Material properties were tuned to mimic vessel elasticity. Doppler recordings were used to recapitulate physiologically-relevant flow. Human dermal microvascular endothelial cells were cultured on the luminal surface of constructs under static and flow conditions, and subsequently analaysed by immunofluorescence microscopy.
Results:
Macrofluidic models replicated patient-specific geometries with tunable vascular compliance (0.6 – 8.3% expansion from baseline) under pulsatile flow – consistent with physiologic vessel elasticity (6.39 +/- 1.3%). ECs were successfully maintained under static and flow conditions for up to 5 days. After 24 h of continuous flow (100 mL/min), ECs demonstrated shear-responsive remodelling when compared to those grown under static conditions (circularitry 0.74 +/- 0.16 vs. 0.48 +/- 0.11, p <0.0001 ; eccentricity 0.79 +/- 0.11 vs. 0.96 +/- 0.03, p <0.0001).
Conclusions:
Patient-specific macrofluidic platforms replicate native vascular biomechanical conditions offering a physiologically relevant system to study EC behaviour. This addresses key limitations of conventional in vitro and animal models and represents a promising tool to investigate EC biology underlying AVF maturation with the potential to inform development of targeted interventions to improve patient outcomes.