A modular ex vivo human vessel perfusion platform for studying vascular reconstruction.
- 1Department of Surgery, University of Chicago, Chicago, IL.
- 2Department of Surgery, University of Illinois Chicago, Chicago, IL.
- 3Noninvasive Vascular Imaging Laboratories, University of Chicago Medicine, Chicago, IL.
Abstract
Background
Vascular tissue responses to mechanical and biochemical stimuli are central to many vascular diseases and interventions, including maturation and failure of arteriovenous fistulas (AVF). Experimental systems that preserve native human vascular architecture while allowing controlled perfusion, surgical manipulation, and vascular interventions remain limited. We developed a modular ex vivo perfusion platform that supports pulsatile flow across multiple vascular configurations and enables controlled study of vessel architecture, hemodynamics, and cell biology ex vivo.Methods
Deidentified human iliac arteries and veins discarded from liver transplantation were obtained under an Institutional Review Board-approved protocol and mounted in a closed-loop circuit driven by a pulsatile blood pump. Straight arterial vessels and surgically created ex vivo AVF were perfused with endothelial cell culture medium supplemented with 1× penicillin-streptomycin, maintained at 37 °C. Flow dynamics were assessed using Doppler ultrasound. Representative vessel segments were fixed for hematoxylin and eosin, Masson trichrome, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and cleaved caspase-3 immunohistochemistry. TUNEL-positive area was quantified across whole vessel sections using Fiji (ImageJ) with Otsu automated thresholding, with manual counts of TUNEL- and cleaved caspase-3-positive nuclei performed as confirmatory analyses.Results
The platform accommodated straight arterial and surgically constructed AVF configurations during 2-hour pump perfusion. Pump settings of 40 strokes/min and 7 mL stroke volume generated pulsatile perfusion, confirmed by pressure transducers. In straight arterial runs, pulsed-wave Doppler confirmed measurable flow through the isolated human iliac artery, with velocities ranging from 4.81 to 25.18 cm/s and a mean velocity of 18.9 cm/s. In the AVF configuration, Doppler ultrasound demonstrated disturbed flow at the anastomosis, and venous outflow volume-flow rates ranged from 752.1 to 1442.5 mL/min, exceeding the 600 mL/min threshold commonly used to define functional fistula flow. Histology demonstrated close arteriovenous apposition in the constructed fistula. Pre- and postperfusion TUNEL quantification showed no increase in TUNEL-positive area after 2-hour perfusion, whereas in a separate time-course analysis, TUNEL-positive area increased with longer intervals from vessel acquisition to fixation.Conclusions
We describe a modular human vessel perfusion platform that supports pulsatile flow and clinically relevant AVF conditions ex vivo. Histologic assessment demonstrated preserved vessel architecture and no increase in apoptotic burden after short-term pump perfusion. This system provides a biologically viable human tissue platform for studying mechanical, biochemical, and device-related contributors to vascular reconstruction.Clinical relevance
Pathologic vascular remodeling contributes to critical vascular conditions, including peripheral arterial disease, adverse surgical reconstruction outcomes, restenosis, and arteriovenous fistula failure. Current models often lack intact adult human tissue under controlled flow. This modular ex vivo perfusion platform preserves native vessel architecture while supporting pulsatile perfusion, surgical manipulation, Doppler ultrasound assessment, and histologic analysis. By enabling controlled study of adult human iliac arteries and veins across multiple configurations, this system may support future investigation of vascular remodeling mechanisms, device testing, therapeutic delivery, and clinically relevant hemodynamic responses before translation to patient care.
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BibTeX
@article{wood2026modular,
title = {{A modular ex vivo human vessel perfusion platform for studying vascular reconstruction.}},
author = {Chelsey T Wood and Marc Wahab and Kentaro Noda and Marybeth Georges and Samantha Kallivretakis and Nhung Nguyen and Ibrahim Khalil and Pablo G Sanchez and Luka Pocivavsek and Sara Gaines},
journal = {JVS-vascular science},
year = {2026},
month = sep,
doi = {10.1016/j.jvssci.2026.100445},
url = {https://europepmc.org/article/MED/42959873},
note = {CC BY},
}
RIS
TY - JOUR
TI - A modular ex vivo human vessel perfusion platform for studying vascular reconstruction.
AU - Chelsey T Wood
AU - Marc Wahab
AU - Kentaro Noda
AU - Marybeth Georges
AU - Samantha Kallivretakis
AU - Nhung Nguyen
AU - Ibrahim Khalil
AU - Pablo G Sanchez
AU - Luka Pocivavsek
AU - Sara Gaines
PY - 2026
DA - 2026/09/16
JO - JVS-vascular science
DO - 10.1016/j.jvssci.2026.100445
UR - https://europepmc.org/article/MED/42959873
AB - Background Vascular tissue responses to mechanical and biochemical stimuli are central to many vascular diseases and interventions, including maturation and failure of arteriovenous fistulas (AVF). Experimental systems that preserve native human vascular architecture while allowing controlled perfusion, surgical manipulation, and vascular interventions remain limited. We developed a modular ex vivo perfusion platform that supports pulsatile flow across multiple vascular configurations and enables controlled study of vessel architecture, hemodynamics, and cell biology ex vivo.Methods Deidentified human iliac arteries and veins discarded from liver transplantation were obtained under an Institutional Review Board-approved protocol and mounted in a closed-loop circuit driven by a pulsatile blood pump. Straight arterial vessels and surgically created ex vivo AVF were perfused with endothelial cell culture medium supplemented with 1× penicillin-streptomycin, maintained at 37 °C. Flow dynamics were assessed using Doppler ultrasound. Representative vessel segments were fixed for hematoxylin and eosin, Masson trichrome, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and cleaved caspase-3 immunohistochemistry. TUNEL-positive area was quantified across whole vessel sections using Fiji (ImageJ) with Otsu automated thresholding, with manual counts of TUNEL- and cleaved caspase-3-positive nuclei performed as confirmatory analyses.Results The platform accommodated straight arterial and surgically constructed AVF configurations during 2-hour pump perfusion. Pump settings of 40 strokes/min and 7 mL stroke volume generated pulsatile perfusion, confirmed by pressure transducers. In straight arterial runs, pulsed-wave Doppler confirmed measurable flow through the isolated human iliac artery, with velocities ranging from 4.81 to 25.18 cm/s and a mean velocity of 18.9 cm/s. In the AVF configuration, Doppler ultrasound demonstrated disturbed flow at the anastomosis, and venous outflow volume-flow rates ranged from 752.1 to 1442.5 mL/min, exceeding the 600 mL/min threshold commonly used to define functional fistula flow. Histology demonstrated close arteriovenous apposition in the constructed fistula. Pre- and postperfusion TUNEL quantification showed no increase in TUNEL-positive area after 2-hour perfusion, whereas in a separate time-course analysis, TUNEL-positive area increased with longer intervals from vessel acquisition to fixation.Conclusions We describe a modular human vessel perfusion platform that supports pulsatile flow and clinically relevant AVF conditions ex vivo. Histologic assessment demonstrated preserved vessel architecture and no increase in apoptotic burden after short-term pump perfusion. This system provides a biologically viable human tissue platform for studying mechanical, biochemical, and device-related contributors to vascular reconstruction.Clinical relevance Pathologic vascular remodeling contributes to critical vascular conditions, including peripheral arterial disease, adverse surgical reconstruction outcomes, restenosis, and arteriovenous fistula failure. Current models often lack intact adult human tissue under controlled flow. This modular ex vivo perfusion platform preserves native vessel architecture while supporting pulsatile perfusion, surgical manipulation, Doppler ultrasound assessment, and histologic analysis. By enabling controlled study of adult human iliac arteries and veins across multiple configurations, this system may support future investigation of vascular remodeling mechanisms, device testing, therapeutic delivery, and clinically relevant hemodynamic responses before translation to patient care.
SN - 2666-3503
ER -