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Engineering Biological-Based Vascular Grafts Using a Pulsatile Bioreactor
Published on: June 14, 2011
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Physiologically Modeled Pulse Dynamics to Improve Function in In Vitro-Endothelialized Small-Diameter Vascular Grafts
Joseph S Uzarski1, Jhon Cores1, Peter S McFetridge1
1J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida , Gainesville, Florida.
Tissue Engineering. Part C, Methods
|May 22, 2015
Summary
This study engineered functional vascular grafts by using a novel two-phase shear conditioning approach. Physiologically modeled pulse dynamics improved endothelial cell function, reducing occlusion risk in vascular bypass grafting.
Area of Science:
- Biomaterials Science
- Vascular Biology
- Tissue Engineering
Background:
- Small-diameter vascular grafts often fail due to intimal hyperplasia and thrombosis, stemming from a lack of functional endothelium.
- Endothelial cell (EC) conditioning using shear stress in bioreactors can promote a quiescent, non-thrombotic phenotype.
Purpose of the Study:
- To develop and evaluate a novel two-phase shear conditioning strategy to enhance endothelialization of vascular grafts.
- To compare the efficacy of physiologically modeled pulse dynamics (PMPD) versus constant frequencies (CF) in promoting a functional endothelial phenotype.
Main Methods:
- Decellularized human umbilical vein scaffolds were seeded with ECs using axial rotation.
- A flow-ramping paradigm adapted ECs to arterial shear stress and pressure.
- ECs were conditioned for 72 hours using either CF or PMPD in perfusion bioreactors.
Main Results:
- PMPD-conditioned grafts showed a more functional transcriptional profile compared to CF.
- PMPD significantly reduced EC metabolic activity (62.5% vs. 39.8% reduction).
- PMPD significantly increased nitric oxide production (80.42 vs. 48.75 nmol/10(5) cells).
Conclusions:
- In vitro manipulation of shear stress using PMPD promotes a quiescent endothelial phenotype on vascular grafts.
- This approach may inhibit graft failure mechanisms like cell adhesion and smooth muscle cell hyperplasia.
- Modulating bioreactor conditions offers a promising strategy to improve clinical outcomes for vascular bypass grafting.

