Approach for fabricating tissue engineered vascular grafts with stable endothelialization

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Vascular Biology

Background:

• Stable endothelialization of tissue engineered vascular grafts (TEVGs) remains a significant challenge for clinical application.
• Existing methods for seeding endothelial cells (ECs) onto scaffolds often result in poor mechanical stability under physiological flow.

Purpose of the Study:

• To develop and validate a novel approach for creating mechanically stable endothelial cell layers within TEVGs.
• To assess the viability, phenotype, and stability of endothelial cells treated with a poly(ethylene glycol) diacrylate (PEGDA) intercellular 'cementing' agent.

Main Methods:

• Fabrication of a bi-layered construct by bonding an EC layer, stabilized with PEGDA, to a tubular scaffold.
• Assessment of bovine aortic endothelial cell (BAEC) viability and expression of mature and injury-associated markers post-treatment.
• Evaluation of the mechanical stability of 'cemented' EC layers under high shear pulsatile flow compared to conventionally 'seeded' layers.

Main Results:

• The PEGDA 'cementing' process maintained high EC viability and expression of mature endothelial markers without significant induction of injury pathways.
• 'Cemented' EC layers demonstrated superior stability, remaining intact after 48 hours of pulsatile flow.
• Conventionally 'seeded' EC layers detached within 1 hour under identical flow conditions.
• The approach was successfully extended to include degradable PEGDA 'cements' that allow for cell elongation.

Conclusions:

• This study validates a novel method for fabricating bi-layered TEVGs with robust and stable endothelialization.
• The PEGDA 'cementing' technique offers a promising strategy to overcome the limitations of current TEVG endothelialization methods.
• The developed approach significantly enhances the mechanical stability of endothelial layers, crucial for TEVG functionality.