Endothelium-Protective, Intimal Hyperplasia-Resistant PCL/KAT Scaffold for Vascular Implants

Area of Science:

• Biomaterials Science
• Cardiovascular Research
• Regenerative Medicine

Background:

• Small-diameter vascular grafts (SDVGs) are crucial for cardiovascular disease treatment but face challenges like thrombosis and restenosis.
• Incomplete endothelium formation and abnormal smooth muscle cell proliferation hinder SDVG clinical success.
• Hydrogen sulfide (H2S) is a vital signaling molecule in the cardiovascular system, offering anti-inflammatory, anti-hyperplastic, and pro-angiogenic effects.

Purpose of the Study:

• To engineer an H2S-releasing vascular graft to improve SDVG performance.
• To investigate the graft's ability to promote endothelialization and modulate smooth muscle cell behavior.
• To evaluate the graft's efficacy in preventing thrombosis and restenosis in vivo.

Main Methods:

• Synthesis of a human hair keratin-based H2S donor.
• Co-electrospinning of the H2S donor with poly(ε-caprolactone) to create the vascular graft.
• In vitro assessment of endothelial cell (HUVEC) growth/migration and smooth muscle cell (HUASMC) proliferation.
• In vivo implantation studies to evaluate graft performance and tissue response.

Main Results:

• The H2S-releasing graft successfully promoted HUVEC growth and migration while suppressing HUASMC proliferation.
• The graft accelerated endothelium formation under shear stress and provided protection against oxidative stress.
• In vivo experiments showed complete endothelial regeneration without significant smooth muscle layer thickening after one month.

Conclusions:

• Keratin-based H2S-releasing vascular grafts offer a promising strategy for improving SDVG functionality.
• H2S release effectively modulates cellular responses, promoting tissue regeneration and preventing adverse remodeling.
• This approach provides a viable solution for enhancing the clinical applicability of small-diameter vascular grafts.