Klotho functionalization on vascular graft for improved patency and endothelialization.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Vascular Biology

Background:

• The Klotho (KL) gene is implicated in aging processes.
• Small-diameter tissue-engineered blood vessels (TEVs) face challenges with patency.
• Secreted Klotho (SKL) is a functional form of Klotho.

Purpose of the Study:

• To investigate if secreted Klotho (SKL) improves the patency of small-diameter TEVs.
• To determine if SKL enhances cell adhesion on tissue-engineered vascular grafts.
• To evaluate SKL's potential in creating substitutes for coronary artery bypass grafting.

Main Methods:

• Recombinant human SKL protein was produced.
• Acellular small intestinal submucosa (SIS) was cross-linked with heparin and SKL.
• Tissue-engineered vascular grafts were created and tested in vitro and in vivo in rabbits.

Main Results:

• SKL treatment promoted endothelial cell proliferation and adhesion.
• SKL upregulated Focal Adhesion Kinase (FAK) phosphorylation and RhoA.
• SKL-modified grafts showed improved patency, endothelialization, and smooth muscle regeneration in vivo.

Conclusions:

• SKL-modified SIS grafts effectively enhance the patency of small-diameter TEVs by improving cell adhesion.
• SKL holds significant potential for developing substitutes for coronary artery bypass grafting.
• This study highlights SKL as a key factor in advancing vascular tissue engineering.