Riboflavin photo-cross-linking method for improving elastin stability and reducing calcification in bioprosthetic heart valves

Xenotransplantation. 2019 Mar;26(2):e12481. doi: 10.1111/xen.12481. Epub 2019 Jan 4.


Background: Glutaraldehyde cross-linked bioprosthetic heart valves might fail due to progressive degradation and calcification.

Methods: In this study, we developed a new BHVs preparation strategy named as "HPA/TRA/FMN" that utilized 3,4-hydroxyphenylpropionic acid (HPA)/tyramine (TRA) conjugated pericardium and riboflavin 5'-monophosphate (FMN) initiated photo-cross-linking method. HPA/TRA-pericardium conjugation would provide extra phenol groups for FMN initiated photo-cross-linking.

Results: The feeding ratio of riboflavin 5'-monophosphate was optimized. The collagenase and elastase enzymatic degradation in vitro, biomechanics, calcification, elastin stability in vivo, and macrophage marker CD68 were characterized. We demonstrated that riboflavin photo-cross-linked pericardiums had great collagen and elastin stability, improved mechanical properties, better resistance for calcification, and less CD68 positive macrophages in rat subdermal implantation study.

Conclusions: This new riboflavin photo-cross-linking strategy would be a promising method to make BHVs which have better elastin stability, less calcification, and reduced inflammatory response.

Keywords: bioprosthetic heart valves; calcification; elastin stabilization; photocrosslinking; riboflavin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bioprosthesis
  • Calcinosis / immunology*
  • Cross-Linking Reagents*
  • Glutaral / immunology
  • Heart Valve Prosthesis*
  • Pericardium / immunology
  • Riboflavin / immunology*
  • Transplantation, Heterologous / methods


  • Cross-Linking Reagents
  • Glutaral
  • Riboflavin