Exogenous hyaluronic acid and chondroitin sulfate crosslinking treatment for increasing the amount and stability of glycosaminoglycans in bioprosthetic heart valves.

Glutaraldehyde (GLUT) crosslinked bioprosthetic heart valves (BHVs) might fail due to progressive degradation and calcification. GLUT cannot stabilize glycosaminoglycans (GAGs), which are important for BHVs' life time. In this current study we developed a new BHVs preparation strategy using exogenous hyaluronic acid (HA)/chondroitin sulfate (CS) supplement and sodium trimetaphosphate (STP) crosslinking method. Exogenous HA and CS provide additional GAGs for pericardiums. STP could link two GAGs by reacting with hydroxyl groups in GAGs' repeating polysaccharides units. The feeding ratios of HA/CS were optimized. The GAGs content and long-term stability in vitro, biocompatibility, the in vivo GAGs stability and anti-calcification potential of GLUT/HA/CS and STP treated pericardiums were characterized. We demonstrated that GLUT/HA/CS and STP treated pericardiums had sufficiently increased GAGs' amount and stability and decreased calcification. This new exogenous hyaluronic acid/chondroitin sulfate supplement and sodium trimetaphosphate crosslinking strategy would be a promising method to make BHVs with better structural stability and anti-calcification properties.