Regeneration of acellularized porcine pulmonary valve in presence of fucoidan and VEGF: biological prosthesis construction ready for transplantation

Valvular heart disease is a worldwide public issue, since 280.000 surgeries on heart valves are performed every year. A current approach includes the application of porcine bio-prosthesis valves which have the potential for... [ view full abstract ]

Valvular heart disease is a worldwide public issue, since 280.000 surgeries on heart valves are performed every year. A current approach includes the application of porcine bio-prosthesis valves which have the potential for growth and regeneration and can be integrated as a vital part of the heart. The association of cell and molecular therapy in bioengineering could challenge their weaknesses in histocompatibility and durability. The acellularization of valves to improve biocompatibility leads to disrupt the structure of the extracellular matrix by deterioration of elastin, collagen fibers and glycosaminoglycans, decreasing the tissue elasticity.

Fucoidan, a marine glycosaminoglycan-mimetic, prevents intimal hyperplasia and induce re-endothelialization. As sulfated polysaccharide, fucoidan possesses comparable anti-thrombotic properties than heparin and bind to growth factor such as VEGF.
In the aim to improve the acellular valve regeneration, we coated the valves with 3 bilayers of VEGF-fucoidan solution and seeded endothelial cells on. Results showed that fucoidan was localized at the surface of tissue leading to increase cell adhesion and proliferation to the valves with high rate viability up to 7 days of culture. We observed a connective endothelium-like monolayer. Thrombogenicity assay with fresh blood performed in bioreactor demonstrated that the coating of acellulariezd valves with VEGF-fucoidan decreased the number of aggregated and activated platelets.

These results suggested that the coating with VEGF-fucoidan of acellularized valve improved their regenerative properties by increasing endothelial cells adhesion, proliferation and by reduction of thrombogenesis. Thus, VEGF-fucoidan treatment of valves is very attractive and promising tool to develop valves bio-prosthesis for clinical application.