Hybrid heart valves with VEGF-loaded zwitterionic hydrogel coating for improved anti-calcification and re-endothelialization

With the aging of the population in worldwide, valvular heart disease has become one of the most prominent life-threatening diseases in human health, and heart valve replacement surgery is one of the therapeutic methods for valvular heart disease. Currently, commercial bioprosthetic heart valves (BHVs) for clinical application are prepared with xenograft heart valves or pericardium crosslinked by glutaraldehyde. Due to the residual cell toxicity from glutaraldehyde, heterologous antigens, and immune response, there are still some drawbacks related to the limited lifespan of bioprosthetic heart valves, such as thrombosis, calcification, degeneration, and defectiveness of re-endothelialization. Therefore, the problems of calcification, defectiveness of re-endothelialization, and poor biocompatibility from the use of bioprosthetic heart valve need to be solved. In this study, hydrogel hybrid heart valves with improved anti-calcification and re-endothelialization were prepared by taking decellularized porcine heart valves as scaffolds following grafting with double bonds. Then, the anti-biofouling zwitterionic monomers 2-methacryloyloxyethyl phosphorylcholine (MPC) and vascular endothelial growth factor (VEGF) were utilized to obtain a hydrogel-coated hybrid heart valve (PEGDA-MPC-DHVs@VEGF). The results showed that fewer platelets and thrombi were observed on the surface of the PEGDA-MPC-DHVs@VEGF. Additionally, the PEGDA-MPC-DHVs@VEGF exhibited excellent collagen stability, biocompatibility and re-endothelialization potential. Moreover, less calcification deposition and a lower immune response were observed in the PEGDA-MPC-DHVs@VEGF compared to the glutaraldehyde-crosslinked DHVs (Glu-DHVs) after subcutaneous implantation in rats for 30 days. These studies demonstrated that the strategy of zwitterionic hydrogels loaded with VEGF may be an effective approach to improving the biocompatibility, anti-calcification and re-endothelialization of bioprosthetic heart valves.

Automated summary

With the aging population, valvular heart disease has become a major threat to human health. The current bioprosthetic heart valves prepared with xenograft or glutaraldehyde crosslinking have limitations such as thrombosis and calcification. In this study, hydrogel hybrid heart valves with improved anti-calcification and re-endothelialization were prepared using decellularized porcine heart valves and zwitterionic monomers. The results showed that the hydrogel-coated hybrid heart valve exhibited excellent collagen stability, biocompatibility, and re-endothelialization potential, with less calcification deposition and immune response compared to the glutaraldehyde-crosslinked heart valve.