Fibronectin-Hepatocyte Growth Factor Enhances Reendothelialization in Tissue-Engineered Heart Valve

Abstract

To overcome the limitations of tissue-engineered heart valves, which require cell seeding before implantation, a growth factor for in situ recellularization may be an important strategy. We developed a new decellularized valve containing a fusion protein combined fibronectin and hepatocyte growth factor. Here, we tested the hypothesis that our valve might accelerate in situ recellularization by inducing the proliferation of endothelial cells. Porcine aortic valves were decellularized using detergent. Fibronectin-hepatocyte growth factor was introduced into the decellularized valves. The decellularized valves with fibronectin-hepatocyte growth factor were implanted into the pulmonary arterial trunk of dogs (F group: n = 15). As controls, decellularized valves without the growth factor (C group: n = 12), and with hepatocyte growth factor (H group: n = 12) were implanted in the same manner. Histologic examinations were performed 1 week and 1 month after implantation. One week after implantation, endothelial cells partially covered the surface of the graft in the F group but not the C and H groups. Although the C and H groups had inadequate recellularization 1 month after implantation, the F group showed a monolayer of endothelial cells, underneath which were areas of additional cell layers, which were vimentin positive. Quantitative evaluation demonstrated the amount of vimentin in the F group was 71% of the native control, and it was much lower in the other groups (C, 2.8%; H, 16.8%) 1 month after implantation. This study demonstrated that fibronectin-hepatocyte growth factor enhanced early in situ recellularization in decellularized valves.