Abstract
The application of polyelectrolyte multilayer films is a new, versatile approach to surface modification of decellularized tissue, which has the potential to greatly enhance the functionality of engineered tissue constructs derived from decellularized organs. In the present study, we test the hypothesis that Heparin- vascular endothelial growth factor (VEGF) multilayer film can not only act as an antithrombotic coating reagent, but also induce proliferation of endothelial progenitor cells (EPCs) on the decellularized aortic heart valve. SEM demonstrated the adhesion and geometric deformation of platelets. The quantitative assay of platelet activation was determined by measuring the production of soluble P-selectin. Binding and subsequent release of heparin and VEGF from valve leaflets were assessed qualitatively by laser confocal scanning microscopy and quantitatively by ELISA methods. Human blood derived EPCs were cultured and the adhesion and growth of EPCs on the surface modified valvular scaffolds were assessed. The results showed that Heparin-VEGF multilayer film improved decellularized valve haemocompatibility with respect to a substantial reduction of platelet adhesion. Release of VEGF from the decellularized heart valve leaflets at physiological conditions was sustained over 5 days. In vitro biological tests demonstrated that EPCs achieved better adhesion, proliferation and migration on the coatings with Heparin-VEGF multilayer film. Combined, these results indicate that Heparin-VEGF multilayer film could be used to cover the decellularized porcine aortic valve to decrease platelet adhesion while exhibiting excellent EPCs biocompatibility.
Highlights
Heart valve disease remains a major medical problem of heart disease, and surgery offers good results for patients with advanced valvular heart disease
Morphology of decellularized porcine aortic valve (DPAV) and Polyelectrolyte multilayer (PEM)-DPAV Decellularization completely removed the cellular components of the porcine aortic heart valve leaflets (Fig. 1A, 1B)
The results demonstrated that valve coated with heparin-vascular endothelial growth factor (VEGF) multilayer can increase human endothelial progenitor cells (EPCs) migration, which is increased with the number of multilayer (Fig. 7, p,0.05)
Summary
Heart valve disease remains a major medical problem of heart disease, and surgery offers good results for patients with advanced valvular heart disease. Currently available heart valve prostheses have limitations, which are mainly related to life-long anticoagulation of mechanical valves and the degeneration of biological prostheses [1]. To overcome these limitations, a tissue engineered heart valve (TEHV), which is constructed by seeding cells on a valvular scaffold, might be a future option for valve replacement [2]. Decellularized allograft valves have already been shown with promising clinical results [3]. Clinical trials using decellularized xenogenic valves were catastrophic, with severe inflammation and fibrosis of the scaffold in vivo [4]. More recent clinical trials showed inconsistent results. Konertz W et al [5] supported the use of decellularized xenogenic valves as a viable alternative for right ventricular outflow tract (RVOT) reconstruction, while Perri G et al [6] suggested that the use of xenogeneic Matrix conduits should be considered with caution
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