Polyurethane (PU) is widely used as cardiovascular biomaterials due to its mechanical properties and good biocompatibility but the inherent blood compatibility of PU itself is not enough for more widespread application. Heparin, a representative anticoagulant, is clinically well used and is known to promote endothelialization through complexation with VEGF or bFGF as a growth factor, which are effective to proliferation and differentiation of endothelial cells. Peptides like YIGSR and RGD were also found to promote adhesion and spreading ECs and show the synergistic effect when both of them were used.
The PU (Polycarbonate urethane, Bionate 90A) matrices were fabricated by the electrospinning process and modified with diisocyanate PEG (polyethylene glycol, 1.0K). Then, heparin was covalently bound onto PU-PEG surface. The peptides (RGD and YIGSR) were immobilized onto aminated PU-PEG surface by EDC/NHS method. The content and the bioactivity of bound heparin were analyzed by toluidine blue assay and factor Xa chromogenic assay, respectively. The immobilized peptides were confirmed by amino acid analysis, following hydrolysis. Surface properties of the modified PU were characterized by SEM, AFM and static contact angle. In vitro fibrinogen adsorption and platelet adhesion test of the bound heparin were carried out. To evaluate EC adhesive property, HUVEC attachment and proliferation tests were investigated in vitro. Finally, in vivo endothelialization of the bioactive PU matrices was characterized using a canine model.
Our results represented that PU matrices were successfully modified with heparin and peptides for improved endothelialization. These bioactive PU matrices revealed higher HUVEC activities than unmodified PUs in vitro and in vivo. Therefore, hepain/peptide co-immobilized PU surfaces can be applied to EC-specific matrices, including new cardiovascular applications with long-term patency.