Enhanced Patency and Endothelialization of Small-Caliber Vascular Grafts Fabricated by Coimmobilization of Heparin and Cell-Adhesive Peptides.

The clinical utility of a small-caliber vascular graft is still limited, owing to the occlusion of graft by thrombosis and restenosis. A small-caliber vascular graft (diameter, 2.5 mm) fabricated by electrospinning with a polyurethane (PU) elastomer (Pellethane) and biofunctionalized with heparin and two cell-adhesive peptides, GRGDS and YIGSR, was developed for the purpose of preventing the thrombosis and restenosis through antithrombogenic activities and endothelialization. The vascular grafts showed slightly reduced adhesion of platelets and significantly decreased adsorption of fibrinogen. In vitro studies demonstrated that peptide treatment on a vascular graft enhanced the attachment of human umbilical vein endothelial cells (HUVECs), and the presence of heparin and peptides on the graft significantly increased the proliferation of HUVECs. In vivo implantation of heparin/peptides coimmobilized graft (PU-PEG-Hep/G+Y) and PU (control) grafts was performed using an abdominal aorta rabbit model for 60 days followed by angiographic monitoring and explanting for histological analyses. The patency was significantly higher for the modified PU grafts (71.4%) compared to the PU grafts (46.2%) at 9 weeks after implantation. The nontreated PU grafts showed higher levels of α-SMA expression compared to the modified grafts, and for both samples, the proximal and distal regions expressed higher levels compared to the middle region of the grafts. Moreover, immobilization of heparin and peptides and adequate porous structure were found to play important roles in endothelialization and cellular infiltration. Our results strongly encourage that the development of small-caliber vascular grafts is feasible.

Surface graft polymerization of poly(ethylene glycol) methacrylate onto polyurethane via thiol-ene reaction: preparation and characterizations.

A new surface modification that facilitates the grafting of poly(ethylene glycol) methacrylate (PEGMA) on a polyurethane (PU) surface was developed using a thiol-ene reaction. The thiolated PU surface for the grafting of PEGMA was created by fabricating allylated PU through an allophanate reaction, which was then modified with tetra-thiols to enhance the functionality of the PU surface. The amount of thiol groups increased with increasing irradiation time, and its concentration was almost equilibrated after 30 min irradiation. ESCA spectra revealed new two peaks on the thiolated PU surface at 163 and 228 eV, which was assigned to sulfur, and a significant increase in the oxygen content of the poly(PEGMA)-grafted PU was shown as compared with the other groups. Also, the irradiation time-dependent increase in the surface wettability of poly(PEGMA)-grafted PU was confirmed by contact angle measurement. These surface characteristics support that poly(PEGMA)-grafted PU was successfully prepared using a thiol-ene reaction. For in vitro protein adsorption and cell proliferation tests, the poly(PEGMA)-grafted PU surface showed repellent properties against both fibrinogen and smooth muscle cells, compared to other groups. This surface graft polymerization of PEGMA on a PU surface via a thiol-ene reaction can be used as a promising surface modification for improving blood compatibility of PU-based blood-contacting devices.

RGD peptide-immobilized electrospun matrix of polyurethane for enhanced endothelial cell affinity.

An Arg-Gly-Asp (RGD) peptide-immobilized electrospun matrix of polyurethane (PU) was developed for the enhanced affinity of endothelial cells (EC). The novel PU matrix was fabricated as a vascular shape using the electrospinning technique. Then, poly(ethylene glycol) (PEG) was immobilized on the porous PU matrix as a spacer, followed by conjugating RGD peptide to the amino end group of the PEG chain. In the proliferation test of human umbilical vein endothelial cells (HUVEC) on the modified PU matrix, the RGD-immobilized porous matrix showed enhanced viability of HUVEC as compared with an unmodified surface, demonstrating that the presence of RGD peptide promoted HUVEC proliferation. In addition, the RGD-immobilized PU porous matrix revealed higher cell viability than the RGD-immobilized PU film because of the porous structure with higher surface area, indicating an advantageous property of the porous matrix for HUVEC proliferation.