Novel small-caliber vascular grafts with trimeric peptide for acceleration of endothelialization

Both rapid endothelialization and the prevention of intimal hyperplasia are essential to improve the patency of small-caliber vascular grafts (SCVGs). Using the peptide array based screening system, we identified the peptide CAG (cysteine-alanine-glycine), which has a high affinity for endothelial cells and a low adhesive property for smooth muscle cells (SMCs). In this article, we report an in vivo analysis of novel vascular grafts that were constructed with a biodegradable polymer (poly-ε-caprolactone [PCL]) containing CAG peptide. The novel SCVG, which measured 0.7 mm in diameter and 7 mm in length, was fabricated using the electrospinning technique. Carotid arterial replacement was performed on Sprague-Dawley rats using SCVGs with (group CAG) or without CAG (group C). Histologic and biochemical assessments were performed at 1, 2, and 6 weeks after implantation. The ratio of endothelialization was significantly higher in group CAG compared with group C (CAG versus C, 64.4 ± 20.0% versus 42.1 ± 8.9% at 1 week; p = 0.017; 98.2 ± 2.3% versus 72.7 ± 12.9% at 2 weeks; p = 0.001; and 97.4 ± 4.6% versus 76.7 ± 5.4% at 6 weeks; p < 0.001). Additionally, Western blot analysis showed that the level of endothelial nitric oxide synthase (eNOS) at 1 week in group CAG was significantly higher than that in group C (CAG versus C, 1.20 ± 0.37 versus 0.34 ± 0.16; p = 0.013), and that α-smooth muscle actin (ASMA) at 6 weeks in group CAG was significantly lower than that in group C (CAG versus C, 0.89 ± 0.06 versus 1.25 ± 0.22; p = 0.04). The graft with CAG promoted rapid endothelialization and the potential for inhibition of intimal hyperplasia.