A hybrid biomimetic nanomatrix composed of electrospun polycaprolactone and bioactive peptide amphiphiles for cardiovascular implants

Current cardiovascular therapies are limited by the loss of endothelium, restenosis and thrombosis. The goal of this study was to develop a biomimetic hybrid nanomatrix that combined the unique properties of electrospun polycaprolactone (ePCL) nanofibers with self-assembled peptide amphiphiles (PAs). ePCL nanofibers have interconnected nanoporous structures, but are hampered by a lack of surface bioactivity to control cellular behavior. It has been hypothesized that PAs could self-assemble onto the surface of ePCL nanofibers and endow them with the characteristic properties of native endothelium. The PAs, which comprised hydrophobic alkyl tails attached to functional hydrophilic peptide sequences, contained enzyme-mediated degradable sites coupled to either endothelial cell-adhesive ligands (YIGSR) or polylysine (KKKKK) nitric oxide (NO) donors. Two different PAs (PA–YIGSR and PA–KKKKK) were successfully synthesized and mixed in a 90:10 (YK) ratio to obtain PA–YK. PA–YK was reacted with pure NO to develop PA–YK–NO, which was then self-assembled onto ePCL nanofibers to generate a hybrid nanomatrix, ePCL–PA–YK–NO. Uniform coating of self-assembled PA nanofibers on ePCL was confirmed by transmission electron microscopy. Successful NO release from ePCL–PA–YK–NO was observed. ePCL–YK and ePCL–PA–YK–NO showed significantly increased adhesion of human umbilical vein endothelial cells (HUVECs). ePCL–PA–YK–NO also showed significantly increased proliferation of HUVECs and reduced smooth muscle cell proliferation. ePCL–PA–YK–NO also displayed significantly reduced platelet adhesion compared with ePCL, ePCL–PA–YK and a collagen control. These results indicate that this hybrid nanomatrix has great potential application in cardiovascular implants.