Native endothelium mimicking nanomatrices and applications

Cardiovascular disease is a major cause of death worldwide and, to improve vascular grafting and stents, scientists are turning to nanotechnology. While synthetic grafts are useful in many artery bypass surgery cases, grafts are prone to thrombosis due to platelet adhesion and intimal hyperplasia due to smooth muscle proliferation. Stenting closed arteries is also a widely used treatment; however, stents also cause injury to the artery and can cause similar types of thrombosis and hyperplasia as grafts. The lack of endothelialization of grafts and stents is a major limitation of these implants, and nanotechnology may provide several strategies to overcome this deficit. Since the native extracellular matrix consists of nanofibers, it is not surprising to find that studies show nanotopographical cues such as grooves smaller than 800 nm are more favorable to endothelial cell growth than larger features. For vascular grafting, electrospinning shows great promise as a method that produces strong nanofibrous material from a number of different polymers that can support numerous types of cells. Bioactivity can be increased by functionalizing materials with peptide ligands such as fibronectin-derived Arg-Gly-Asp (RGD), and laminin-derived Tyr-Ile-Gly-Ser-Arg (YIGSR), and by releasing “endothelium-derived relaxation factor” nitric oxide. Bare metal stents have been modified by coating with polymers that release anti-proliferative drugs to inhibit smooth muscle growth causing intimal hyperplasia, such as sirolimus and paclitaxel, to prevent restenosis of the artery. One coating, polyvinylidenefluoro-hexafluoropropylene, also supports the growth of endothelial cells. A recently introduced strategy uses peptide amphiphile self-assembling nanofibers to coat electrospun nanofibers or bare metal stents with nanofibers that include the fibronectin ligand RGD, laminin ligand YIGSR, or poly-lysine peptides reacted to NO, to provide nanotopographical cues, bioactive ligands, and drug-elution to the cardiovascular implants. Multi-functional approaches are possible to creating cardiovascular grafts and stents that mimic vascular native endothelium, and the next generation of devices have great potential to solve the problems of current cardiovascular implants.