Catechol-mediated and copper-incorporated multilayer coating: An endothelium-mimetic approach for blood-contacting devices

Abstract

Implantation of blood-contacting materials/devices usually causes severe thrombus formation, inflammatory reactions, excessive hyperplasia, and ultimately, induce endothelial dysfunction. In this work, a biomimetic approach was established to address those adverse problems through constructing a catechol-mediated and copper-incorporated multilayer coating. The biomimetics was mainly obtained via two paths. The first one was structure bionics, which used polyelectrolytes (heparin and polyethyleneimine) to modify with catechol moieties and then further formed a multilayer coating via layer-by-layer assembly, so as to mimic the mussel adhesive DOPA-rich structure; the second one was function bionics, which copper ions were then incorporated to function as the catalysts to decompose the endogenous S-nitrosothiols to release nitric oxide (NO), so as to mimic the key function of healthy endothelial cells. The quartz crystal microbalance with dissipation (QCM-D) was used to monitor the multilayer construction process and demonstrated the enhanced stability of the catechol-mediated multilayer coatings. Besides, the catechol-rich coating could also support the sustained release of heparin. Copper ions were incorporated into the multilayer coatings via the catechol-Cu coordination, and could effectively generate NO in situ at a physiological level. Due to the sustained release of heparin and continuous NO generation, the synergistic antithrombogenicity and anti-hyperplasia ability were obtained. The ex-vivo arteriovenous (AV) shunt model for blood perfusion test and metal wire implantation in blood vessels further demonstrated the high biomimetic functionality of potential applications for blood-contacting devices.