Nitric Oxide Generating Coating With Chirality For Surface Modification Of Cardiovarscular Stents

Cardiovascular stents are one of the effective methods to treat coronary atherosclerosis.However,the clinical application of stents is still hampered by the complications such as late stent thrombosis and in stent restenosis.A large number of studies have shown that the topography,charge,roughness,chemical composition,functional groups and the wettability of the stent surface significantly influence its biocompatibility,since a variety of physical and chemical strategies have been developed for surface modification of cardiovascular stents.But how surface chirality affect the hemocompatibility and cytocompatibility is still far less known.In this research,the influence of surface immobilized chiral lysine and tartaric acid on hemocompatibility and cytocompatibility was carefully investigated,and then NO and copper ion were incorporated on the surface to show synergy effect with molecular chirality to promote endothelialization,inhibit platelet activation and suppress smooth muscle cell proliferation.Polydopamine coating was used to immobilize chiral lysine directly,and tartaric acid was grafted via a 1,6-hexanediamine linker.Then the physical and chemical properties and biocompatibility of the chiral molecular immobilized surface were studied.Material characterizations showed that the L-lysine(or tartaric acid)immobilized surface had same grafting amount with D-lysine(or tartaric acid)immobilized surface,and the surface wettability,chemical composition,roughness,and topography had no significant difference between the L-and D-surface.However,the L-lysine immobilized surface had greater bovine serum albumin and fibrinogen adsorption,also the activation of fibrinogen was more than D-lysine immobilized surface.The D-tartaric acid immobilized surface with more bovine serum albumin and fibrinogen adsorption but less fibrinogen activation.As a result,the L-lysine immobilized surface had greater platelet adhesion and activation than the D-lysine immobilized surface,and the L-tartaric acid grafted surface showed less platelet adhesion but more serious activation than the D-tartaric acid grafted surface.The surface with L-Lysine grafting had greater promoting effect on the growth of endothelial cells and smooth muscle cells than the D-lysine immobilized one.These results inspired us to construct an L-amino acid immobilized surface to promote endothelialization.But how to selectively inhibit platelet activation and smooth muscle cell proliferation? NO generation seemed to meet these requirements as reported in the past.Hence,the L-selenocystine was chosen as catalyst to be immobilized on the surface for NO catalytic releasing.Compared with the unmodified and the D-selenocystine grafted surface,the immobilization of L-selenocystine had greater NO generation in the presence of donor to inhibit platelet adhesion and activation and suppress smooth muscle cell proliferation,and the NO showed synergy effect with L-type of selenocystine to promote endothelialization.However,the inevitable protein adsorption and cell covering will reduce NO releasing thereby weakening the biofunction of the materials.So,the nanoscale copper-based metal organic frameworks were immobilized by using polydopamine as coating matrix for NO catalytic generation and copper ion delivery to enhance the property of anticoagulation,anti-hyperplasia and endothelial promoting.The in vitro and in vivo studies indicated that the nanoscale copper-based metal organic frameworks immobilized surface had adaptable NO release and copper delivery,and could selectively promote endothelialization but inhibit thrombosis and neointimal hyperplasia,as well as regulate the inflammatory response.Furthermore,the L-lysine was immobilized onto the coating.This coating maintained good ability to inhibit platelet activation,and the NO generation,copper ion delivery and Ltype of chirality play a synergistic action in enhancing endothelial proliferation in the later experiments.However,the NO generation rate was significantly reduced by the immobilization of chiral lysine and then weakened its inhibitory effect on smooth muscle cell proliferation.Hance the method to constract a chiral NO generating surface should be reconsidered in the futher investigation.In summary,the influence of surface chirality on hemocompatibility and cytocompatibility was investigated in this work.Take advantage of the cell promoting effect of L-type amino acid immobilized surface,we developed a multifunctional coating to promote endothelialization,suppress thrombosis and inhibit intimal hyperplasia selectively by incorporating NO generation,copper ion delivery and chirality for surface modification of cardiovascular stents.This study not only provides an important guidance for designing a biocompatible surface,but also proposes a new concept in surface modification of cardiovascular stents.