Study On Selective Endothelialization By Functionalizing Ti-O Surface With Chiral Selenocystine And Peptide KREDVC

In recent years,drug-eluting stents?DES?have become the main treatment for atherosclerosis,but late stent thrombosis and restenosis causing by incomplete endothelialization are still the main reasons for implantation failure.Therefore,Endothelialization or inducing endothelialization in situ is a promising strategy to prevent late thrombosis.So,in situ endothelialization for drug-eluting stents by immobilizing biological functional molecule has been a hot topic.In this paper,a polydopamine transition layer was deposited on the surface of Ti-O film,and then chiral selenocystine and peptide KREDVC were immobilized on the surface of Ti-O film to achieve a functional chiral surface with NO release,for the selective endothelialization in an inflammatory environment.In this paper,X-ray photoelectron spectroscopy?XPS?,atomic force microscopy?AFM?,water contact angle?WCA?,amino or carboxyl quantification,QCM-D and sample catalytic release of nitric oxide?NO?were used to characteriz the modified materials.The results of XPS,AFM,WCA,amino or carboxyl quantification and QCM-D indicated that chiral selenocystine and peptide KREDVC were successfully immobilized on the polydopamine layer,and the grafted mole ratio of L-or D-selenocystine and the KREDVC peptide was⁷:1.Although QCM-D results showed almost no difference in the grafting amount between L-type surface and D-type surface,the L-type surface had more protein adhesion than the D-type surface.The results of NO release indicated that samples can stably and continuously release NO,and NO generation catalyzed by sample L-REDV was1.21±0.05×10^-10mol·cm^-2·min^-1,whereas that of sample D-REDV was0.75±0.06×10^-10mol·cm^-2·min^-1.The results of platelet adhesion and activation,endothelial cells?ECs?static culture,smooth muscle cells?SMCs?static culture,EC and SMC co-culture,macrophages?MA?static culture,and ECs culture in H₂O₂/EC injury model indicated that the functional chiral coating with NO release can inhibit platelets adhesion and activation,inhibit SMCs adhesion and proliferation,promote ECs selective adhesion through the synergistic action of chiral,NO and peptide KREDVC,and showed a good anti-inflammatory and antioxidant properties.The results of mouse abdominal aortic implantation showed that the neointimal thickness of L-REDV was 62±4?m and the endothelialization rate was 87%.While the neointimal thickness of Ti was 98±17?m and the endothelialization rate was 8%indicating that the functional chiral coating with NO release could inhibit neointimal hyperplasia and promote the complete endothelialization.In summary,this paper obtained a functional chiral surface with NO release by immobilizing a non-specific chiral selenocystine molecule catalytic release NO and an extracellular matrix polypeptide KREDVC,which could enhance the biocompatibility and promote the selective endothelialization.