Immobilization Of Heparin-SDF-1?/PLL Nanoparticles On Materials And Biocompatibility Investigation

Thee percutaneous coronary intervention has become one of the most common therapies of cardiovascular diseases due to its high efficiency and low damage.However,the thrombosis and restenosis are easy to form because of the hurt vascular endothelial cells during the stent implantation.So it is necessary to achieve rapid re-endothelialization on stent surface.In this work,the stainless steel(SS)surface was modified by constructing dopamine(DM)coatings and subsequently immobilizing heparin-PLL nanoparticles with stromal-derived factor-la(SDF-1?),to obtain a better compatibility micro-environmentwith anticoagulation,antiproliferative and induced-endothelialiation properties.The structure of SDF-la has specific binding site,heparin will directionally link to SDF-la through electrostatic bonding.On the other hand,heparin can interact with PLL electrostatically and formulate nanoparticles with three-dimensional structure.Under weakly alkaline conditions,dopamine(DM)can adheres to the stainless steel surface firmly via autopolymerization and formulate a variety of functional groups such as quinonyl,amino,phenolic hydroxyl on material surfaces.Then the DM coatings can interact with amino group of PLL by Schiff base reaction or Michael addition reaction to immobilize the Hep-SDF-1?/PLL nanoparticles.The size and Zeta potential were detected by using the Laser Particle Size Analyzer to determine the stability and uniformity,the introduction of SDF-la result in the reduction of nanoparticle size.The FTIR and XPS results showed that the nanoparticles were successfully immobilized on the DM coatings.The AFM and SEM test directly showed the morphology of Hep-SDF-1?/PLL nanoparticles,and the particle had uniform distribution and no agglomeration.The water contact angle test showed the improved hydrophilic properties of the samples.The exposed heparin and SDF-la amount on the DM coatings were investigated by toluidine blue test and immunohistochemistry,respectively,indicating that the modified samples had high heparin density and SDF-la density.Heparin release result showed that the nanoparticle structure would regulate the release of heparin to achieve long term controlled release,and the more of loaded SDF-la in nanoparticles,the less of release amount.SDF-la release result indicated that the SDF-la would release at least 21 days.NPS50 had the least release content and the others tended to have similar release trend.Blood compatibility evaluation in vitro results suggested that the samples modified with Hep-SDF-la/PLL nanoparticles had better properties than SS and DM with less platelet adhesion and aggregation,higher AT III binding activity,prolonged activated partial thromboplastin time(APTT)and lowerFibrinogen adhesion and degeneration.Vascular cell compatibility evaluation in vitro results investigated that the Hep-SDF-la/PLL nanoparticle micro-environment would promote the attachment and proliferation abilities of endothelial cells(ECs)and endothelial progenitor cells(EPCs),and SDF-la could induce the formation of hollow tube-like structures by endothelial cells.Because of the release heparin,the Hep-SDF-la/PLL nanoparticles inhibited SMCs proliferation compared with SS and DM,significantly.Induced-endothelialiation evaluation in vitro showed that the Hep-SDF-la/PLL nanoparticle micro-environment would wonderfully promote EPCs chemotaxis and ECs migration.The mechanism study indicated that the biocompatibility of the modified samples were controlled both by heparin and SDF-la.Heparin played important roles in bloodcompatibility and the early cell activity(1D),while the SDF-la affected the later viability of the cells.In conclusion,the Hep-SDF-la/PLL nanoparticles micro-environment provided an important reference for achieving anticoagulant,antiproliferative and induced-endothelial biofunction of cardiovascular materials.