Establishing Endothelial Progenitor Cells Specific Capture Surfaces And Evaluating Performance Of These Surfaces

Endothelial progenitor cells (EPCs) originating from bone marrow play a significant role in re-endothelialization of damaged blood vessels after stenting. The application of EPC capture stents showes a better therapeutic approach to rapidly create an in vivo endothelialization of stent surfaces than drug eluting stents and bare metal stents. However, some problems are still not be solved:1) thrombosis maybe pose the risk of failure of cardiovascular device, due to no anticoagulant modification on the surface;2) under high shearing force in the vessel lumen, rarely amounts of EPCs could adhere onto the stents, and then lead to obstacle of rapid endothelialization;3) stents made with nondegradable material prevent the vasoconstriction and vasodilatation associated with late thrombosis, late restenosis and chronic inflammation, late favorable remodeling and vessel reactivity at the site of stent placement.Recent studies suggest that infusion of EPCs can promote postnatal neovascularization of ischemic tissue after myocardial infarction, but it is so hard for EPC to land onto the injure site for angiogenesis that the methodology of how to transport EPC to the local site is very meaningful.This paper focuses on the following researchs based on the above problems. First, this study deals with improving the hemocompatibility and enhancing EPC colonization on titanium substrate modified by covalently bonding PEG600or PEG4000, then end-grafting of an anti-CD34antibody. Second, superparamagnetic nanoparticles (MNPs), which could specific bind to EPCs were prepared and used to locally deliver EPCs to stent surfaces to accomplish reendothelization and to lesion distribution of myocardial infarction to form blood vessels by using magnetic gradient-related mechanisms. At last, we examined in vitro the possibility of targeting of EPCs binding with MNPs to the surfaces of iron stents to accomplish rapid-reendothelization in the presence of magnetic fields by using paired permanent magnets. The contents of the paper are listed as follow:1. A chemically hydroxylated titanium surface was aminosilanized and further covalently graft with PEG. The influence of reaction conditions on the grafted quantity was studied. The blood-compatibility of the PEGylated surface with different chain density and chain length was evaluated and the results show that the PEGylated surfaces with higher grafted density and longer chain length show less fibrinogen adsorption, less fibrinogen y-chain expose, less adherent platelets and lower activation of the adherent platelets. In addition to the influence on blood, the longer chain PEGylated surfaces could resist not only SMC attachment and proliferation but also macrophage attachment and death.2. A chemically hydroxylated titanium surface was aminosilanized, which was further used for covalent grafting of poly (ethylene glycol) and the antibody. The grafting efficiency was verified in each step. In vitro platelet adhesion analysis confirmed superior hemocompatibility of the modified surface over the control. Affinity of EPC to the surface and inhibition of smooth muscle cell adhesion, two prerequisites for endothelialization, are demonstrated in in vitro cell culture. While the coating selectively stimulates EPC adhesion, its antifouling properties prevent formation of an extracellular matrix and proliferation of the cells. Potent inhibitory effect on macrophage activation and the relative stability of the coating render this technique applicable.3. Anti-CD34has been covalently grafted to PEG coated MNPs, which were synthesized following a simple two-step coprecipitation approach. Such anti-CD34coated MNPs have good magnetic properties and target effect to EPCs. In vitro and in vivo cells trapping results show that MNP could multiple promote EPCs attachment and inhibit SMCs attachment in the presence of magnetic fields. Such MNP have good blood-compatibility.4. Owing to corrosion, it is hard to modify the surface of iron to accelerate endothelialization. Under anti-CD34coated magnetic nanoparticles assisting, stimulated endothelialization of iron could be accomplished.