Immobilization Of Heparin/Poly-L-Lysinenanoparticles On Titanium Surface To Improve The Blood Compatibility

Cardiovascular diseases are one of the most important diseases that endanger human health. In clinical, implantable devices such as artificial blood vessels, artificial heart valves and cardiovascular stents have been widely used in the treatment of cardiovascular diseases. However, blood compatibility of biomaterials continually being a serious problem. Focused on these shortcomings, aimed to improve the blood compatibility of biomedical materials, this work modified the titanium surface by constructing dopamine (DM) coatings and subsequently immobilizing heparin-PLL nanoparticles on the DM coated surface.Under weakly alkaline conditions, dopamine can firmly adheres to the titanium surface via autopolymerization and formulate variety of functional groups (phenolic hydroxyl, quinonyl, amino) on material surfaces. By use of these characteristics, DM coatings can be deposited on titanium surface. On the other hand, negative charged heparin can electrostatically interact with PLL and formulate nanoparticles with three-dimensional structure. DM coated surface can interact with amino group by Michael addition or Schiff base reaction, which allows covalently binding the amnio-rich Hep/PLL nanoparticle. The size and Zeta potential value of nanoparticles with different process are detected by Zeta potential analyzer. The toluidine blue method is used to detect the heparin content in different nanoparticles. The FTIR and XPS results showed that Hep/PLL nanoparticles are successfully immobilized on the DM coated surface. The morphology and hydrophobic properties of the nanoparticle immobilized surface are characterized with AFM and water contact angle test. Furthermore, amino group density, heparin amount and nanoparticle amount on the DM coated surface are quantitatively characterized by acid orange II test, toluidine blue test and electronic microbalance, respectively.Platelet adhesion and activation experiments indicate that the immobilization of nanoparticles significantly inhibits the adhesion of the surface of Platelets. The results of fibrinogen degeneration test showed that the degeneration of fibrinogen on the nanoparticles immobilized surfaces has been significantly decreased, and thereby efficiently inhibit the platelet aggregation and activation. Clotting time test indicates that, both APTT and TT are significantly prolonged after nanoparticles immobilization. However, the PT is not sensitive to heparin. As a result, the test results exhibit no change. The heparin dynamic release and platelet adhesion experiments show that the heparin exhibit burst release in infancy, which may contribute to preventing acute coagulation, and then the release rate changed slowly, which allows continuous and effective anticoagulant for a long time.According to the results of mechanism research, the formation of Hep/PLL nanoparticle is affected by many external factors such as ion concentration of disperse system, pH value, molecular weight of PLL. The results also indicate that under the weakly alkaline PBS condition, nanoparticle exhibit good performance in stability, uniformity and anticoagulant effect.