Multifunctional nanocoatings with synergistic controlled release of zinc ions and cytokines for precise modulation of vascular intimal reconstruction.

Vascular stent implantation remains the major therapeutic method for cardiovascular diseases currently. We here introduced crucial biological functional biological function factors (SDF-1α, VEGF) and vital metal ions (Zn2+) into the stent surface to explore their synergistic effect in the microenvironment. The combination of the different factors is known to effectively regulate cellular inflammatory response and selectively regulate cell biological behavior. Meanwhile, in the implemented method, VEGF and Zn2+ were loaded into heparin and poly-l-lysine (Hep-PLL) nanoparticles, ensuring a controlled release of functional molecules with a multi-factor synergistic effect and excellent biological functions in vitro and in vivo. Notably, after 150 days of implantation of the modified stent in rabbits, a thin and smooth new intima was obtained. This study offers a new idea for constructing a modified surface microenvironment and promoting tissue repair.

Improving hemocompatibility and accelerating endothelialization of vascular stents by a copper-titanium film.

Bio-inorganic films and drug-eluting coatings are usually used to improve the hemocompatibility and inhibit restenosis of vascular stent; however, above bio-performances couldn't combine together with single materials. In the present study, we reported a simple approach to fabricate a metal film with the aim of imparting the stent with good blood compatibility and accelerating endothelialization. The films with various ratios of Cu and Ti were prepared through the physical vapor deposition. Phase structure and element composition were investigated by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. The releasing volume of copper ion in Cu/Ti film was determined by immersing test. The hemolysis ratio, platelet adhesion and clotting time were applied to evaluate the hemocompatibility. The proliferative behaviors of endothelial cells and smooth muscle cells under certain copper concentration were investigated in vitro and in vivo. Results indicated that copper-titanium films exhibited good hemocompatibility in vitro; however, the increase of Cu/Ti ratio could lead to increasing hemolysis ratio. Endothelial cells displayed more proliferative than smooth muscle cells when the copper concentration was <7.5µg/ml, however both cells tended to apoptosis to some degree when the copper concentration was increased. The complete endothelialization of the film with low copper in vivo was observed at the 2nd week, indicating that the copper-titanium film with the lower copper concentration could promote endothelialization. Therefore, the inorganic copper-titanium film could be potential biomaterials to improve blood compatibility and accelerating endothelialization of vascular stents.

Mechanical behavior and blood compatibility of copper-containing films as potential biomaterials.

Surface modification is one approach to enhance the biocompatibility of implanted cardiovascular devices. In this work, a copper-containing film used to blood contacted biomaterials was prepared by vacuum arc deposition. The phase composition of the films was investigated via X-ray diffraction, and the adherence strength of the films was evaluated with conventional deformation tests. Blood compatibility of the films was characterized by hemolysis ratio, clotting time and platelet adhesion etc. The surface of inferior vena cava filters were smooth and uniform, no cracks or delaminations were observed on the deformed surface. These results indicate that the mechanical behavior of the films is suitable for withstanding deformation stresses as operation in clinic. Good blood compatibility of the copper-containing films was identified through experiment in vitro, the activated partial thromboplastin times (APTTs) of Cu/Ti films were similar to that of the uncoated substrate, and Cu/Ti films were also found to inhibit platelet adhesion comparing to the nitinol substrate. However, with increasing ratio of Cu/Ti, the hemolysis ratio increased, resulting in platelet damage. These results indicate that the copper-containing film has potential application on blood contacted devices.

Improved anticoagulation of titanium by sequential immobilization of oligo(ethylene glycol) and 2-methacryloyloxyethyl phosphorylcholine.

Titanium and its alloys have been widely used for blood-contacting biomedical devices; however, their blood compatibility needs to be improved. In this study, titanium surface was modified by sequential immobilization of oligo(ethylene glycol) (OEG) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to improve its anticoagulation. Water contact angle results showed an excellent hydrophilic surface after the immobilization. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed that OEG and MPC were successfully immobilized on titanium surface. Static platelet adhesion and APTT (activated partial thromboplastin time) experiments suggested that the anticoagulation of titanium was significantly enhanced by the immobilization of OEG and further by subsequent MPC grafting. The approach in the present study opens up a window of promising an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.