In-stent restenosis and subsequent thrombosis remain a significant complication following the implantation of coronary stents. Different approaches have been used in developing novel coronary stents to protect against thrombosis and minimize restenosis. In the present study, we designed a biomacromolecular layer-by-layer coating with heparin, vascular endothelial growth factor (VEGF), and fibronectin onto nickel-free titanium surface to improve blood compatibility and endothelial cell proliferation. The multilayer assembling process was monitored by water contact angle and surface plasmon resonance, respectively. With increasing the number of layers, the deposition of polyelectrolyte as self-assembled ultrathin multilayer films showed linear growth of absorbance. In vitro blood compatibility results revealed that the fabricated layers prolonged activated partial thrombin time and prothrombin time, reduced platelets activation and aggregation, and reduced blood hemolysis rate. Cell adhesion and growth results showed that the assembled multilayer films significantly promoted cell attachment and growth, and the endothelialization property of the multilayer films was preferable compared with the untreated titanium disk. In conclusion, these results suggest that titanium surface modification using biofunctional multilayer films composed of heparin, VEGF, and fibronectin may serve as a potential approach to inhibit thrombosis and promote re-endothelialization of cardiovascular stents.
An eluting-stent system with mAb dispersed in the PLLA (poly (L-lactic acid)) was validated in vitro. Specifically designed spray equipment based on the principle of ultrasonic atomization was used to produce a thin continuous PLLA (poly (L-lactic acid)) polymer coating incorporating monoclonal antibody (mAb). This PLLA coating was observed in light microscopy (LM) and scanning electron microscopy (SEM). The concentration of the monoclonal antibody (mAb) to the platelet glycoprotein (GP) IIIa receptor and the eluting rate were then measured by a radioisotope technique with (125)I-labelled GP IIIa mAb. An in vitro perfusion circuit was designed to evaluate the release rates at different velocities (10 or 20 ml min(-1)). The PLLA coating was thin and transparent, uniformly distributed on the surface of the stent. Three factors influenced its thickness: PLLA concentration, duration and gas pressure. The concentration of mAb was influenced by the duration of absorption and the concentration of the mAb solution; the maximum was 1662.23 + or - 38.83 ng. The eluting rate was fast for the first 2 h, then decreased slowly and attained 80% after 2 weeks. This ultrasonic atomization spray equipment and technological process to prepare protein eluting-stents were proved to be effective and reliable.
Diabetes has been recognized as a major risk factor to cause macrovascular diseases and plays a key role in aortic wall remodeling. However, the effects of diabetes on elastic properties of aortas remain largely unknown and quantitative mechanical data are lacking. Thirty adult rabbits (1.6-2.2 kg) were collected and the type 1 diabetic rabbit model was induced by injection of alloxan. A total of 15 control and 15 diabetic rabbit (abdominal) aortas were harvested. Uniaxial and biaxial tensile tests were performed to measure ultimate tensile strength and to characterize biaxial mechanical behaviors of the aortas. A material model was fitted to the biaxial experimental data to obtain constitutive parameters. Histological and mass fraction analyses were performed to investigate the underlying microstructure and dry weight percentages of elastin and collagen in the control and the diabetic aortas. No statistically significant difference was found in ultimate tensile strength between the control and the diabetic aortas. Regarding biaxial mechanical responses, the diabetic aortas exhibited significantly lower extensibility and significantly higher tissue stiffness than the control aortas. Notably, tissue stiffening occurred in both circumferential and axial directions for the diabetic aortas; however, mechanical anisotropy does not change significantly. The material model was able to fit biaxial experimental data very well. Histology showed that a number of isolated foam cells were embedded in the diabetic aortas and hyperplasia of collagen was identified. The dry weight percentages of collagen within the diabetic aortas increased significantly as compared to the control aortas, whereas no significant change was found for that of elastin. Our data suggest that the diabetes impairs elastic properties and alters microstructure of the aortas and consequently, these changes may further contribute to complex aortic wall remodeling.
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