| Objective:To experimental synthesis of new medical polyurethane (PU) as a coating substrate with heparin(anti-clotting polymer coating), making the coating metal stents with anticoagulants. In blood compatibility experiment (hemolysis rate and platelet adhesion experiment), it will be tested its anticoagulant effect, and through the animal experiments verify the effectiveness.Materials and methods:1. The coating matrix synthesis:synthesis by chain extension agent (double methyl diethyl b fat (DBM) into two fat the side chain of polyurethane; According to the content of DBM (weight number of copies) different synthesis out PU-3DBM and PU-6DBM; PU-3DBM and PU-6DBM were grafted heparin (HEP), forming new anticlotting has the PU-3DBM-HEP and PU-6DBM-HEP coating.2. Use hemolysis rate and platelet adhesion experiment in the blood compatibility, inspection PU-3DBM-HEP and PU-6DBM-HEP coating anticoagulant effect.3. Dip besmear of the new PU (PU-3DBM, PU-6DBM, PU-3DBM-HEP and PU-6DBM-HEP) coating to metal stent surface, making a anticlotting of stents, implanted experimental animals within living blood vessels; Animal experiments are divided into5groups:PU-3DBM coating group, PU-6DBM coating group, PU-3DBM-HEP coating group, PU-6DBM-HEP coating group and control group (bare metal stents).Results:1. Using Fourier transform infrared spectroscopy (FTIR), chemical analysis the electronic energy (ESCA) and water contact Angle (WCA) to represent the grafted heparin PU; New PU coating materials (PU-3DBM, PU-6DBM, PU-3DBM-HEP and PU-6DBM-HEP) comply with medical polymer requirements.2. In vitro the heparin release test, new PU synthetic grafted of heparin can constantly release heparin in10hours, and is good for blood compatibility.3. Animal experiments show that:(1) PU-3DBM coating group:luminal surface is more smooth than bare stent. The corrosion area more bare metal stents small. Stent was completely blocked. Stents surface almost no cell adhesion objects; Polymer coating thickness of about10micron; The surface of blood vessels has a large stent thrombosis; Vascular endothelial are complete. The lumen is occluded with a fibrin thrombus. Granulomatous inflammation surrounds many struts. Four struts are present in the peri-vascular tissue. Injury is moderate and inflammation is moderate to severe.(2) PU-6DBM coating group:luminal surface is more smooth than bare stent, the corrosion area more bare metal stents small. Hyperplasia thicker, Stents surface almost no cell adhesion objects. Polymer coating thickness of about10micron. Vascular endothelial are very complete. The neointima is thin (up to250microns thick) and mature. Perivascular connective tissue contains a1mm round granuloma. Dilates spaces in the neointima near some struts contains clear particulate debris (possibly polymer). This debris is often surrounded by granulomatous inflammation. Inflammation extends from many strutsinto the tunica media and surrounding adventitial tissues. Injury is moderate and inflammation is severe.(3) PU-3DBM-HEP coating group:luminal surface is more smooth than bare stent, the corrosion area more bare metal stents small. The most hyperplasia thick. Stents surface almost no cell adhesion content, but there are parts of the cock flake coating. Polymer coating thickness of about10micron. Vascular endothelial are very complete. Neointima is up to2.5mm thick and reduces the lumen diameter substantially. Peristrut inflammation is mostly granulomatous. Injury is mild and inflammation is moderate.(4) PU-6DBM-HEP coating group:luminal surface is more smooth than bare stent, the corrosion area more bare metal stents small. The most hyperplasia thick. Stents surface almost no cell adhesion objects. Polymer coating thickness of about10micron. Vascular endothelial are very complete. The neointima is up to1.2mm thick. Fibrin is in the neointima near most struts. Dilates spaces in the neointima near some struts contains clear particulate debris (possibly polymer). This debris is often surrounded by granulomatous inflammation. Inflammation extends from many struts into the tunica media and surrounding adventitial tissues. Injury is mild and inflammation is moderate.(5) the control group:stents visible scratches the surface, holes, bubble and impurities, the surface has blood coagulation and the growth of blood vessels; Bare metal stents endothelial proliferation the minimum; There was an obvious surface adhesion material; Vascular endothelial are very complete. A thin mature neointima is up to250microns thick. Injury and inflammation are mild. Mature neointima is up to300microns thick. Low numbers of macrophages are near some struts. Small amounts of fibrin are in the neointima near most struts. Injury is absent and inflammation is mild.Conclusion:These experiments on the surface modification of metallic stent made a bold attempt to overcome the always stents surface instability and carry drugs matrix uncertainty characteristics. The new synthesis methods of polyurethane, technology conditions, such as bottom material choose the correct. Test method and data for the future research continue to provide the foundation. Polyurethane grafted heparin anticoagulant, fight together after effect is ideal, the long-term stability and medicinal properties to maintain good. The new matrix and metal stents adhesion of the firm by the test confirmed, coating of the metallic stent improve the corrosion resistance, reduce metallic corrosion, titanium (Ti), nickel (Ni) into the blood. New coating has good anticoagulant effect. PU-6DBM has better stability and the surface of anticoagulant effect than PU-3DBM. And volume loss of PU grafting heparin is not obvious. New coating cause fibrin hyperplasia. The new matrix synthesis environment, biological characteristics and biocompatibility needs to be improved and enhanced, and puts forward the test items and standards needs to be strengthened.
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