| The percutaneous transluminal angioplasty (PTCA) as the main interventional therapies of stenosis and occlusion of blood vessel has induced restenosis (30%-50%), which influence it's late curative effect. The introduction of stents in the clinical practice was a major breakthrough in the field of percutaneous coronary intervention. Its success assistant with the anticoagulant and antiplatelet therapies is thought to be due to its ability to reduce the acute elastic recoil and long-term negative remodelling associated with PTCA. The stents may also induce a more chronic and pronounced vascular response than angioplasty alone which has been defined as in-stent restenosis (ISR). There are still relatively high in-stent restenosis rates (15%-25%) after stenting, caused by the excess neointimal hyperplasia because of the smooth muscle cell migration and proliferation. Although many anti-proliferation drugs have good effects in animal experiments the clinical uses of them have depressed us. An important reason is that they could not reach the sufficient concentration at local vascular vessel by systemic therapy. Drug-eluting stents (DES) are coated with a bioresorbable polymer capable of releasing single or multiple bioactive agents into the bloodstream and surrounding tissues. Local deliveries to the vasculature achieves high regional drug concentrations and decrease the ISR to below 10%, with prolonged retention at lower doses and reduces systemic toxicity.The issues in the preparation process of DES are generally focused on three chief aspects, including coating material and its preparation methods, the selection of biological agents, the control release of drugs. In this article the biological agent is domestic-made platelet glycoproteinⅢa receptor monoclonal antibody (mAb) and the coating material is L-polylactic acid (PLLA). The spray method based on ultrasonic atomization is used to prepare PLLA coated stents, which is immersed into the mAb solution passively absorbed by coating. After evaluating the qualities of polymer coating and mAb eluting stents, we have examined the biosecurity and validity of prevention and cure ISR by implanted exceeding mAb eluting stents into rabbit iliac arteries. The major contents and results of the research are as follows.①The spray equipment for experiment was designed and produced according to the character of spray process and the principle of ultrasonic atomization. The equipment were composed of four parties, including atomization module, gas-carrier module, solution-container module, and stent-carrier module. The atomization module could atomize the polymer solution through a drop-in ultrasonic atomizer located in the cylindrical water container. The gas-carrier module could control and adjust the outflow flux of N2 in the high-pressure air tank through gas flowmeter. The polymer-solution container and nozzle were made of glass because they were easy to atomize polymer solution and clear. The stent-carrier module helped to prepare uniform polymer coating by the means of making the stent move back-and-forth in front of nozzle at the time of maintaining circumrotation. This equipment could prepare the ideal polymer coating on the stent surface and easy to spary multi-coating.②The technics process was introduced in this text. The optimal parameters, which were determined by counting the un-uniform district, were spray time 30s, PLLA concentration 1.0 mg/ml, rotate speed 50 rpm.③The distribution and morphologies of PLLA coatings on the stent surface prepared under the optimal parameters were visualized through fluorescence staining and scanning electron microscopy (SEM), combined with computer image analysis method to estimate the uniformity, hole distribution and surface roughness of coating. In addition the morphologies of PLLA coating were examined both pre- and post-expansion in vitro. The results suggest the PLLA coating has favourable hole distribution and surface morphology, and no cracks, break-off, or turnup both pre- and post-expansion.④The presence of the PLLA coating over the entire surface of the stent was evidenced by means of a fluorescence staining method. Whether if the PLLA combine with the mAb or not was confirmed by the DSC. After these two experiments we could make certain the feasibility of passive absorption of mAb in the PLLA coating on the stent surface. The convergence degree of fluorescence intensity distribution indicated the uniformity of PLLA coating pore distribution, which was closely related to the distribution of mAb in PLLA coating. The results indicated there are no chemistry reaction between the PLLA and mAb, and PLLA has no influence on the biology activity of mAb.Stents eluting the mAb were tested for their adsorption characteristics by radioisotope technique with 125I labelled mAb. The elution rates were then measured in looped circuits at different velocities and durations. The amount of mAb adsorbed onto the PLLA coating was dependent on the concentration and duration of immersion in the solution. We have tested three different concentrations for 120h. Maximal mAb binding was therefore defined as the amount of agent bound to stent wires after 72 hours immersion in a 2 mg/ml solution. The method of preparation the mAb eluting stent and flow velocity significantly influenced the elution characteristics for a continuous perfusion of more than 2 weeks.⑤We implant the mAb eluting stents and 316L stainless steel stents the control in rabbit iliac arteries to study the bio-security validity of prevention and cure ISR by sliding microtome, SEM, transmission electron microscope (TEM), immunohistochemi- stry, tissue stain and biochemistry methods. The blood vessel and serum samples were got from the rabbits after stents implantation for 1week, 4weeks and 12weeks. The results suggests the mAb eluting stents are biocompatible and can inhibit the thrombosis and neointimal hyperplasia by accelerating the endothelialization of the stent surface and inhibit the smooth muscle cell migration and proliferation.
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