Research On A Novel Stent Coated With Antibody Against CD34 Capturing Endothelial Progenitor Cell Carried By The Degradable Polymer

In-stent restenosis(ISR) is the major drawback of percutaneous coronary interventions which is increasingly attracting interests of medical science. Research of drug eluting stents (DES) is very popular because DES are successful in a large majority of patients in preventing restenosis. The currently available drug-eluting stents have been thought to increase the risk of thrombosis by delayed endothelialization as endothelial progenitor cell proliferation is also inhibited. As the defect mentioned above, a novel stent is being expoldered to prevent thrombosis , to inhibit neointimal hyperplasia when bare stent is exposed to blood circulation ,and to reduce the incidence of in-stent restenosis by accelerating endothelialization.The research firstly synthesized a new degradable tri-block copolymers PEG-PLA-PGL which has active groups, and then treated the surface of the metal stent by chemistry technology , connected the stent and the antibody against CD34 . The anti-CD34 antibody was bounded with the polymer by N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) conjugation technology so as to establish anti-CD34 antibody eluting stent. And we evaluated the feasibility, safety and effectiveness of the stent in preventing restenosis in animal experiments.The investigation indicated: 1,ratio of 17:23:63 among PEG,PLA and PGL, molecular weight of 18.0 and 14.6(×103) Da, had stable degradable property , and satisfied the time of complete endothelialization . The results showed that in flowing solution ,the changes of weight and molecular weight were more slowly compared with static degradation .That attributes to the micro-circumstance on polymer surface.2,We connected the stent and the antibody against CD34 by treating the surface of the metal and introducing coupling agent. We initially detected the static state contact angle to estimate the bonding force between coating and stent , and to evaluate the effects of both acid density and treating persistence time towards polymer spreading on stent surface. We discovered that when the acid density sustained in the level of 0.20mmol/L,the contact angle almost achieved to the minimal level, that is to say that the surface energy of stent and bonding force is both strongest at that time. We also discovered that when the treating persistence time maintained at the level of 0.5 to 6 hours, the contact angle would increasingly small, and on the other hand, it seemed to raise when the treating time beyond 6 hours. That attributed to the surface roughness and so on. 3,We successfully connected the antibody against CD34 and the biodegradable polymer of PEG–PLA–PGL by N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) conjugation technology. 4,The way that anti-CD34 antibody was bounded to the polymer by N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) conjugation technology was very successful and better than mechanical adherence. 5,Endothelial progenitor cell grew in a stable way in stents coated with CD34 antibody carried by tri-block copolymers PEG-PLA-PGL. And endothelial progenitor cell matured towards endothelial cell and established active layers of endothelial cell at last . The experiment indicated that the CD34 antibody eluting stent could capture endothelial progenitor cell effectively and accelerate endothelialization. 6,PEG-PLA-PGL has fine biocompatibility, which is feasible and safe for clinical application as carrier of drug eluting stents.7,The stent coated with antibody against CD34 carried by the degradable polymer maybe useful for reducing in-stent restenosis by accelerating endothelialization compared with the bare metal stent.The results of this experiment could lead to profound investigation of polymers as coatings of novel stents. Our research provides new theory and experiment evidence for further exploring novel polymer coating of metal stent .Through small animals experiments, The next step we will do is to evaluate the long term effects of stent coated with CD34 antibody carried by biodegradable polymer to ISR of he lesions of coronary arteries .