Experimental Study Of Elastin-like Polypeptides As A Thermosensitive Liquid Embolic Agent For Treatment Of Gastroesophageal Varices

Objective Elastin-like polypeptides(ELP) is a new type of thermosensitive liquid embolic agent, we intend to use it to treat gastroesophageal varices. Its feasibility, safety and efficacy will be evaluated, and it will be provided as a new safe, effective, economical liquid embolic material for the clinical endoscopic treatment of esophageal varices. Methods(1) ELP will be synthesized and optimized by genetic engineering methods: Gelation time and viscoelastic of three kinds of ELP will be tested, and one of them will be selected which should have a good viscoelastic can against blood flow erosion and can aggregation rapidly. Viscosity of three different concentrations ELP will be detected, and one that can be injected within endoscopic at room temperature will be chosen for further experiments.(2) Evaluation of embolic effect in vitro: Construction the simulation embolic model device, ELP injected through microcatheter, explore the feasibility and effective of ELP and confirmed its operability under 37℃. Glass containers with glass beads will be cultured under 37℃after the end of the experiment, one week after re-check the continuity and dispersion conditions.(3) Preliminary evaluate the embolic effect of ELP in vivo: Methylene blue-ELP will be injected in femoral artery, explore the possibility and stability after embolism; assess the biocompatibility by monitoring the rabbit blood routine examination, liver function and kidney function indicators; assess embolic effect and stability of ELP in vivo by pathological examination and whether there is ectopic embolism. Results(1)ELP120-Tyr7 has a shorter gel time and better viscoelastic for embolization. After comparing the viscosity, we found 750 umol is the most suitable concentration for embolicing vascular, and can be injected under endoscop.(2)The vitro experiments confirmed that ELP can embolic the simulation embolic model. Cutting the micro-catheter we found the wall were smooth after the experiment, and no stick tube. ELP evenly and stably distributed above the glass beads after agglutination and no precipitation flow. After 1 week, the glass container was not re-pass, ELP gel has good stability.(3)ELP successfully embolized the femoral artery, and did not occur the symptoms of ectopic embolism. Blood routine examination, liver function and kidney function were no significant difference between pre-embolization and after the embolization(P>0.05). Pathology results showed that ELP can stability exists in the vascular, and there were no vessel wall damage and abnormal morphological changes. Conclusions(1) ELP120-Tyr7 and the concentration is 750 umol of the ELP displayed a satisfactory embolic effect. ELP as a liquid embolic agent is the best choice for endoscopic treatment of gastroesophageal varices.(2) The simulation embolic model device can simulate the vivo environment effectively, and test the feasibility of the embolic agent. After embolization, ELP was stable, has good performance in embolization, and no difficult of injection and stick tubes. It was operatibility under 37℃.(3) ELP are a thermosensitive gel that have good biocompatibility, can be achieved blood clots and no tissue damage. It can be stably present in the vessels and no ectopic embolism after embolization.