The Development And Experimental Study Of A New Type Of Filling Stent-graft For Ascending Aortic Aneurysm

BackgroundThe ascending aorta aneurysm refers to the abnormal expansion of the wall of the ascending aorta to more than 1.5 times of the normal diameter,and can lead to sudden death by rupture of aorta.The ascending aorta is the most common area involved by aneurysmal dilation.It is estimated that the ascending aortic aneurysm accounts for about 45% of all thoracic aortic aneurysms.At present,the main therapeutic method for ascending aortic aneurysm is replacement of ascending aorta under extracorporeal circulation,which requires thoracotomy and cardiopulmonary bypass,with larger trauma and higher operative risk.Furthermore,such diseases are prevalent in the elderly.Many patients cannot tolerate open surgery because of advanced age and multiple comorbidities.If treated with conservative treatment alone,the mortality will be as high as 58%.The minimally invasive treatment of ascending aortic aneurysm is urgent to be solved.Endovascular technology,for its less invasive nature,low complication rate and mortality,has been widely used as minimally invasive treatment for lesions in abdominal aorta,descending thoracic aorta,and aortic arch.Nowadays,the endovascular technology has been explored to be used in the treatment of ascending aortic aneurysm.However,the available tube graft needs more than 15 mm of normal aortic wall as the landing zone to achieve stable anchoring,while the ascending aorta is relatively short,with coronary artery at the proximal end and the supra arch branches at the distal end.It is often difficult to provide enough landing zone.Further,with the continuous impact of the pulsating blood flow in the ascending aorta,the graft is prone to complications such as migration and endoleak,leading to higher requirement for landing zone.Therefore,the traditional graft system and related technical methods used in the thoracic descending aorta are not suitable for the morphological and hemodynamic characteristics of ascending aortic aneurysm.Thus,a new design of filling stent graft is proposed in this project: A covered stent surrounded by a fillable endobag,which can be filled with an in situ curing polymer.Once the polymer-containing endobags fill the aneurysm sac,the stent graft can be anchored within the aneurysm sac to achieve positional stability.At the same time,the filled endobag eliminate the aneurysm sac and consequently eliminate the potential space for blood flow in the aneurysm,consequently decreasing the risk of endoleak.Therefore,based on the above concept of stent graft design,we will develop a new filling stent graft system,verify its feasibility via in vitro experiments,and then evaluate the safety and effectiveness of the filling stent graft system by animal experiments.Objective(1)According to the new design idea of anchoring in the aneurysm sac,a complete filling endograft system integrating covered stent with a surrounded endobag,filling agent and delivery system is manufactured to meet the needs of endovascular treatment for ascending aortic aneurysm.(2)In vitro model experiments were carried out to evaluate the feasibility of the filling endograft system,and initially verify that the anchoring force provided by the filling endograft is not inferior to the traditional endograft.(3)To construct a mature animal model of ascending aortic aneurysm and to evaluate the long-term stability of the animal model.(4)Endovascular treatment for the animal models of ascending aortic aneurysm were conducted with the filling endograft system to evaluate the safety and effectiveness of the novel endograft system.Methods(1)Development of a novel ascending aortic filling endograft system: Using nickel titanium alloy wire,the spiral PTFE covered stent and Z shaped cell terylene covered stent were made.A semi-compliant and wear-resistant polyurethane film were cutt and thermally shaped to make a surrounded balloon.A leakproof filling tube was designed.Endograft body was then produced by bonding above components together using light cured resin glue.A current endograft delivery system was improved with a small filling catheter and a semi-releasing device integrated in.The compression and installation method for the graft was also explored.Based on the previously selected two-component addition liquid silicone rubber,we adjusted the ratio of base polymer,reinforcing filler,crosslinking agent and catalyzer and catalytic activity regulator to obtain a kind of useful filling agent.On the premise of maintaining its mechanical properties,we reduced the viscosity,adjusted the curing time,and made it radiopaque using the tantalum powder.The mass fraction of tantalum powder was adjusted to get the optimum radiopacity.(2)In vitro simulation experiment: The silicone model was printed based on the aortic anatomical parameters of the experimental animals(pigs)with 3D printing technique.Through the X-ray fluoroscopy on the 3D model,endovascular procedures using filling endograft were completed via transapical access,which contained locating,releasing,filling,and withdrawing.Under X-ray,CT scan and direct view,the location,shape and the lumen patency of the endograft were observed.At the same time,the following information was recorded: to what extent the aneurysm was filled by the balloon,whether there was residual cavity in the aneurysm and whether the coronary artery and the superior branch artery were covered.The overall process of the endovascular procedures was also evaluated: whether the graft was introduced smoothly,whether the location and release was accurate,whether the delivery system was disconnected and withdrawed smoothly,whether the filling process was simple and controllable,whether the filling path was tight connected and leak-less,and whether the catheter was removed smoothly after filling.Further,the anchoring force of filling endograft and common tube endograft on ascending aortic aneurysm model was tested by tensometer to verify the feasibility of filling endograft system.(3)Construction of animal model of ascending aortic aneurysm: Twelve healthy adult pigs were selected as experimental animals.Under general anesthesia,an aneurysm-like bag with glutaraldehyde treated bovine pericardium patch was sutured to the anterior wall of ascending aorta.With wall clipping,the aortic wall was cut off as much as possible so that the aorta and the aneurysm of bovine pericardium patch can connect and form an aneurysm.Intraoperative angiography was performed to observe the morphology of aneurysm.Postoperative blood flow velocity was detected by ultrasonography.The dynamic change of aneurysm was observed by following-up CTA.The diameter of aneurysm,the diameter and length of the proximal and distal landing zone were measured and analyzed.Based on analysis of above data,the animal models were evaluated and determined whether they can be used to verify the safety and effectiveness of filling endograft.(4)Animal study of the filling endografts: After successful construction of ascending aortic aneurysm animal models in another twelve healthy adult pigs,endovascular repair of ascending aortic aneurysm using filling endograft was performed via transapical access.During the operation,angiography was used to observe whether the filling endograft was migrated,whether the aneurysm was excluded completely without endoleak and whether the important branch vessels were patent.After the operation,the experimental animals were followed up.The changes of the aneurysm and endograft were observed by CTA.The aortic valve function and cardiac function were detected by cardiac ultrasound.Finally,the animals were executed and the ascending aorta and endograft were taken for gross anatomy and pathological observation.Based on analysis of above data,the safety and effectiveness of the endograft system in the perioperative and follow-up period were evaluated.Results(1)The complete new filling stent graft was successfully made containing all the necessary components.The diameters of the stents were 30 mm and 35 mm,and length was 25 mm.The balloon diameter was 40 mm.An improved delivery system was made,with multiple function elements integrated,such as filling channel,semi-release device and so on.Two-component addition liquid silicone rubber was improved.The viscosity of A component was 27.1 mPa.s and B was 42.2 mPa.s.The mechanical properties of the cured silicone rubber were tensile strength of 1.05 MPa,elongation of 110%,tear strength of 3.13 kN/m,which could met the use requirement.The optimal mass/volume fraction of tantalum powder was determined to be 1g/ml,with which the liquid silicone rubber can obtain favorable radiopacity.(2)The process of introducing,releasing,filling and withdrawing of the endograft system were successful completed in vitro model.The position and shape of the stent graft was good.The outer membrane of the surrounded balloon was intact.The balloon could comply with sac of the aneurysm and fill with the cavity,without covering the ostia of the coronary arteries and the supra-arch vessels.The filling process was smooth,without leakage of filling agent.The filling time was 2.3±0.9 min,and the usage of filling agent was 7.8±2.7 ml.In an in vitro model,the ultimate displacement resistance force of the filling endografts was greater than that of the normal tube type endografts with oversizing of 6.7%(20.7±3.0N vs 3.95±0.7N,p<0.01)and 16.7%(20.7±3.0N vs 6.55±1.3N,p<0.01).(3)Using bovine pericardium suture,ascending aortic aneurysm model were successfully established in 10 pigs.The diameter of aneurysm neck was 22.6± 5.2 mm.The length of proximal landing zone was 10.7 ± 3.1 mm and the length of distal landing zone was 1.0 ± 1.3 mm.The diameter of the ascending aorta was 26.43 ± 1.52 mm before operation.The diameter of ascending aortic aneurysm was 46.62 ± 1.95 mm(p<0.05)after operation,which was 1.77 times that of the normal ascending aorta.During follow-up period,CT showed a slight increase in aneurysm diameter.Gross anatomy showed that the inner wall of the aneurysm was smooth,similar to the autologous aortic lumen.HE staining showed that the pericardium patch was covered by fibroblasts and collagen fibers,and the lumen was covered with new endothelial cells.There was no significant change in cardiac function of experimental animals during the follow-up period,as the ultrasound showed.(4)Of another twelve ascending aortic aneurysm animal models,eight animals successfully received the endovascular repair using filling stent graft system and survived.In 2 animals,stent grafts immigrated distal to the aortic arch.In one animal,the left coronary artery was covered leading to fatal ventricular fibrillation,while the last animal died from anesthesia accident in the process of closing chest.In the 8 animals surviving the procedure,no immigration or endoleak was observed during follow-up.The diameter of aneurysm did not change significantly(47.2±4.0mm vs 48.3±2.4mm,P=0.218),and the coronary arteries and supra-arch branches were patent.Ultrasound showed the aortic valve function,blood flow velocity in ascending aorta,and cardiac function were normal and did not change significantly.Gross anatomy and pathological observation revealed that the endothelium of the aortic wall was intact without significant injury.Scanning electron microscope showed that the surface of endograft was covered with fibrous tissue.ConclusionThe new filling stent graft system is feasible for the treatment of ascending aortic aneurysm.It can be successfully applied to treat the ascending aortic aneurysm model with insufficient landing zone.The perioperative and follow-up period results showed that the therapeutic effect was satisfactory.The safety and effectiveness of the stent-graft system was initially confirmed.The development and related experimental results of this new endograft system may provide new ideas for endovascular treatment of ascending aortic aneurysm,and provide a reference for future clinical trial.However,further optimization and improvement of the stent-graft is still needed according to the shortages found in the experiments.