心室間隔缺損封堵器之研發與體外實驗

Abstract

心室間隔缺損是最常見的先天性心臟病，約占所有先天性心臟病的20%-30%，其中膜周部心室間隔缺損約占心室間隔缺損的60%，缺損較嚴重的患者可能出現心臟衰竭，甚至危及生命。心室間隔缺損的主要治療方式包括外科修補手術及介入式手術，介入式治療不論從手術時長、手術創傷及術後並發症等方面皆具有顯著優勢。本研究提出一項或能適用於發病率最高的膜周部心室間隔缺損介入式治療的微型醫療器材—心室間隔缺損封堵器，該器材植入體內後，能夠降低患者左右心室的血液分流量，並輔助缺損周圍的組織自主向內生長完成內皮化。 本研究開發出三款適用於膜周部心室間隔缺損的封堵器，分別為：單層編織封堵器、雙層編織封堵器及雙層覆膜封堵器。研究流程包含設計、製程有限元模擬、雛型品製造及體外實驗。首先是設計方面，藉由電腦輔助設計軟體，訂定設計參數並繪製出熱處理夾具及不同參數的編織支架；接著透過有限元素分析，確認製造過程中封堵器的機械性質,並確保其製造的可行性；雛型品製造方面，採用鎳鈦絲線進行編織後，再透過多次熱處理使支架定型成心室間隔缺損封堵器的形狀，並以焊接工藝進行收口。雙層編織心室間隔缺損封堵器是在編織角45°心室間隔缺損封堵器內再放置一個尺寸略小的封堵器，並進行焊接。雙層覆膜心室間隔缺損封堵器則是在編織角45°心室間隔缺損封堵器的基礎上，內置一個以靜電紡絲、真空燒結技術進行防水性覆膜的封堵器；最後在體外實驗方面，心室間隔缺損封堵器雛型品在推送管等輸送裝置的輔助下，能夠被順利的收進輸送導管中，並且能夠將封堵器順利釋放至指定缺損處，同時自動彈回預定形狀。流量實驗方面，單層編織、雙層編織、雙層覆膜三款心室間隔缺損封堵器的血液阻擋效率分別約為20%-30%、30%及60%，體現出心室間隔缺損封堵器在臨床上應用的可行性。

Ventricular septal defects are the most common form of congenital cardiac malformation, comprising 20%-30% of all congenital heart disease. 60% of these defects are perimembranous ventricular septal defect. Large defects can cause a range of disabilities, including heart failure even mortal danger. The standard treatments for ventricular septal defects include open-heart surgical closure and transcatheter closure. Percutaneous endovascular procedures are less invasive and can be done on a beating heart. In addition, interventional therapy has significant advantages in operating time, surgical trauma and postoperative complications. In this research, an implantable medical device, ventricular septal defect occluder for perimembranous ventricular septal defect, is proposed. By deploying ventricular septal defect occluder inside the defect, the device is able to reduce the blood flow between left ventricle and right ventricle. Also, it can assist the tissues around the defect to ingrow autonomously which can complete endothelialization. Through the design, simulation, manufacturing and In-vitro experiment processes, this research develop three different kinds of ventricular septal defect occluder:single-layered braided occluder,double-layered braided occluder and double-layered covered occluder. In the design process, the design parameters of braided stent and fixture are defined with the help of computer-aided design software. In the simulation process, the aim is to analyze the mechanical behavior of the devices. In order to confirm the braided stent will not be damage during manufacturing. In the manufacturing process, ventricular septal defect occluder is manufactured on nickel-titanium filaments with braided technology, followed by heating with fixture the device into the ventricular septal defect occluder shape and welding to close the occluder. The double-layer braided ventricular septal defect occluder is to place a smaller size occluder into the original occluder and weld it. The double-layer covered ventricular septal defect occluder is braided stent with waterproof membranes. Electrospinning technique is applied on the braided stent to produce membranes, followed by vacuum-sintering process to improve the waterproof property and mechanical behavior of membranes and place the covered occluder into the original occluder. Finally, in the experiment process, ventricular septal defect occluder can be successfully compressed into catheters and rebounded into the original shape in defect with delivery devices. The results of flow experiments show that the blocked efficiency of single-layered braided, double-layered braided and double-layered covered ventricular septal defect occluder about 20%-30%, 30% and 60%, respectively. Reflect the feasibility of ventricular septal defect occluder in clinical application.