Research and clinical translation of trilayer stent-graft of expanded polytetrafluoroethylene for interventional treatment of aortic dissection

Abstract

The aortic dissection (AD) is a life-threatening disease. The transcatheter endovascular aortic repair (EVAR) affords a minimally invasive technique to save the lives of these critical patients, and an appropriate stent-graft gets to be the key medical device during an EVAR procedure. Herein, we report a trilayer stent-graft and corresponding delivery system used for the treatment of the AD disease. The stent-graft is made of nitinol stents with an asymmetric Z-wave design and two expanded polytetrafluoroethylene (ePTFE) membranes. Each of the inner and outer surfaces of the stent-graft was covered by an ePTFE membrane, and the two membranes were then sintered together. The biological studies of the sintered ePTFE membranes indicated that the stent-graft had excellent cytocompatibility and hemocompatibility in vitro. Both the stent-graft and the delivery system exhibited satisfactory mechanical properties and operability. The safety and efficacy of this stent-graft and the corresponding delivery system were demonstrated in vivo. In nine canine experiments, the blood vessels of the animals implanted with the stent-grafts were of good patency, and there were no thrombus and obvious stenosis by angiography after implantation for 6 months. Furthermore, all of the nine clinical cases experienced successful implantation using the stent-graft and its postrelease delivery system, and the 1-year follow-ups indicated the preliminary safety and efficacy of the trilayer stent-graft with an asymmetric Z-wave design for interventional treatment.

Keywords: aortic dissection; clinical translation of biomaterials; delivery system for interventional treatment; expanded polytetrafluoroethylene; stent-graft.

Graphical abstract

Figure 1.

Schematic illustration of the AD formation and treatment. (A) Illustration of the process of AD formation. (B) The comparison of invasive thoracotomy and minimally invasive interventional treatment using an ePTFE stent-graft. The arrow in the interventional surgery illustration indicates the entry point of the delivery system. Key issues of the interventional device and corresponding design strategies are described in the bottom.

Figure 2.

Schematic presentation of fabrication of the ePTFE stent-graft with a trilayer structure. (A) The fabrication process of the ePTFE stent-graft. (B) Trilayer structure illustration of the stent-graft and SEM images of the ePTFE membrane before and after sintering. The ePTFE membrane before sintering exhibits node-fiber structure. As demonstration, a node is shown by the triangle, and a fiber is shown by the arrow.

Figure 3.

Physical and biological characteristics of the as-prepared ePTFE membrane of the stent-graft. (A) Tensile tests of sintered ePTFE membrane. (B) XRD pattern of the ePTFE membrane. (C) DSC curve of the ePTFE membrane, indicating that its melting point is 342°C. (D) Hydrophilicity test of the ePTFE membrane. (E) Cytotoxicity test of the ePTFE membrane. (F) Hemolysis test of the ePTFE membrane. The dashed lines in (E) and (F) indicate the criteria of the corresponding ISO standards to access in vitro biocompatibility of a medical device.

Figure 4.

Schematic diagram of the stent-graft and characterization of the stent-graft and delivery system. (A) Schematic diagram of the stent-graft and the superiorities of the stent-graft design. The connecting bar on the back of the stent-graft (as the arrow shown) provides the stent-graft with good supporting performance in the axial direction, and the mini Z-wave stents (as the triangle shown) on the lesser curvature side of the stent-graft provide the stent-graft with excellent compatibility to the aortic arch. (B) The measured radial forces of the stent-graft. (C) The release force and postrelease force of the delivery system when deploying the stent-graft. The measured release force of the stent-graft is <30 N and the measured postrelease force is <10 N, which indicate the feasibility for doctors to operate the delivery system.

Figure 5.

The postrelease delivery system and the implantation procedure. (A) Illustration of the delivery system. (B) Diagram of the stent-graft delivery process, including the enlarged view of the process steps of the stent-graft in the aorta and the flow chart of the operation of the delivery system outside the human body. (C) Schematic illustration of the comparison of the way of normal release and postrelease. In the normal release mode, the anchor position of the stent-graft may be changed due to the flush of the blood; and in the postrelease mode, the anchor position is firmly fixed by the anchor of the delivery system. (D) Illustration of the postrelease delivery system captured with and without stent-graft. The left picture demonstrates that the bare stent was captured by the anchor of the delivery system and the proximal end of the stent-graft cannot move during the stent-graft deployment; and the right picture demonstrates that the bare stent was released by withdrawing the anchor of the delivery system.

Figure 6.

Evaluation of the stent-graft in an interventional treatment in a canine model. (A) DSA images of an experimental canine model, including before, during and after stent-graft implantation. (B) HE staining images of implantation sites. The middle is a whole view of the cross-section in the stent-graft in the animal artery, which indicates good supporting performance of the stent and no thrombus in the lumen. The right is a local view at the site of Ni–Ti wire embraced by the ePTFE membrane, indicating the in-growth of smooth muscle cells and fibroblasts inside and outside the membrane. The left is a local view of the membrane and the vessel wall, showing a good fit between the membrane and the hyperplastic intima of the vessel. The hyperplastic tissue shows neovascularization and no inflammatory cell infiltration. The stent-graft was implanted in the animal’s aorta for 6 months.

Figure 7.

Global view of an ePTFE stent-graft and a demonstration of a human clinical case of a 66-year-old man. (A) Global view of an ePTFE stent-graft and schematic diagram of human intervention method. (B) DSA images of a human clinical case during various stages of the procedure.

Figure 8.

Human clinical case and follow-up evaluation. (A) Cross-section images of CTA after stent-graft implantation in an enrolled patient, including preoperation, 1 , 6 months and 1-year postoperation. (B) Three-dimensional reconstruction of CTA images of the same person, including preoperation, 1, 6 months and 1-year postoperation. (C) Statistical data analysis of the diameter changes of vascular FL after stent-graft implantation of nine patients with type B ADs, including the proximal, middle and distal FL diameters.