Development of a radiopaque, long-term drug eluting bioresorbable stent for the femoral-iliac artery

Abstract

Tubular tissues exist in various forms purported for blood supply, waste secretion, etc. to aid proper function and maintenance of the human body. Under pathological conditions, however, these tissues may undergo stenosis. A major surgical treatment for stenosis is to implant a medical device called a stent which aims to expand the narrowed tissue and maintain its patency. Most stents are currently made from metals; despite their high mechanical strength, however, interactions with the host tissue often results in restenosis and stent fracture. To solve these problems, a bioresorbable stent (BRS) is proposed as a next generation stent. In this study, a rotating rod combined 3D printing system was developed to fabricate various types of BRSs. In addition, we confirmed that a 1.5 year long-term release of paclitaxel is possible using polymeric materials. Moreover, a stent loaded with contrast powder was fabricated and was successfully viewed under fluoroscopy. The stent was then implanted in the iliac arteries of pigs and no adverse events were observed for up to 8 weeks.

Fig. 1. Schematic image of this research. First, the materials used for printing are homogeneously mixed, delivered in a syringe, and mounted on 2RPS. Heat is applied to the syringe to melt the materials inside, and is extruded through the nozzle using pneumatic pressure. At the same time, the syringe moves based on the G-code so that the material can be printed at the desired location. Through this process, various forms of stents can be produced.

Fig. 2. (A) CAD image of Rotating rod combined 3D printing system (2RPS), (B) established whole system of 2RPS, (C) heating unit of 2RPS, (D) rotating unit of 2RPS, (E) various line width of stent (left: 300 μm/mid: 450 μm/right: 600 μm), (F) various wall thickness of stent (left: 200 μm/mid: 300 μm/right: 500 μm), (G) 12-peak stent with different stent diameter (left: 8 mm, right: 3 mm), (H) 6-peak stent with different stent diameter (left: 8 mm, right: 3 mm), (I and J) open cell type stent, (K) closed and open cell hybrid stent, (L) tubular type stent, (M) coil type stent, (N) coil, mesh hybrid stent, (O) protrusion surface imbedded stent for preventing migration, (P) various size of dumbbell type stent.

Fig. 3. Difference of the radial force of BRSs according to strut length (A) and degree (B).

Fig. 4. (A) Heat resistance test of paclitaxel. Top: non-heated/middle: 8 h 120 °C heated/bottom: 8 h 200 °C. (B) 1.5 years release profile of paclitaxel from BRS.

Fig. 5. Fluoroscopic image of contrast powder loaded BRS. (A) 5, 10, 15% iohexol loaded BRS. Visibility of the BRS (B) when covered with hand and (C) after washing (bottom).

Fig. 6. (A) Implanted BRS is visible under fluoroscopy in the right iliac artery of porcine. (B) Peripheral angiography shows that BRS is located in the right iliac artery.

Fig. 7. Cross section of the iliac artery show good apposition of BRS. H&E staining confirmed the neointimal proliferation and absence of stent restenosis (Scale bar: 500 μm).