Characterization of Partially Covered Self-Expandable Metallic Stents for Esophageal Cancer Treatment: In Vivo Degradation

Abstract

Partially covered self-expandable metallic esophageal stent (SEMS) placement is the most frequently applied palliative treatment in esophageal cancer. Structural characterization of explanted 16 nitinol-polyurethane SEMS (the group of 6 females, 10 males, age 40-80) was performed after their removal due to dysfunction. The adverse bulk changes in the polymer structure were identified using differential scanning calorimetry (DSC), differential mechanical thermal analysis (DMTA), and attenuated total reflectance infrared spectroscopy (ATR-IR) and discussed in terms of melting point shift (9 °C), glass-transition shift (4 °C), differences in viscoelastic behavior, and systematic decrease of peaks intensities corresponding to C-H, C═O, and C-N polyurethane structural bonds. The scanning electron and confocal microscopic observations revealed all major types of surface degradation, i.e., surface cracks, peeling off of the polymer material, and surface etching. The changes in the hydrophobic polyurethane surfaces were also revealed by a significant decrease in wettability (74°) and the corresponding increase of the surface free energy (31 mJ/m²). To understand the in vivo degradation, the in vitro tests in simulated salivary and gastric fluids were performed, which mimic the environments of proximal and distal ends, respectively. It was concluded that the differences in the degradation of the proximal and distal ends of prostheses strongly depend on the physiological environment, in particular stomach content. Finally, the necessity of the in vivo tests for SEMS degradation is pointed out.

Keywords: biomaterial; esophageal cancer; esophageal stent; esophagus; in vivo degradation; polyurethane.

Figure 1

DSC profiles and the characteristic T_melt values for proximal (a) and distal (b) ends of SEMS polyurethane cover. The inset in (b) shows a narrow range of T_melt for the distal end of the prostheses.

Figure 2

Changes of T_melt with implantation time for proximal (▲) and distal (■) ends of SEMS polyurethane (colors represent patients’ treatment: blue, chemotherapy; green, chemo- and radiotherapy; orange, palliative treatment only, i.e., stenting).

Figure 3

Storage modulus, E′ (a), loss modulus, E″ (b), and tan δ (c) profiles for the proximal end of SEMS polyurethane covers.

Figure 4

Storage modulus, E′ (a), loss modulus, E″ (b), and tan δ (c) profiles for the distal end of SEMS polyurethane covers.

Figure 5

ATR-IR spectra of SEMS polyurethane covers: reference sample and selected stents (proximal end).

Figure 6

ATR-IR spectra of SEMS polyurethane covers: reference sample and selected stents (distal end).

Figure 7

Representative images of reference sample morphology of SEMS polyurethane cover: outer side (a) and inner side (b) of the stent.

Figure 8

Representative SEM images of SEMS polyurethane covers with visible surface damages appearing after 9–12 weeks implantation time.

Figure 9

Representative SEM images illustrating the surface degradation (prosthesis 16) for the proximal end of the esophageal implant (a) and for parallel in vitro experiment in artificial saliva for 2 months (b).

Figure 10

Representative SEM images illustrating the surface degradation (prosthesis 8) for the distal end of the esophageal implant (a) and for in vitro experiment in simulated gastric fluid for 2 months (b).

Figure 11

Surface roughness (parameterized by R_a) as a function of incubation in simulated body fluid (gastric and salivary) together with graphical representations showing the changes in surface topography.

Figure 12

Representative results of water contact angle measurements and the corresponding surface free energy for the investigated SEMS polyurethane covers (a): reference (navy blue) and implanted prostheses (blue). The shadowing illustrates the range of experimental values for the investigated samples. Detailed analysis of water contact angle measurements as a function of time in the human body (b).