Shape memory polymers with enhanced visibility for magnetic resonance- and X-ray imaging modalities

Abstract

Currently, monitoring of minimally invasive medical devices is performed using fluoroscopy. The risks associated with fluoroscopy, including increased risk of cancer, make this method especially unsuitable for pediatric device delivery and follow-up procedures. A more suitable method is magnetic resonance (MR) imaging, which makes use of harmless magnetic fields rather than ionizing radiation when imaging the patient; this method is safer for both the patient and the performing technicians. Unfortunately, there is a lack of research available on bulk polymeric materials to enhance MR-visibility for use in medical devices. Here we show the incorporation of both physical and chemical modifying agents for the enhancement of both MR and X-ray visibility. Through the incorporation of these additives, we are able to control shape recovery of the polymer without sacrificing the thermal transition temperatures or the mechanical properties. For long-term implantation, these MR-visible materials do not have altered degradation profiles, and the release of additives is well below significant thresholds for daily dosages of MR-visible compounds. We anticipate our materials to be a starting point for safer, MR-visible medical devices incorporating polymeric components.

Statement of significance: Shape memory polymers (SMPs) are polymeric materials with unique shape recovery abilities that are being considered for use in biomedical and medical device applications. This paper presents a methodology for the development of MR and X-ray visible SMPs using either a chemically loaded or physical loaded method during polymer synthesis. Such knowledge is imperative for the development and clinical application of SMPs for biomedical devices, specifically for minimally-invasive vascular occlusion treatments, and while there are studies pertaining to the visibility of polymeric particles, little work has been performed on the utility of biomaterials intended for medical devices and the impact of how adding multiple functionalities, such as imaging, may impact material safety and degradation.

Keywords: Cytocompatibility; Magnetic resonance imaging; Shape memory polymer; X-ray imaging.

Figure 1

Pore diameter comparisons of MR-visible SMPs, displaying pore sizes of Fe (A) and Gd (B) containing SMPs. The relative isotropicity of the pores is displayed in panel C. SEMs of MR-visible SMPs are displayed; (D) no additive, (E) 1.0% Gd, (F) 5.0% Fe.

Figure 2

Mechanical properties of MR-visible SMPs, displaying elastic moduli (A), strain at break (B), ultimate tensile strength (C), and toughness (D) of selected formulations. (n=8) * indicates statistical difference compared with the control SMPs (p< 0.05).

Figure 3

Shape recovery of SMPs at 50°C examined over 30 minutes. (n=3)

Figure 4

MR-imaging characerization of SMPs using both T1 (A, C) and T2 (B, D) weighted imaging. Actual diameter of sample is represented in C as a dotted red line. * indicates statistical difference compared with the control SMPs (p< 0.05).

Figure 5

X-ray density of MRI-visible SMPs; (A) Iron oxide–doped SMP in crimped state, (B) Iron oxide–doped SMP in expanded state, (C) Gadolinium chelate–doped SMP in crimped state, (D) Gadolinium chelate–doped SMP in expanded state. (E) The x-ray image of the expanded and crimped SMPs along with the control nylon rod; an example of the regions of interest is denoted by a white box. * indicates statistical difference compared with the control SMPs (p< 0.05).

Figure 6

An approximation of dose per day of MR contrast agents determined from ICP analysis of metals extracted from degraded SMPs. (A) No Additive SMP, (B) 0.5% Gd SMP, (C) 1.0% Gd SMP, (D) 1.0% Fe SMP, (E) 5.0% Fe SMP. Gravimetric changes of the bulk material (F) and the change in gel fraction were also examined (insert, F) over the same four-week period. (n=7)

Figure 7

SEM images of original (A–C) and degraded SMPs at four weeks (D–F), displaying the difference between the control (A, D), 5.0% Fe (B, E), and 1.0% Gd (C,F) SMPs.

Figure 8

10x images acquired of GFP-expressing 3T3s on control discs (A, E), 1% Gd discs (B,F), 5% Fe discs (C,G), and TCPS wells (D,H) 24 (A–D) and 72 (E–H) hours after seeding (J). Increases in relative fluorescence units (RFU) per cm² after 3-hour incubation with 5% resazurin solution for GFP-expressing 3T3s 24 and 72 hours after seeding on control discs (Ctrl), 1% Gd discs, 5% Fe discs, or TCPS wells. * indicates statistical difference compared with the control SMPs (p< 0.05).

Figure 9

An idealized schematic illustration presenting the initial surface hydroxyl groups of the Fe nps, the integration of the nps into the urethane network via reaction of the isocyanates with surface hydroxyls, and the degradation and subsequent dissolution of the particle with urethane linkages and primary amine or aldehyde endgroups due to network oxidation. Yellow denotes hydroxyl groups, blue denotes urethane linkages, green is tertiary amine linkages, and red indicates primary amine or aldehyde endgroups.