Magnetic and Biocompatible Polyurethane Nanofiber Biomaterial for Tissue Engineering

Abstract

Recruitment of endothelial cells to cardiovascular device surfaces could solve issues of thrombosis, neointimal hyperplasia, and restenosis. Since current targeting strategies are often nonspecific, new technologies to allow for site-specific cell localization and capture in vivo are needed. The development of cytocompatible superparamagnetic iron oxide nanoparticles has allowed for the use of magnetism for cell targeting. In this study, a magnetic polyurethane (PU)-2205 stainless steel (2205-SS) nanofibrous composite biomaterial was developed through analysis of composite sheets and application to stent-grafts. The PU nanofibers provide strength and elasticity while the 2205-SS microparticles provide ferromagnetic properties. Sheets were electrospun at mass ratios of 0-4:1 (2205-SS:PU) and stent-grafts with magnetic or nonmagnetic stents were coated at the optimal ratio of 2:1. These composite materials were characterized by microscopy, mechanical testing, a sessile drop test, magnetic field measurement, magnetic cell capture assays, and cytocompatibility after 14 days of culturing with endothelial cells. Results of this study show that an optimal ratio of 2:1 2205-SS:PU results in a hydrophobic material that balanced mechanical and magnetic properties and was cytocompatible up to 14 days. Significant cell capture required a thicker material of 0.5 mm thickness. Stent-grafts fabricated from a magnetic coating and a magnetic stent demonstrated uniform cell capture throughout the device surface. This novel biomaterial exhibits a combination of mechanical and magnetic properties that enables magnetic capture of cells and other therapeutic agents for vascular and other tissue engineering applications.

Keywords: electrospinning; magnetic biomaterials; magnetic cell targeting; nanofibers; vascular stent-grafts.

FIG. 1.

Electrospun nanofibers. Representative images of Taylor cones (A–E) for solution ratios of 2205-SS:PU, light microscopy (F–J, scale bar 1000 μm), and scanning electron microscopy (K–O, scale bar 100 μm) of collected electrospun fibers. PU, polyurethane; SS, stainless steel.

FIG. 2.

Nanofiber materials. Morphology of collected electrospun PU fibers at variable flow rates: 0.010 mL/min (A–C), 0.009 mL/min (D–F), 0.008 mL/min (G–I) and 0.007 mL/min (J–L). Mandrel is oriented with end distal to the motor on the right-hand side.

FIG. 3.

Mechanical testing. Mechanical properties of electrospun sheets, including average engineering stress versus average engineering strain (A), ultimate tensile strength (B), stiffness (C), and ultimate strain (D). No significant differences were seen between groups for ultimate tensile strength, but trended downward with increasing concentration of 2205-SS (B). There was a significant difference (*p < 0.05) between the 4:1 and PU groups for ultimate strain.

FIG. 4.

Retained magnetic field. Magnetic properties of varying concentration of 2205-SS:PU electrospun sheets. Measurements were taken relative to background measurement (A–E) and after magnetization. Gross conformational changes were seen with increasing concentration of 2205-SS (F–J). Significant differences between groups (*p < 0.05) were observed both without (K) and with (L) normalization to thickness of each sheet.

FIG. 5.

Cell capture study. Cell capture capabilities (A–D) were assessed for thick (0.5 mm) and thin (0.1 mm) PU and 2:1 2205-SS:PU sheets. Cells are labeled red. Thicker 2:1 sheets showed significantly higher (*p < 0.05) magnetic properties relative to the thin sheets and the PU sheets (E). Thicker 2:1 sheets also captured significantly more cells relative to all other groups (F). Scale bars are 1000 μm. Color images are available online.

FIG. 6.

Cytotoxicity study. BOECs were seeded onto sheet material surfaces and demonstrated continued viability at days 7 (A–E) and 14 (F–J) for all material compositions. Live cells are stained green and dead cells are stained red. Scale bars are 1000 μm. BOECs, blood outgrowth endothelial cells. Color images are available online.

FIG. 7.

Stent-graft fabrication. Representative images of creation of stent-grafts with inner (A) and outer (B) layers. Mandrel is oriented with end distal to the motor on the right-hand side.

FIG. 8.

Stent-graft mechanical testing. Crush force data for stent-grafts with magnetic electrospun coatings (A). No significant differences were seen for crush force between magnetic and nonmagnetic stent-grafts. Crimping (B) and expansion (C) of stent-grafts on a balloon catheter. These devices were able to crimp and expand on a balloon catheter without fracture to the struts, puncturing through, tearing of, or delimitation of the PU/2205 cover. Scale ticks are 1 mm apart. Color images are available online.

FIG. 9.

Stent-graft retained magnetic field. Magnetic measurements were taken from 0° to 315° around the circumference of stent-grafts. 2205-SS and 316L-SS stent-grafts showed significant differences (*p < 0.05) at all angles other than 135° and 315°. Color images are available online.

FIG. 10.

Stent-graft cell capture. Microscopy images of cell capture to the surface of stent-grafts (A, B). Cells are labeled red. 2205-SS stent-grafts captured significantly more cells than 316L-SS stent-grafts (***p < 0.05) (C). Scale bars are 1000 μm. Color images are available online.