Magnetic and Biocompatible Polyurethane Nanofiber Biomaterial for Tissue Engineering.

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.

A new way to visualize prostate brachytherapy needles using ultrasound color Doppler and needle surface modifications.

PURPOSE: Suboptimal ultrasound conspicuity of the brachytherapy applicator can lead to inaccurate image reconstructions of the applicator resulting in decreased tumor control or increased normal tissue dose. This feasibility study aims to improve ultrasound conspicuity of high-dose rate (HDR) brachytherapy needles by modifying the surface of the needles to produce a color Doppler twinkling signature. MATERIALS AND METHODS: Surface modifications of standard 17-gauge titanium HDR brachytherapy needles included laser-scribing, application of polymethyl methacrylate (PMMA), and coating with a commercially available echogenic coating. Laser-scribing was performed with variable widths (0.1-1 mm) and depths (10-100 µm). The echogenic coating was applied with 3 different thicknesses (27, 40, and 64 µm). Unmodified and modified needles were imaged under B-mode and color Doppler ultrasound in phantom and cadaver, and the signal strength was recorded. RESULTS: Laser-scribed, PMMA-coated, and echogenic-coated brachytherapy needles produced a twinkling signature along the needle shaft on color Doppler ultrasound. Twinkling was observed with laser-scribe depths >20 µm and widths >0.1 mm and from echogenic coatings 40 µm and 64 µm thick. Twinkling was not observed with unmodified needles. The twinkling signature had a spectral composition with a uniform magnitude between the velocities of 2 to 16 cm/s. CONCLUSIONS: Color Doppler ultrasound of surface-modified brachytherapy applicators may improve applicator conspicuity aiding applicator placement and digitization. HDR brachytherapy needles may be modified to produce the twinkling signature via laser-scribing, PMMA rings, or applying an echogenic coating.

Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker: a comparative investigation.

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored.

Nanoparticle-Mediated Cell Capture Enables Rapid Endothelialization of a Novel Bare Metal Stent.

Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic cell capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (Fe3O4) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled cells to 2205 SS stents. In this study, we show extensive endothelialization of magnetic 2205 SS stents (median 98.4% cell coverage) within 3 days, whereas the control 316L SS stents exhibited significantly less coverage (median 48.9% cell coverage, p < 0.0001). This demonstrates the ability of intracoronary delivery of magnetic nanoparticle labeled autologous endothelial cells to improve endothelialization of magnetized coronary stents within 3 days of implantation.

Fabrication of Small Caliber Stent-grafts Using Electrospinning and Balloon Expandable Bare Metal Stents.

Stent-grafts are widely used for the treatment of various conditions such as aortic lesions, aneurysms, emboli due to coronary intervention procedures and perforations in vasculature. Such stent-grafts are manufactured by covering a stent with a polymer membrane. An ideal stent-graft should have a biocompatible stent covered by a porous, thromboresistant, and biocompatible polymer membrane which mimics the extracellular matrix thereby promoting injury site healing. The goal of this protocol is to manufacture a small caliber stent-graft by encapsulating a balloon expandable stent within two layers of electrospun polyurethane nanofibers. Electrospinning of polyurethane has been shown to assist in healing by mimicking native extracellular matrix, thereby promoting endothelialization. Electrospinning polyurethane nanofibers on a slowly rotating mandrel enabled us to precisely control the thickness of the nanofibrous membrane, which is essential to achieve a small caliber balloon expandable stent-graft. Mechanical validation by crimping and expansion of the stent-graft has shown that the nanofibrous polyurethane membrane is sufficiently flexible to crimp and expand while staying patent without showing any signs of tearing or delamination. Furthermore, stent-grafts fabricated using the methods described here are capable of being implanted using a coronary intervention procedure using standard size guide catheters.

Cell Labeling and Targeting with Superparamagnetic Iron Oxide Nanoparticles.

Targeted delivery of cells and therapeutic agents would benefit a wide range of biomedical applications by concentrating the therapeutic effect at the target site while minimizing deleterious effects to off-target sites. Magnetic cell targeting is an efficient, safe, and straightforward delivery technique. Superparamagnetic iron oxide nanoparticles (SPION) are biodegradable, biocompatible, and can be endocytosed into cells to render them responsive to magnetic fields. The synthesis process involves creating magnetite (Fe3O4) nanoparticles followed by high-speed emulsification to form a poly(lactic-co-glycolic acid) (PLGA) coating. The PLGA-magnetite SPIONs are approximately 120 nm in diameter including the approximately 10 nm diameter magnetite core. When placed in culture medium, SPIONs are naturally endocytosed by cells and stored as small clusters within cytoplasmic endosomes. These particles impart sufficient magnetic mass to the cells to allow for targeting within magnetic fields. Numerous cell sorting and targeting applications are enabled by rendering various cell types responsive to magnetic fields. SPIONs have a variety of other biomedical applications as well including use as a medical imaging contrast agent, targeted drug or gene delivery, diagnostic assays, and generation of local hyperthermia for tumor therapy or tissue soldering.

Design and validation of a novel ferromagnetic bare metal stent capable of capturing and retaining endothelial cells.

Rapid healing of vascular stents is important for avoiding complications associated with stent thrombosis, restenosis, and bleeding related to antiplatelet drugs. Magnetic forces can be used to capture iron-labeled endothelial cells immediately following stent implantation, thereby promoting healing. This strategy requires the development of a magnetic stent that is biocompatible and functional. We designed a stent from the weakly ferromagnetic 2205 stainless steel using finite element analysis. The final design exhibited a principal strain below the fracture limit of 30% during crimping and expansion. Ten stents were fabricated and validated experimentally for fracture resistance. Another 10 stents magnetized with a neodymium magnet showed a magnetic field in the range of 100-750 mG. The retained magnetism was sufficiently strong to capture magnetically-labeled endothelial cells on the stent surfaces during in vitro studies. Magnetically-labeled endothelial cell capture was also verified in vivo after 7 days following coronary implantation in 4 pigs using histological analysis. Images of the stented blood vessels showed uniform endothelium formation on the stent surfaces. In conclusion, we have designed a ferromagnetic bare metal stent from 2205 stainless steel that is functional, biocompatible, and able to capture and retain magnetically-labeled endothelial cells in order to promote rapid stent healing.