Modifying shape memory polymers to improve visualization during in vivo imaging

Shape memory polymers (SMPs) are highly adaptive materials with the ability to temporarily change shape in response to a specific external stimulus, before then returning to their original unique shape. An SMP can lose its rigidity and become very elastic, at which point it will recover its “memorized” shape if it is not restrained.

While in this elastic state, it can be elongated, folded or otherwise configured, without degrading. This versatility combined with the biocompatibility of these materials means SMPs have garnered much interest for their potential use in biomedical applications, especially as materials for minimally invasive procedures and tissue scaffolds.

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Polyurethane SMPs

Polyurethane SMPs are of particular interest due to their excellent biocompatibility. These SMPs can be processed to form highly porous, low density foams that have enhanced shape memory effect due to their higher compressibility. Polyurethane SMPs have been proposed as minimally invasive medical materials in a number of applications including peripheral occlusion, arterial occlusion and coronary and vascular grafts. However, although SMP foams show great promise as a potential biomaterial, they are limited by a lack of visibility during in vivo imaging.

X-ray fluoroscopy risks

Clinically, the most commonly used imaging technique is X-ray angiography using fluoroscopy. Fluoroscopy involves an X-ray beam being passed through the body to transmit a continuous image to a monitor so that an instrument or contrast agent can be visualized as it moves through the body. For complex surgical interventions, such as stent implantation, the ionizing radiation dose is relatively high because it needs to be administered over a long period.

This radiation exposure is associated with the immediate risk of skin or underlying tissue being “burnt,” as well as the longer-term risk of radiation-related cancer. The development of biomaterials with enhanced optical properties that do not require fluoroscopy would therefore be highly advantageous.

Fluorescence as an alternative

Fluorescence-guided procedures are frequently used in eye tests such as retinal angiography, where a yellow dye called fluorescein is injected into the eye and a camera used to examine blood flow in the retina. The fluoresceins and near-infrared (NIR) dyes used for such procedures have shown excellent biocompatibility and clearance by the body. They continue to improve clinical outcomes and are becoming increasingly popular in a number of applications.

Modifying SMPs to improve visualization

Fluorescent dyes are now employed in polymer systems for temperature/chemical sensors and monitors, as well as particle imaging, yet they are not commonly used in SMPs that serve as biomaterials in medical devices. Using fluorescence to enhance the optical properties of SMPs could yield a highly valuable biomaterial that can be visualized through blood and solid tissue during in vivo imaging.

To investigate, Andrew Weems (Biomedical Device Laboratory, exas A&M University) and colleagues covalently incorporated four fluorescent dyes into SMP polyurethane foams by crosslinking them into the polymer backbone. The dyes used to modify the SMPs were phloxine B (PhB), eosin Y (Eos), indocyanine green (IcG) and calcein (Cal), although the study did demonstrate that the methods could be applied to other dyes that possess similar functional groups.

The ALPHA infrared spectrometer from Bruker was used to take ATR-FTIR spectra, which were examined using Bruker’s Opus software to identify peaks and perform baseline and atmospheric corrections.

The Bruker In-Vivo Xtreme multimodal preclinical imaging system was used to take X-ray and fluorescent images of each sample and the images were processed using Bruker’s molecular imaging software. The In-Vivo Xtreme is an extremely versatile, sensitive, and fast preclinical imaging device that combines X-ray fluorescence, luminescence, radioisotopic modalities into one high throughput, easy to use system.

Weems and team were able to demonstrate that incorporation of the dyes into SMP polyurethane foams was possible, without significant alteration of the material’s shape memory or thermomechanical properties.

PhB demonstrated the most potential as an SMP modifier. Qualitative analysis of foams containing PhB showed that 0.5% PhB loading gave the most intense fluorescence and quantitative analysis revealed that PhB enabled visualization through 1 cm of blood and through soft tissue.

The authors say this fluorescent biomaterial system shows great promise as a medical material. It could allow for optical visualization through blood and soft tissue, without the need for harmful X-ray or radiation methods, thereby offering an alternative means of viewing implanted devices and materials.

References

  • Weems, A et al. Shape memory polymers with visible and near-infrared imaging modalities: synthesis, characterization and in vitro analysis. RSC Adv., 2017;7: 19742-19753
  • Weems, A et al. Shape memory polymers with enhanced visibility for magnetic resonance- and X-ray imaging modalities. Acta Biomater, 2017; 54: 45-57. DOI: 10.1016/j.actbio.2017.02.045.
  • Chan, B et al. Recent Advances in Shape Memory Soft Materials for Biomedical Applications. ACS Appl. Mater. Interfaces, 2016, 8 (16), pp 10070–10087. DOI: 10.1021/acsami.6b01295
  • Santo, L. Shape memory polymer foams. Progress in Aerospace Sciences, 2016;81:60-65. DOI: 10.1016/j.paerosci.2015.12.003
  • YeeShan, W et al. Biomedical applications of shape-memory polymers: how practically useful are they? Science China Chemistry, 2014; 57(4): 476-489. DOI: 10.1007/s11426-013-5061-z
  • Eurekalert. Biomedical applications of shape-memory polymers: How practically useful are they?
  • SCIENCE CHINA PRESS. Available at: https://www.eurekalert.org/pub_releases/2014-04/scp-bao041714.php
  • CRG. Shape Memory Polymers. Available at: http://www.crgrp.com/rd-center/shape-memory-polymers
  • American Food & Drug Administration. Fluoroscopy. Available at: https://www.fda.gov/radiation-emittingproducts/radiationemittingproductsandprocedures/medicalimaging/medicalx-rays/ucm115354.htm

About Bruker

Bruker is market leader in analytical magnetic resonance instruments including NMR, EPR and preclinical magnetic resonance imaging (MRI). Bruker's product portfolio in the field of magnetic resonance includes NMR, preclinical MRI ,EPR and Time-Domain (TD) NMR. In addition.

Bruker delivers the world's most comprehensive range of research tools enabling life science, materials science, analytical chemistry, process control and clinical research. Bruker is also the leading superconductor magnet and ultra high field magnet manufacturer for NMR and MRI solutions.


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Last updated: Sep 28, 2017 at 6:36 AM

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