Role of polymers in the design of 3D carbon nanotube-based scaffolds for biomedical applications

Since pioneer works by Iijima in 1991, carbon nanotubes (CNTs) have received a great deal of attention as confirmed by the increasing number of papers in the topic. Their unique and attractive properties have made them extensively demanded materials for a wide variety of technological applications, including their promising use as scaffolds in tissue engineering. In this review, we focus on the role that polymers (both natural and synthetic) play on the fabrication of three-dimensional (3D) CNT-based scaffolds for biomedical applications, with emphasis on biocompatible fabrication strategies such as freeze-casting, electrospinning and gel formation. These 3D matrices may be an interesting and alternative platform to circumvent structural limitations and toxicity problems of bare CNTs by the use of biocompatible dispersant polymers that allow the preparation of substrates better resembling native extracellular matrices. In any case, due to the relevance of CNT toxicity in this context, we also discuss significant works concerning cell and tissue responses to CNTs in dispersion, highlighting: (1) the asbestos-like behavior of CNTs, (2) surface functionalization as a tool to reduce CNT toxicity and (3) CNT biodistribution from the blood stream and posterior excretion. In this sense, literature revision has evidenced major toxicity issues related to: (a) the inherent insolubility and tendency to aggregate of pristine CNTs, (b) the rigidity of their structures that makes them resemble asbestos, (c) the presence of residual metal impurities or amorphous carbon from their synthesis, and (d) the depletion of culture media components due to the adsorptive properties of CNTs. Nevertheless, as expected for almost any material, we also illustrate how dose plays a key role in the biological responses induced. Overall, this critic review is expected to help research community working on polymers and CNTs, as well as other carbon nanomaterials such as graphene, to identify useful guidelines that help advancing the use of 3D CNT-based scaffolds in biomedical applications. (C) 2014 Elsevier Ltd. All rights reserved.