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Aims: The addition of carbon nanotubes (CNTs) remarkably improves the mechanical characteristics of base materials. CNT/alumina ceramic composites are expected to be highly functional biomaterials useful in a variety of medical fields. Biocompatibility and bone tissue compatibility were studied for the application of CNT/alumina composites as biomaterials., Methods & Results: Inflammation reactions in response to the composite were as mild as those of alumina ceramic alone in a subcutaneous implantation study. In bone implantation testing, the composite showed good bone tissue compatibility and connected directly to new bone. An in vitro cell attachment test was performed for osteoblasts, chondrocytes, fibroblasts and smooth muscle cells, and CNT/alumina composite showed cell attachment similar to that of alumina ceramic., Discussion & Conclusion: Owing to proven good biocompatibility and bone tissue compatibility, the application of CNT/alumina composites as biomaterials that contact bone, such as prostheses in arthroplasty and devices for bone repair, are expected.

Multi-walled carbon nanotubes (MWCNTs) promote calcification during hydroxyapatite (HA) formation by osteoblasts. Primary cultured osteoblasts are incubated with MWCNTs or carbon black. After culture for 3 weeks, the degree of calcification is very high in the 50 μg mL(-1) MWCNT group. Transmission electron microscopy shows needle-like crystals around the MWCNTs, and diffraction patterns reveal that the peak of the crystals almost coincides with the known peak of HA., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.

Carbon nanotubes (CNTs) have already been successfully implemented in various fields, and they are anticipated to have innovative applications in medical science. However, CNTs have asbestos-like properties, such as their nanoscale size and high aspect ratio (>100). Moreover, CNTs may persist in the body for a long time. These properties are thought to cause malignant mesothelioma and lung cancer. However, based on conventional toxicity assessment systems, the carcinogenicity of asbestos and CNTs is unclear. The reason for late countermeasures against asbestos is that reliable, long-term safety assessments have not yet been developed by toxicologists. Therefore, a new type of long-term safety assessment, different from the existing methods, is needed for carbon nanomaterials. Recently, we applied a proteomic approach to the safety assessment of carbon nanomaterials. In this review, we discuss the basic concept of our approach, the results, the problems, and the possibility of a long-term safety assessment for carbon nanomaterials using the toxicoproteomic approach., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: In the present study, we investigated whether DJ-1 could serve as a biomarker for assessing the biocompatibility of multiwalled carbon nanotubes (MWCNTs), using the highly purified carbon nanotube, HTT2800., Methods: Using Western blot analysis, we determined DJ-1 protein levels in two different types of cells (one capable and the other incapable of HTT2800 endocytosis). Using quantitative real-time polymerase chain reaction, we also investigated the ability of purified nanotubes to alter DJ-1 mRNA levels., Results: We demonstrated that the DJ-1 protein concentration was reduced, regardless of the cytotoxic activity of intracellular HTT2800. Furthermore, HTT2800 decreased the DJ-1 mRNA levels in a dose-dependent manner. This decrease in DJ-1 mRNA levels was not observed in the case of Sumi black or cup-stacked carbon nanotubes., Conclusion: These data indicate that modification of DJ-1 expression is caused by the cell response to MWCNTs. We conclude that DJ-1 is a promising candidate biomarker for the development of biocompatible MWCNTs.

Although there have been many reports about the cytotoxicity of multi-walled carbon nanotubes (MWCNTs), the results are still controversial. To investigate one possible reason, the authors investigated the influence of MWCNT dispersants on cellular uptake and cytotoxicity. Cytotoxicity was examined (measured by alamarBlue(®) assay), as well as intracellular MWCNT concentration and cytokine secretion (measured by flow cytometry) in human bronchial epithelial cells (BEAS-2B) exposed to a type of highly purified MWCNT vapor grown carbon fiber (VGCF(®), Shōwa Denkō Kabushiki-gaisha, Tokyo, Japan) in three different dispersants (gelatin, carboxylmethyl cellulose, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine). The authors also researched the relationship between the intracellular concentration of MWCNTs and cytotoxicity by using two cell lines, BEAS-2B and MESO-1 human malignant pleural mesothelioma cells. The intracellular concentration of VGCF was different for each of the three dispersants, and the levels of cytotoxicity and inflammatory response were correlated with the intracellular concentration of VGCF. A relationship between the intracellular concentration of VGCF and cytotoxic effects was observed in both cell lines. The results indicate that dispersants affect VGCF uptake into cells and that cytotoxicity depends on the intracellular concentration of VGCF, not on the exposed dosage. Thus, toxicity appears to depend on exposure time, even at low VGCF concentrations, because VGCF is biopersistent.

We examined differences in cellular responses to multi-walled carbon nanotubes (MWCNTs) using malignant pleural mesothelioma cells (MESO-1), bronchial epithelial cells (BEAS-2B), neuroblastoma cells (IMR-32), and monoblastic cells (THP-1), before and after differentiation. MESO-1, BEAS-2B and differentiated THP-1 cells actively endocytosed MWCNTs, resulting in cytotoxicity with lysosomal injury. However, cytotoxicity did not occur in IMR-32 or undifferentiated THP-1 cells. Both differentiated and undifferentiated THP-1 cells exhibited an inflammatory response. Carbon blacks were endocytosed by the same cell types without lysosomal damage and caused cytokine secretion, but they did not cause cytotoxicity. These results indicate that the cytotoxicity of MWCNTs requires not only cellular uptake but also lysosomal injury. Furthermore, it seems that membrane permeability or cytokine secretion without cytotoxicity results from several active mechanisms. Clarification of the cellular recognition mechanism for MWCNTs is important for developing safer MWCNTs.

There is increasing interest in the unique biological and medical properties of carbon nanotubes (CNTs), and it is expected that biomaterials incorporating CNTs will be developed for clinical use. There has been a great deal of progress in improving the various properties of CNTs for use in biomaterials and for promotion of tissue regeneration as scaffold materials. The effects of CNTs on cells and tissues are extremely important for their use in biomaterials. This tutorial review clarifies the current state of knowledge in the interdisciplinary field of CNT-based nanobiotechnology to determine whether CNTs may be useful in biomaterials. Future perspectives in this rapidly developing field will also be discussed.

Carbon nanotubes (CNTs) have been used in various fields as composites with other substances or alone to develop highly functional materials. CNTs hold great interest with respect to biomaterials, particularly those to be positioned in contact with bone such as prostheses for arthroplasty, plates or screws for fracture fixation, drug delivery systems, and scaffolding for bone regeneration. Accordingly, bone-tissue compatibility of CNTs and CNT influence on bone formation are important issues, but the effects of CNTs on bone have not been delineated. Here, it is found that multi-walled CNTs adjoining bone induce little local inflammatory reaction, show high bone-tissue compatibility, permit bone repair, become integrated into new bone, and accelerate bone formation stimulated by recombinant human bone morphogenetic protein-2 (rhBMP-2). This study provides an initial investigational basis for CNTs in biomaterials that are used adjacent to bone, including uses to promote bone regeneration. These findings should encourage development of clinical treatment modalities involving CNTs.

Carbon nanotubes (CNTs) possess exceptional mechanical, thermal, and electrical properties, facilitating their use as reinforcements or additives in various materials to improve the properties of the materials. Furthermore, chemically modified CNTs can introduce novel functionalities. In the medical field, biomaterials are expected to be developed using CNTs for clinical use. Biomaterials often are placed adjacent to bone. The use of CNTs is anticipated in these biomaterials applied to bone mainly to improve their overall mechanical properties, for applications such as high-strength arthroplasty prostheses or fixation plates and screws that will not fail. In addition, CNTs are expected to be used as local drug delivery systems (DDS) and/or scaffolds to promote and guide bone tissue regeneration. However, studies examining the use of CNTs as biomaterials still are in the preliminary stages. In particular, the influence of CNTs on osteoblastic cells or bone tissue is extremely important for the use of CNTs in biomaterials placed in contact with bone, and some studies have explored this. This review paper clarifies the current state of knowledge in the context of the relationship between CNTs and bone to determine whether CNTs might perform in biomaterials in contact with bone, or as a DDS and/or scaffolding for bone regeneration.