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Cytocompatibility and immunomodulatory properties of wood based nanofibrillated cellulose

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Abstract

Cellulose nanofibrils (CNFs), unique and promising natural materials have gained significant attention recently for biomedical applications, due to their special biomechanical characteristics, surface chemistry, good biocompatibility and low toxicity. However, their long bio-persistence in the organism may provoke immune reactions and this aspect of CNFs has not been studied to date. Therefore, the aim of this work was to examine and compare the cytocompatibility and immunomodulatory properties of CNFs in vitro. CNFs (diameters of 10–70 nm; lengths of a few microns) were prepared from Norway spruce (Picea abies) by mechanical fibrillation and high pressure homogenisation. L929 cells, rat thymocytes or human peripheral blood mononuclear cells (PBMNCs) were cultivated with CNFs. None of the six concentrations of CNFs (31.25 µg/ml–1 mg/ml) induced cytotoxicity and oxidative stress in the L929 cells, nor induced necrosis and apoptosis of thymocytes and PBMNCs. Higher concentrations (250 µg/ml–1 mg/ml) slightly inhibited the metabolic activities of the L929 cells as a consequence of inhibited proliferation. The same concentrations of CNFs suppressed the proliferation of PBMNCs to phytohemaglutinine, a T-cell mitogen, and the process was followed by down-regulation of interleukin-2 (IL-2) and interferon-γ production. The highest concentration of CNFs inhibited IL-17A, but increased IL-10 and IL-6 production. The secretion of pro-inflammatory cytokines, IL-1β and tumor necrosis factor-α as well as Th2 cytokine (IL-4), remained unaltered. In conclusion, the results suggest that these CNFs are cytocompatible nanomaterial, according to current ISO criteria, with non-inflammatory and non-immunogenic properties. Higher concentrations seem to be tolerogenic to the immune system, a characteristic very desirable for implantable biomaterials.

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Acknowledgments

This work was supported by the project MNT-Era-Net n-POSSCOG (Slovenian Ministry of Education, Science, Culture and Sport), and the project ON175102 (Ministry of Education, Science and Technological Development of R. Serbia). The authors thank Sergej Tomic, Jelena Djokic and Milan Markovic for technical support.

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Authors and Affiliations

  1. Medical Faculty of the Military Medical Academy, University of Defense in Belgrade, Crnotravska 17, 11002, Belgrade, Serbia

    Miodrag Čolić & Dušan Mihajlović

  2. Medical Faculty, University of Niš, Niš, Serbia

    Miodrag Čolić

  3. Division of Materials Science, Luleå University of Technology, 97187, Luleå, Sweden

    Aji Mathew & Narges Naseri

  4. Faculty of Mechanical Engineering, Institute for Engineering Materials and Design, University of Maribor, Maribor, Slovenia

    Vanja Kokol

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  1. Miodrag Čolić
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Correspondence to Miodrag Čolić.

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Čolić, M., Mihajlović, D., Mathew, A. et al. Cytocompatibility and immunomodulatory properties of wood based nanofibrillated cellulose. Cellulose 22, 763–778 (2015). https://doi.org/10.1007/s10570-014-0524-8

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  • DOI: https://doi.org/10.1007/s10570-014-0524-8

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