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Particle and Fibre Toxicology

, 14:1

First Online: 10 January 2017Received: 07 July 2016Accepted: 15 December 2016DOI: 10.1186-s12989-016-0182-0

Cite this article as: Lopes, V.R., Sanchez-Martinez, C., Strømme, M. et al. Part Fibre Toxicol 2017 14: 1. doi:10.1186-s12989-016-0182-0


BackgroundNanocellulose, and particularly nanofibrillated cellulose NFC, has been proposed for a diversity of applications in industry and in the biomedical field. Its unique physicochemical and structural features distinguish nanocellulose from traditional materials and enable its use as an advance nanomaterial. However, its nanoscale features may induce unknown biological responses. Limited studies with NFC are available and the biological impacts of its use have not been thoroughly explored. This study assesses the in vitro biological responses elicited by wood-derived NFC gels, when human dermal fibroblasts, lung MRC-5 cells and THP-1 macrophage cells are exposed to the nanomaterial. Furthermore, whether the presence of surface charged groups i.e. carboxymethyl and hydroxypropyltrimethylammonium groups on NFC can induce distinct biological responses is investigated.

ResultsThe introduction of surface charged groups resulted in individual nanofibrils, while fibril aggregates predominated in the unmodified NFC gel suspensions as observed by transmission electron microscopy. In the presence of proteins, the surface modified NFCs formed compact agglomerates while the agglomeration pattern of the unmodified NFC was similar in the presence of proteins and in physiological buffer. Unmodified and modified NFC gels did not induce cytotoxicity in human dermal fibroblasts, lung and macrophage cells. No significant ROS production by THP-1 macrophages was found and no cellular uptake was observed. However, an inflammatory response was detected when THP-1 macrophages were treated with unmodified NFC as assessed by an increase in TNF-α and IL1-β levels, an effect that was absent when surface charged groups were introduced into NFC.

ConclusionsTaken together, the data presented here show the absence of cytotoxic effects associated with the exposure to unmodified, carboxymethylated and hydroxypropyltrimethylammonium-modified NFCs. Unmodified NFC presented a pro-inflammatory effect which can be further moderated by introducing surface modifications such as carboxymethyl and hydroxypropyltrimethylammonium groups into the nanofibrils. The present findings suggest that the inflammatory response to NFC might be driven by the material surface chemistry, and thus open up for the possibility of designing safe nanocellulose materials.

KeywordsCytotoxicity Inflammation Nanocellulose Surface chemistry AbbreviationsABAlamar blue

A-NFCAnionic nanofibrillated cellulose

ANOVAAnalysis of variance

C-NFCCationic nanofibrillated cellulose


DCFH-DADichlorodihydrofluorescein diacetate

DMEM-F12Dulbecco’s Modified Eagle Medium: Nutrient Mixture F-12

DMSODimethyl sulfoxide

ECACCEuropean Collection of Authenticated Cell Cultures

IL1-βInterleukin 1 beta

LDHLactate Dehydrogenase


NFCNanofibrillated cellulose

PBSPhosphate buffer

PMAPhorbol myristate acetate

PMBPolymyxin B

ROSReactive oxygen species

RPMI 1640Roswell Park Memorial Institute RPMI 1640 Medium

SEMStandard error of the mean

TBHPTert-butyl hydroperoxide

TEMTransmission electron microscopy

TNF-αTumor necrosis factor α

U-NFCUnmodified cellulose nanofibrillated

Electronic supplementary materialThe online version of this article doi:10.1186-s12989-016-0182-0 contains supplementary material, which is available to authorized users.

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Autor: Viviana R. Lopes - Carla Sanchez-Martinez - Maria Strømme - Natalia Ferraz


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