In vitro biological responses to nanofibrillated cellulose by human dermal, lung and immune cells: surface chemistry aspect

Abstract

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

Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels

“…This hydrogel is easy to handle and is biocompatible with human cells, whilst also allowing the simple retrieval of cells from the scaffold for further use [25,26]. Although the immunogenicity of plant-derived NFC is still under investigation, the low immune response to other plant derived hydrogels has been reported [27] [12,28].…”

Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice

“…Compared to CNC, the NCF used in this study has been found to be more cytotoxic to human A549 cells (24 or 72 h post exposure) (Menas et al 2017) and in mice (24 h post-exposure) (Yanamala et al 2014). Other studies of different NCF types reported low cytotoxicity but robust inflammatory cytokine/chemokine production in dermal fibroblasts, lung MRC-5 cells, and THP-1 macrophages (Bhattacharya et al 2017;Lopes et al 2017). The present data indicate that by Day 14, NCF-treated mice exhibited an immune microenvironment favoring differentiation of T-cells toward a T H 1-phenotype (more obviously seen in highdose exposure group), as revealed by increased APC activation, maturation, and enhanced secretion of IL-12p70, MCP-1, MIP-1a, and GM-CSF (Colantonio et al 2002;Zhang et al 2014).…”

“…Fiber toxicity is driven by high aspect ratio with high strength and long retention times, and there is always concern for the induction of ASB-like pathogenicity for each emerging material or application. In the case of nanoscale fibers, additional variables are added that might complicate the established pathogenicity mechanisms due to uncertain biological fate and biocompatibility (Allegri et al 2016;Lopes et al 2017). The goal of the current study was to determine whether fibrillary nanocellulose, despite having the same chemical composition as the crystalline form, elicits different local and systemic subacute immune responses upon pulmonary exposure in a mouse model of bolus pharyngeal aspiration, and second, if the response would be closer to the one produced by micro-sized crocidolite fibers or CNTs.…”

Nanocellulose in Biotechnology and Medicine: Focus on Skin Tissue Engineering and Wound Healing

“…by functionalizing it with specific chemical groups or by endowing it with an electrical charge. Wood-derived nanofibrillated cellulose (NFC) modified with carboxymethyl and hydroxypropyltrimethylammonium groups elicited a lower pro-inflammatory effect than unmodified NFC in human dermal fibroblasts, in lung MRC-5 cells and in human macrophage-like THP-1 cells [273]. Anionic NFC films significantly activated THP-1 cells towards a pro-inflammatory phenotype, whereas cationic and unmodified cellulose induced only mild activation of these cells [274].…”