Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose

Aimonen, Kukka; Suhonen, Satu; Hartikainen, Mira; Lopes, Viviana R.; Norppa, Hannu; Ferraz, Natalia; Catalán, Julia

doi:10.3390/nano11020389

Cited by 15 publications

(31 citation statements)

References 52 publications

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“…Similar results were obtained for modified cellulose nanofibrillation by Aimonen et al [ 57 ], who investigated whether wood-derived nanofibrillated cellulose (NFC) induces intracellular ROS production. Only U-NFC (unmodified) induced a significant increase in ROS formation compared to the negative control at 500 µg/mL after 24 h of exposure, whereas C-NFC (carboxymethylated), H-NFC (hydroxypropyltrimethylammonium), P-NFC (phosphorylated), and S-NFC (sulphoethylated) did not significantly increase the level of ROS for any doses or exposure times.…”

Section: Resultssupporting

confidence: 84%

Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films

Kędzierska

Blilid

Miłowska

et al. 2021

IJMS

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Marine polysaccharides are believed to be promising wound-dressing nanomaterials because of their biocompatibility, antibacterial and hemostatic activity, and ability to easily shape into transparent films, hydrogels, and porous foams that can provide a moist micro-environment and adsorb exudates. Current efforts are firmly focused on the preparation of novel polysaccharide-derived nanomaterials functionalized with chemical objects to meet the mechanical and biological requirements of ideal wound healing systems. In this contribution, we investigated the characteristics of six different cellulose-filled chitosan transparent films as potential factors that could help to accelerate wound healing. Both microcrystalline and nano-sized cellulose, as well as native and phosphorylated cellulose, were used as fillers to simultaneously elucidate the roles of size and functionalization. The assessment of their influences on hemostatic properties indicated that the tested nanocomposites shorten clotting times by affecting both the extrinsic and intrinsic pathways of the blood coagulation system. We also showed that all biocomposites have antioxidant capacity. Moreover, the cytotoxicity and genotoxicity of the materials against two cell lines, human BJ fibroblasts and human KERTr keratinocytes, was investigated. The nature of the cellulose used as a filler was found to influence their cytotoxicity at a relatively low level. Potential mechanisms of cytotoxicity were also investigated; only one (phosphorylated microcellulose-filled chitosan films) of the compounds tested produced reactive oxygen species (ROS) to a small extent, and some films reduced the level of ROS, probably due to their antioxidant properties. The transmembrane mitochondrial potential was very slightly lowered. These biocompatible films showed no genotoxicity, and very importantly for wound healing, most of them significantly accelerated migration of both fibroblasts and keratinocytes.

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Section: Resultssupporting

confidence: 84%

Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films

Kędzierska

Blilid

Miłowska

et al. 2021

IJMS

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“…This may partly be due to the broad range of CNF properties mainly arising from the fibre source, the extraction/production method, and the surface chemistry [ 8 ]. With the exception of a few studies assessing the toxicological potential of cellulose nanofibrils that only differ in their surface chemistry [ 34 – 36 ], most of the reported attempts to compare different CNF types have been challenged by the many variables affecting the results [ 20 – 22 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils

et al. 2022

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Background Cellulose nanofibrils (CNFs) have emerged as a sustainable and environmentally friendly option for a broad range of applications. The fibrous nature and high biopersistence of CNFs call for a thorough toxicity assessment, but it is presently unclear which physico-chemical properties could play a role in determining the potential toxic response to CNF. Here, we assessed whether surface composition and size could modulate the genotoxicity of CNFs in human bronchial epithelial BEAS-2B cells. We examined three size fractions (fine, medium and coarse) of four CNFs with different surface chemistry: unmodified (U-CNF) and functionalized with 2,2,6,6-tetramethyl-piperidin-1-oxyl (TEMPO) (T-CNF), carboxymethyl (C-CNF) and epoxypropyltrimethylammonium chloride (EPTMAC) (E-CNF). In addition, the source fibre was also evaluated as a non-nanosized material. Results The presence of the surface charged groups in the functionalized CNF samples resulted in higher amounts of individual nanofibrils and less aggregation compared with the U-CNF. T-CNF was the most homogenous, in agreement with its high surface group density. However, the colloidal stability of all the CNF samples dropped when dispersed in cell culture medium, especially in the case of T-CNF. CNF was internalized by a minority of BEAS-2B cells. No remarkable cytotoxic effects were induced by any of the cellulosic materials. All cellulosic materials, except the medium fraction of U-CNF, induced a dose-dependent intracellular formation of reactive oxygen species (ROS). The fine fraction of E-CNF, which induced DNA damage (measured by the comet assay) and chromosome damage (measured by the micronucleus assay), and the coarse fraction of C-CNF, which produced chromosome damage, also showed the most effective induction of ROS in their respective size fractions. Conclusions Surface chemistry and size modulate the in vitro intracellular ROS formation and the induction of genotoxic effects by fibrillated celluloses. One cationic (fine E-CNF) and one anionic (coarse C-CNF) CNF showed primary genotoxic effects, possibly partly through ROS generation. However, the conclusions cannot be generalized to all types of CNFs, as the synthesis process and the dispersion method used for testing affect their physico-chemical properties and, hence, their toxic effects.

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“…It was demonstrated that the metabolic activity of the cells was not significantly affected by the presence of the NFC materials (concentration range 500–50 μg/mL), and no signs of toxicity in terms of cell membrane damage were observed. In vitro toxicology of the same five CNFs-modified samples was also investigated by Aimonen et al [ 189 ] studied the same materials on human bronchial epithelial (BEAS-2B) cells, when observed that all NFCs samples, regardless of the surface functionalization with different surface charges, showed low cytotoxicity, which did not exceed 10%. Moreover, unmodified NFC (U-NFC) and carboxymethylated NFCs (C-NFC) were able to increase intracellular reactive oxygen species (ROS) formation.…”

Section: Toxicological Evaluation and Potential Limitations Of Ncs-based Materialsmentioning

confidence: 96%

“…Several studies evaluated the influence of surface charges of NCs materials on cytotoxicity effects when considered for medical applications [ 161 , 180 , 187 , 189 ]. CNC with different amounts of carboxyl groups have demonstrated a charge-dependent decrease in mitochondrial activity for higher charge content [ 180 ].…”

Section: Toxicological Evaluation and Potential Limitations Of Ncs-based Materialsmentioning

confidence: 99%

Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Nicu¹,

Ciolacu

Ciolacu³

2021

Pharmaceutics

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Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

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Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose

Cited by 15 publications

References 52 publications

Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films

Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films

Surface functionalization and size modulate the formation of reactive oxygen species and genotoxic effects of cellulose nanofibrils

Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

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