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Table 1 Succinct overview of the key findings regarding the biological impact of nanocellullose samples studied within the literature

From: A critical review of the current knowledge regarding the biological impact of nanocellulose

First author Year Ref Nano-cellulose type Dimensions Test system Cytotoxicity Inflammatory response Oxidative stress Genotoxicity Main conclusions from study
Moreira 2009 [82] BC 50–1500 × 3–5 nm 3T3 fibroblasts, Chinese Hamster ovary cells n/a n/a Benign material, beware of material modifications
Kovacs 2010 [76] NCC 200 × 10 × 5 nm Rainbow trout, Daphnia magna, Ceriodaphnia dubia, Fathead minnow, Vibrio fischeri, Pseudokirchneriella subcapitata, Hydra attenuate, Danio rerio, Rainbow trout hepatocyte cells n/a n/a Low toxicity potential and low environmental risk
Jeong 2010 [81] BC n/a Human umbilical vein epithelial cells; C57/Bl6 mouse model n/a n/a n/a Suitability for tissue engineering
Mahmoud 2010 [83] CNC 130–200 × 10–20 nm Human embryonic kidney cells (HEK 293) and Spodoptera frugiperda Ovary cells (Sf9) + n/a n/a n/a Surface charge influences toxicity and uptake
Clift 2011 [91] CNC 220 ± 6.7 × 15 ± 5 nm 3D Co-culture (A549 epithelial cells, combined with human blood monocyte derived macrophages (MDM) and dendritic cells (MDDC)) + n/a n/a Length, stiffness and possibly origin affect CNC-cell interactions
Male 2012 [77] NCC 120–140 × 3–6 nm Chinese Hamster lung cells (V79) and Spodoptera frugiperda ovary cells (Sf9) n/a n/a n/a Origin/extraction, treatment and carboxylic acid content influence toxicity
Dong 2012 [78] CNC 181 ± 9 × 5.0 ± 0.2 nm Human brain microvascular endothelial cells (HBMEC), mouse endothelial brain cells (bEnd.3), RAW 264.7 macrophages, human breast epithelial cells (MCF-10A,MDA-MB-231 and MDA-MB-468), human hepatocyte cells (KB), prostate cancer cells (PC-3), Rat brain fibroblasts (C6) n/a n/a n/a Low unspecific uptake, no cytotoxicity appropriate for biomedical applications
de Lima 2012 [87] CNF White: 135 ± 50 × 14 ± 4 nm,
Brown: 140 ± 45 × 11 ± 3 nm,
Green: 180 ± 45 × 13 ± 2 nm,
Ruby: 130 ± 25 × 10 ± 4 nm
Curaua: 80170 × 6–10 nm
Allium cepa, 3T3 fibroblasts, and lymphocytes + n/a n/a + Genotoxicity depends on cell type and color used
Hannukainen 2012 [93] NFC n/a BEAS 2B epithelial cells n/a + Elucidation of limited genotoxicity
Pereira 2013 [88] CNF 85–225 µm × 6–18 nm Bovine fibroblasts + n/a + n/a High dose of CNF exposure leads to negative cell effects
Pereira 2014 [84] CNF 85–225 µm × 6–18 nm Chlorella vulgaris + n/a + n/a CNF exposure can affect algal viability and growth
Endes 2014 [80] CNC Cotton: 170 ± 72 × 19 ± 7 nm
Tunicate: 2.3 ± 1.4 µm × 31 ± 7 nm
3D Co-culture [A549 epithelial cells, combined with human blood monocyte derived macrophages (MDM) and dendritic cells (MDDC)] n/a Benign nature of CNCs, independent of their dimensions
Hanif 2014 [86] CNC 256 ± 64.8 nm
140.5 ± 37.5 nm
108.4 ± 94.8 nm
1174 ± 338.7 nm
3T3 fibroblasts and human colon epithelial cells (HCT116) +
+
n/a n/a n/a Cytotoxicity observed for concentrations below 250 µg/mL, dimensions irrelevant
Catalan 2014 [85] CNC 135 ± 5 × 7.3 ± 0.2 nm BEAS 2B epithelial cells and human blood monocyte derived macrophages   n/a 55% cytotoxicity mainly ≥100 µg/mL
Yanamala 2014 [90] CNC 90.19 ± 3.03 nm
207.9 ± 49 nm
n/a
C57BL/6 mouse model + + + n/a Nanocellulose dimensions rather than the source exert a strong influence on the biological response
Stefaniak 2014 [68] CNC, CNF ~105 × 10 nm, ~165 × 11 nm RAW 264.7 macrophages n/a n/a Cell free + in vitro – n/a High biodurability
Endes 2015 [79] CNC Cotton: 237 ± 118 × 29 ± 13 nm
Tunicate: 2244 ± 1687 × 30 ± 8 nm
3D Co-culture [A549 epithelial cells, combined with human blood monocyte derived macrophages (MDM) and dendritic cells (MDDC)] @ Air–Liquid Interface n/a n/a n/a Length and concentration have a significant effect on CNC-cell interactions
Colic 2015 [89] CNF 33 ± 2.5 µm × 10–70 nm Mouse fibroblasts (L929), thymocytes, and peripheral blood mononuclear cells (PBMCs) + + n/a High concentration leads to observed effects
Shvedova 2016 [94] CNC 158 ± 97 nm × 54 ± 17 nm C57BL/6 mouse model + + + + Male mice exhibit significantly higher adverse pulmonary effects compared to female mice (gender differences)
Farcas 2016 [95] CNC 158 ± 97 nm × 54 ± 17 nm Cauda epididymal sperm samples + + + + Pulmonary exposure of CNC affects male mice reproduction system
  1. These are structured, as referred to in the main text, as to the main biochemical endpoints studied within the field, including, Cytotoxicity, Inflammatory Response, Oxidative Stress and Genotoxicity. For each endpoint, +  response was observed and –  no response observed; n/a  not investigated). The final column highlights a brief, considered statement of the outcome of the referenced study. Studies are presented in the chronological order that they were published into the public domain