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

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: 80–170 × 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