Table 4.
Cytotoxicity evaluations in in vitro studies induced by CNC- and CNC-based materials.
| Material | Cellulose Source | Toxicological Experiment |
Cells Lines |
Toxicological Results | Results and Possible Application | Ref. |
|---|---|---|---|---|---|---|
| CNC | ||||||
| CNC | Cotton (Whatman 1 filter paper) | MTS assay; ATP assay. |
BEAS 2B hMDMs |
Cytotoxicity at 100 mg/mL; No micronuclei induction after exposure to 2.5–100 mg/mL; No induction of proinflammatory cytokines in hMDMs. |
Toxicity impact on lungs or bone marrow | [181] |
| CNC CNC- carboxyl groups |
Softwood cellulose pulp | MTS assay | CaCO-2, HeLa, MDCK, J774 |
CNC not exhibit any significant cytotoxicity; can exert stress on cells if they possess a high charge density; Charge-dependent decrease in mitochondrial activity (charge contents > 3.9 mmol/g). |
Drug delivery | [180] |
| c-CNCs t-CNCs |
Cotton Tunicate from Stuela clava |
LDH assay | A549 MDM MDDC |
The aspect ratio in combination with CNCs dose influences the uptake by the 3D co-culture system of the human epithelial airway barrier system. | Toxicity impact on lungs | [205] |
| CNC | Wood pulp | TB assay | A549 | CNC were nontoxic to A549 cells; CNC induced a robust inflammatory response; CNC particles induced a more robust inflammatory response compared to NCF. |
Comparable toxicity of CNC with CNF | [185] |
| CNCgel CNCdry |
Wood pulp | LDH assay | MH-S | Low conc. (1.5 and 5 μg/cm2) induce no cytotoxicity; A high dose of CNCdry induced a decrease in cell viability; CNC exposure further altered the secretion of cytokines. |
Toxicity impact on lungs | [182] |
| CNC | Wheat bran | MTT assay | Caco-2 | Dose-dependent decrease in cell viability, but only with significant results above 1000 μg/mL; The cell viability decreased significantly upon contact with CNC90 (88.09%) at 2000 μg/mL, although CNC30 (92.81%) and CNC60 (93.11%) did not significantly decrease the cell viability. |
Biocompatible nanocomposites | [197] |
| K-CNC R-CNC |
Rubberwood fiber Kenaf-bast fiber | MTT assay | RAW 264.7 HaCaT |
Cytotoxicity of K-CNC and R-CNC is not significant up to 700 μg/mL; K-CNC and R-CNC induced the formation of ROS in RAW264.7 macrophages. |
Biocompatible nanocomposites | [183] |
| CNC CNC-FL CNC-HM |
Cellulose pulp | MTT assay | ATCC PCS201012, A375 |
No cytotoxicity in direct and indirect contact assays. | Drug delivery |
[118] |
| CNC in nanocomposites | ||||||
| Collagen/CNCs/ GMs scaffolds |
MCC | MTT assay | HUVECs | No cytotoxicity; Excellent biocompatibility. |
Vascular TE | [133] |
| CNC CNC-AEM CNC-AEMA |
Softwood pulp | ATP assay |
J774 A.1 PBMNC |
One cationic CNC induced secretion of proinflammatory cytokine IL-1b associated with increase mitochondrial-derived ROS and extracellular ATP levels. | Drug and DNA delivery systems | [206] |
| PLA/CNCg-PEG nanocomposites | Southern pine |
Live/dead assays | hMSCs | Suitable biocompatibility; Nontoxic effect on hMSCs proliferation. |
Bone TE | [134] |
| TEMPO-CNC reinforced PVA hydrogels |
MCC | AB assay | HCE-2cells | Nontoxicity; Excellent biocompatibility; The HCE-2 cells viability above the 70%. |
Ophthalmic applications | [138] |
| PVA/CNC nanocomposites |
Sugarcane bagasse | MTT assay | L929 | Noncytotoxic effect; Strong attachment and proliferation of human fibroblast skin cells on the scaffold. |
TE scaffolds | [131] |
| GA-HA-CNC hydrogels |
MCC | CCK-8 assay | NIH-3T3 | Cell viability, at 1, 4, and 7 days, higher than 70% limit; No foreign body response. |
Skin TE | [132] |
| CS/Gel/NCC/CP nanocomposites |
Soft wood cellulose fibers |
MTT assay | Fibroblast cell | Lack of cytotoxicity after 3 days of increasing the cells’ viability. | Wound healing | [113] |
| CNC/PVA | MCC | AB assay | HCE-2 | Nontoxic and cytocompatible profile of the CNC-PVA hydrogel; Suitable biocompatibility toward HCE-2. |
Ophthalmic applications |
[207] |
Abbreviations: BEAS 2B—Human bronchial epithelial cells; hMDMs—Monocyte-derived macrophages; Caco-2—Human colon carcinoma cells; HeLa—Human cervix; MDCK—Dog kidney; J774—Mouse macrophages; A549—Epithelial cells; MDM—Human blood monocyte-derived macrophages; MDDC—Dendritic cells; MH-S—Murine alveolar macrophages; RAW 264.7—Macrophages; ATCC PCS201012—Primary human fibroblasts; A375—Malignant melanoma cells; J774A.1—Mouse monocyte/macrophage; PBMNC—Peripheral blood mononuclear cells; hMSCs—Human mesenchymal stem cells; L929—Mouse fibroblast; NIH-3T3—Fibroblast; HCE-2—Human corneal epithelial cells; LDH assay—Lactate dehydrogenase cytotoxicity assay; MTT assay—(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay; TB assay—Trypan blue exclusion staining cell viability assay; MTS assay—CellTiter-Glo luminescent cell viability assay; MCC—Microcrystalline cellulose.