In Vitro Toxicity Evaluation of Lignin-(Un)coated Cellulose Based Nanomaterials on Human A549 and THP-1 Cells

Abstract

A significant amount of research toward commercial development of cellulose based nanomaterials (CNM) is now in progress with some potential applications. Using human A549 and THP-1 cells, we evaluated the biological responses of various CNMs, made out of similar material but with functional and morphological variations. While A549 cells displayed minimal or no cytotoxic responses following exposure to CNMs, THP-1 cells were more susceptible to cytotoxicity, cellular damage and inflammatory responses. Further analysis of these biological responses evaluated using hierarchical clustering approaches was effective in discriminating (dis)-similarities of various CNMs studied and identified potential inflammatory factors contributing to cytotoxicity. No correlation between cytotoxicity and surface properties of CNMs was found. This study clearly highlights that, in addition to the source and characteristics of CNMs, cell type-specific differences in the recognition/uptake of CNMs along with their inherent capability to respond to external stimuli are crucial for assessing the toxicity of CNMs.

The Crystallinity and Aspect Ratio of Cellulose Nanomaterials Determine Their Pro‐Inflammatory and Immune Adjuvant Effects In Vitro and In Vivo

“…While currently there are no published data revealing a safety concern for nanocellulose in the workplace or in consumer products, experimental evidence has been collected for the potential hazardous effects of CNCs and CNFs . While most cellular studies have addressed cytotoxicity, inflammation and genotoxicity, which can be related to differences in the cellular uptake of CNCs versus CNFs or their ability to generate oxidative stress, most in vivo studies have focused on the effects in the lung and the reproductive system . For instance, pulmonary exposure to CNCs is capable of generating dose‐dependent pro‐inflammatory effects and oxidative stress, while CNFs are capable of inducing TH1 polarizing effects in the lung .…”

“…Cullen et al have observed dose‐dependent recruitment of inflammatory cells to the peritoneal cavity of mice exposed to CNFs, while Yanamala et al have shown that oropharyngeal aspiration of CNCs in mice can generate oxidative stress, cytotoxicity, and pro‐inflammatory effects . Moreover, while comparing CNFs to CNCs in transformed human lung epithelial cells, CNFs were shown to generate more cytotoxicity than CNCs, but the reverse was true for the pro‐inflammatory effects of these materials . However, other than comparative studies of the biological impact of cellulose nanocrystals versus nanofibrils, relatively few studies have attempted to explain the biological effects and hazard potential of nanocellulose in terms of aspect ratio, crystallinity and surface reactivity, physicochemical characteristics that have been shown to be of importance the adverse health effects of HAR material such as carbon nanotubes (CNTs), CeO 2 nanorods, TiO 2 nanobelts, and AlOOH nanorods, etc …”

Three-Dimensional Printing of Wood-Derived Biopolymers: A Review Focused on Biomedical Applications

“… 145 Thus, lignin, with its hydrophobic character, could be incorporated into hydrogels to tune the hydrophilicity of the resulting matrix. 146 , 147 Another emerging area of application is the development of lignin-based nanoparticles as nanocarriers for drug delivery. 68 , 148 Stable lignin-based nanosystems may offer promising nanodelivery solutions for medical applications when hydrogel inks are developed for printing.…”

Risk Analysis of Cellulose Nanomaterials by Inhalation: Current State of Science

“…To date, twelve studies from 2011–2018 have been published on the short-term inhalation toxicity of CNs [12,13,14,15,16,17,18,19,20,21,22,23]. These studies use both cellular (in vitro) [16,17,18,19,20,21] and animal (in vivo) [12,13,14,15,16,22,23] models to investigate the effect of CNC and CNF exposure on the lung. The main findings from these studies are summarized here before analyzing the studies using two published approaches for their usefulness for risk assessment purposes.…”

“…In a study using monocultures, Yanamala et al (2016) exposed aqueous suspensions of different forms of CNC and CNF (5 μg/mL–300 μg/mL) to a human lung epithelial cell line (A549) or a human monocytic (immune) cell line (THP-1) for 24 or 72 h [19]. Bulk microcrystalline cellulose (MCC) was used as a reference material.…”