Assessing cytotoxicity and biocompatibility of cellulose nanofibrils on alveolar macrophages

Cellulose nanofibrils (CNFs) are a promising new material derived from biomass, known for their lightweight, high strength, and low thermal expansion properties. However, concerns have been raised about their potential health impact due to their fibrous and ultrafine nature. This study aimed to evaluate the effects of different types of CNFs on rat alveolar macrophages (NR8383). The CNFs tested included TEMPO-oxidized CNFs (CNF1), phosphorylated CNFs (CNF2), mechanically fibrillated CNFs from softwood bleached kraft pulp (CNF3), CNFs derived from citrus peels (CNF4), and two size fractions (coarse and ultrafine) of softwood bleached kraft pulp obtained by aqueous counter collision processing (CNF5 and CNF6). The findings showed no significant production of reactive oxygen species in any of the CNF exposure groups. However, exposure to CNF1, CNF2, and CNF3 led to increased mitochondrial dehydrogenase activity, elevated pro-inflammatory cytokine production, and upregulation of inflammation-related genes. These effects were less pronounced in the CNF4, CNF5, and CNF6 groups. Cellular uptake of CNFs was observed across all groups, and the response to CNF exposure differed from the response to microcrystalline cellulose, which was used as a reference material. No clear correlation was found between the observed effects and the presence of biological contaminants, such as bacteria and endotoxins, in the CNF dispersions. These findings suggest that CNFs may either activate macrophages or demonstrate biocompatibility rather than cytotoxicity. The impact and biocompatibility of CNFs on alveolar macrophages appear to be influenced by various factors, including the source of the CNF raw material, the manufacturing process, physicochemical properties, and biological characteristics of the CNF dispersion. This study provides valuable insights into the potential inhalation effects of CNFs.