Biocompatibility and Toxicology of Nanocellulose Composites

The exploration of nanocellulose for biomedical applications is gaining attention mainly due to its favorable properties particularly its biocompatibility and low toxicology toward living cells. A search was done on lens.org using the keyword “nanocellulose biocompatibility” and it was found that the number of manuscripts focusing on the biocompatibility of nanocellulose has been increasing for years, as shown in Figure 8.2. Nevertheless, a similar search using another keyword “nanocellulose toxicology” showed an inconsistent trend of toxicology studies on nanocellulose, especially after 2015, as shown in Figure 8.3. This is worrisome as the toxicology properties of a material are one of the important factors that need to be considered for the development of safe biomedical applications.

Biocompatibility, in general, refers to the ability of an implanted material to perform its desired function without causing undesirable or systemic effects to the host (Afrin & Karim. 2015). In general, biocompatibility properties of materials for medical applications are widely tested either using in vitro or in vivo methods (Ferraz et al., 2012). According to Afrin and Karim (2015), the in vitro test is usually conducted at the initial stage to identify the host’s responses toward the implanted

A chart of published manuscripts focused on nanocellulose compatibility

FIGURE 8.2 A chart of published manuscripts focused on nanocellulose compatibility.

material under controlled conditions. Nevertheless, the true responses may not be reflected, and hence, in vivo testing is required at later stages.

For biomedical polymeric-based composites, many factors can influence their biocompatibility such as copolymer ratio, chemical structure and functional groups of the polymer, as well as morphologies and processing of fillers (Kulkarni & Rao, 2013). All these factors may influence the cellular activity of the targeted host.

In terms of cellulose, it cannot be degraded by the human body because it lacks cellulolytic enzymes; this may lead to some incompatibility (Lin & Dufresne, 2014). A similar effect is expected for nanocellulose.

Due to this issue, Zhang et al. (2019) tried to surface modify nanocellulose, particularly CNF, to improve its biocompatibility. The findings showed that crosslinking of CNF with adipic acid dihydrazide (ADH) and oxidized konjac glucomannan (OKGM) was able to improve the biocompatibility of CNF. It was reported that the cell viability kept was around 90% at all tested concentrations (1.25-5 mg/mL) for OKGM-ADH CNF, suggesting good biocompatibility of these materials. In fact, it was found that the OKGM-ADH CNF was able to support the growth of cells on the membrane surface. The cells survived, attached, and proliferated on the membrane.

In addition to biocompatibility, the toxicology properties of an implanted material need to be determined, to ensure it does not chemically interfere with the body system. Fundamentally, the main concept of toxicology is the “dose-response” relationship (Bourgeois et al., 2016). The severity of the toxic effect is related to the dose/ amount of substance that enters the body. In terms of nanocellulose, its toxicology properties have not been widely studied and, in fact, it has yet to be accepted as a safe implanted material in living organisms, especially humans. Thus, investigating CNF toxicology for biomedical applications is of great importance.

Recently, Deloid et al. (2019) studied the toxicology of CNF when it is consumed by rats. In vivo toxicity was evaluated in rats gavaged twice weekly for 5 weeks with 1% w/w suspensions of CNF. The findings revealed that CNF is nontoxic and nonhazardous when ingested in small quantities. Other than the study by Deloid et al. (2019), Table 8.3 summarized the toxicology reports involving nanocellulose.

TABLE 8.3

Examples of the Toxicological Evaluation of Nanocellulose-Based Materials for Biomedical Applications

Nanocellulose Type

Toxicological Experiment

Findings

Cellulose nanofiber (CNF)

In vitro cytotoxicity test of CNFs with fibroblast 3T3 cells.

The CNFs did not exert toxic behavior on fibroblast cells and showed no effect on the cell membrane, mitochondrial activity, or DNA proliferation.

Cellulose nanocrystals (CNC)

In vitro cytotoxicity evaluation of CNCs with nine different cell lines.

No cytotoxic effects in the concentration range (0-50 pg/mL) and with an exposure time of 48 hours.

Bacterial nanocellulose (BNC)

In vitro and in vivo cytotoxicity of BNC in human umbilical vein endothelial cells (with viability and flow cytometric assays) and mouse model.

No toxicity in endothelial cells and no biochemical differences were observed after 7 days in animal experiments.

Source: Adapted from Jorfi and Foster (2015).

All in all, most of the reports suggested that nanocellulose is safe and does not cause damage at the cellular and genetic levels.

 
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