*4.3. Biomedical Application of Nanocellulose*/*CNT Composites*

Biomedical applications of composites of cellulose and CNTs are summarized in Table 1. These composites are important systems for drug delivery. The CNTs in the composites can be conjugated with many therapeutics, usually anticancer drugs, but also other types of drugs. For example, an osmotic pump tablet system coated with cellulose acetate membrane containing MWCNTs was developed for delivery of indomethacin (for a review, see [16,65]). Cancer cells can be killed by nanocellulose-CNT dispersions even without the presence of anticancer drugs. For example, nonmercerized type-II cellulose nanocrystals in dispersions with SWCNTs displayed cytotoxicity for human epithelial colorectal adenocarcinoma Caco-2 cells, but they enhanced the mitochondrial metabolism of normal cells [149].

Construction of sensors and biosensors is another important application of nanocellulose/CNT composites useful for (bio) technology and medicine. A tactile piezoresistance and thermoelectric-based sensor, mentioned above, which is capable of simultaneously sensing temperature and pressure, is fabricated from TEMPO-oxidized cellulose, PEDOT:PSS, AgNPs and CNTs [103]. Another pressure sensor was developed using aerogels consisting of plant cellulose nanofibers and functionalized few-walled CNTs [17]. Highly conductive and flexible membranes with a semi-interpenetrating network structure, fabricated from MWCNTs and cellulose nanofibers, showed the electrical features of capacitive pressure sensors and were promising for various electronics applications, e.g., touch screens [150]. Advanced flexible strain sensors for controlling the human body motion were fabricated by pumping hybrid fillers consisting of CNTs/CNCs into porous electrospun thermoplastic polyurethane membranes [91]. Other strain sensors were fabricated by a facile latex assembly approach, in which CNCs played a key role in tailoring the percolating network of conductive natural rubber/CNT composites [114]. A water-responsive shape memory hybrid polymer, based on a thermoplastic polyurethane matrix crosslinked with hydroxyethyl cotton cellulose nanofibers and MWCNTs, was also developed for constructing a strain sensor [90]. A flexible and highly sensitive humidity sensor, capable of monitoring human breath, was based on TEMPO-oxidized nanofibrillated cellulose and CNTs [104]. An electrochemical biosensor for three adenosine triphosphate (ATP) metabolites, namely uric acid, xanthine and hypoxanthine, was based on a composite of NH2-MWCNT/black phosphorene/AgNPs, dispersed in carboxymethyl cellulose [102]. Another electrochemical molecularly-imprinted sensor was based on a nanofibrous membrane prepared by the electrospinning technique from cellulose acetate, MWCNTs and polyvinylpyrrolidone, and was used for determining ascorbic acid [151]. An oxygen biosensor powered by a biofuel cell containing MWNCTs, a nanocellulose/polypyrrole composite, laccase and fructose dehydrogenase, was mentioned above [84]. Versatile wearable textile sensors, e.g., for gas sensing, were produced from cellulose nanofibers extracted from tunicates, homogeneously composited with SWCNTs, by wet spinning in an aligned direction [60].

Other important biomedical applications of nanocellulose/CNT composites are in electrical stimulation of cells and tissues in order to improve their regeneration and function, and in tissue engineering. For example, stretchable, flexible and electrically conductive biopatches for restorating conduction in damaged cardiac regions and for preventing arrhythmias were prepared. These patches were based on nanofibrillated cellulose/SWCNT ink three-dimensionally printed onto bacterial nanocellulose. They restored cardiac conduction after its disruption by a surgical incision made in the ventricular part of the heart in experimental dogs [52]. For neural tissue stimulation, multiblock conductive nerve scaffolds with self-powered electrical stimulation were prepared. These scaffolds were based on polypyrrole/bacterial nanocellulose composites with platinum nanoparticles on the anode side for glucose oxidation, and nitrogen-doped CNTs on the cathode side for oxygen reduction. These scaffolds enhanced the elongation of neurites outgrowing from rat dorsal root ganglions in vitro and stimulated nerve regeneration in a rat sciatic nerve gap model in vivo in comparison with composites containing only polypyrrole and bacterial nanocellulose. These scaffolds could replace the metal needles that are currently used for external electrical stimulation of neural tissue, which may cause pain and a risk of infection [106]. 3D printing was also used for creating scaffolds based on a conductive ink composed of wood-derived CNFs and SWCNTs. These scaffolds were intended for neural tissue engineering for experimental brain studies, and supported the attachment, growth and viability of human neuroblastoma SH-SHY5Y cells [51]. Other scaffolds for tissue engineering consisted of electrospun cellulose acetate nanofibers, assembled with positively-charged chitosan and negatively-charged MWCNTs via an LbL technique. These scaffolds promoted the adsorption of cell adhesion-mediating molecules from the serum supplement of the culture medium and the adhesion and growth of mouse subcutaneous L929 fibroblasts [117]. Our own results related to the potential application of nanocellulose/CNT composites as scaffolds for tissue engineering are reported in Appendix A.
