Biomedical Application of Nanocellulose Composites
In consideration of biocompatibility and the remarkable reinforcement effect of nanocellulose in composite applications, numerous studies related to various biomedical applications have been conducted. Generally, biomedical or biomaterial application can be classified into several categories including for uses in pharmaceutical field (i.e., drug deliveries), general surgeries (i.e., sutures, burn dressings, and skin substitutes), cardiovascular medical devices (i.e., stents, grafts), dental and orthopedic applications (i.e., implants, scaffolds), ophthalmologic applications (i.e., contact lenses, prosthetic retina), and bioelectrodes or biosensors. Several studies on nanocellulose for biomedical application have been reviewed elsewhere (Abdul Khalil et al., 2015; Abitbol et ah, 2016; Jorfi & Foster, 2015; Sharip & Ariffin, 2019).
Nontoxic, biodegradable and biocompatible, cellulose-based hydrogels are highly hydrated porous cellulosic soft materials with good thermal and mechanical properties. These nanocellulose-based gels can be processed from plant or bacterial cellulose, which are nontoxic, highly hydrated porous soft, biocompatible, biodegradable, hydrophilic, and renewable. Nanocellulose, whether CNC, CNF, or BNC, has abundant hydroxyl groups, high surface area, large specific surface area, high crystallinity, high strength and stiffness, low' weight, biodegradability, high aspect ratio, great mechanical properties and thermal resistance, and it can be chemically modified with functional groups or by grafting biomolecules. According to Curvello et al. (2019), there are five main categories of nanocellulose hydrogel applications: 3D cell culture, tissue engineering, drug delivery, diagnostics, and separation of biomolecules (Figure 8.4). Herein, recent findings on nanocellulose composites for biomedical application are highlighted.
Pharmaceutical
An important aspect related to drug delivery systems to the target treatment site is a controlled release of the drug or biological agent (Rezaie et al., 2015). A regulated controlled system is essential to ensure the release of the right dosage at the right time and to prevent the early release of the drug prior to reaching the target site. The use of coating on the drug-embedded matrix or carrier and a hydrophilic matrix has been addressed as one of the popular approaches in developing extended-release dosage forms attributed to its flexible and well-designed structure allowing a reproducible release profile (Abdul Khalil et al., 2015).
For instance, the release of 5-fluoracil (5-FU), a drug for cancer treatment, was found controllable in polymer-modified CNF cryogel microspheres. The CNF acts as a microreactor possessing a robust and highly porous framework, enabling good stability of the temperature-sensitive monomer, N-isopropylacrylamide (NIPAm), thus resulting in a controllable drug release system that is dependent on temperature
FIGURE 8.4 Nanocellulose hydrogel is biocompatible, biodegradable, and shows potential for multiple biomedical applications. (Reproduced with permission from Curvello et a!., 2019.)
changes (Zhang et al„ 2016). Another study reported the uses of nanocellulose composite hydrogels for regulating drug releases through temperature and pH changes. Addition of poly-NIPAm with alterations of carboxyl charge level of the CNF during 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)-mediated oxidation resulted in dual-responsive behavior of drug releases, suggesting promising use of CNF-poly(NIPAm) composite hydrogels for drug delivery systems (Masruchin et al.. 2018). A more recent study was conducted using CNF and TEMPO-mediated oxidized CNF with polyvinyl alcohol (PVA) for investigating the releases of acetaminophen. The alternated amorphous and crystalline structure of CNF in PVA aids in the entanglement of the drug in the matrix, hence enabling a controlled released of acetaminophen by over 144 hours (O'Donnell et al., 2020).
A study conducted by Muller et al. (2013) on the applicability of BNC as a drug delivery system for proteins, using serum albumin as a model drug, showed that the BNC is proven to be non-cytotoxic as well as environment friendly with an excellent biocompatibility (Figure 8.5). This was focused on proteins as they are introduced into the market as an increasing part of pharmaceutical compounds. In addition, there is a growing interest for BNC as additives in medical devices; for example, in growth factors, cell attractants for tissue engineering, or antibodies for wound healing.
Moreover, in order to identify the usage of novel materials in drug delivery applications, Mohd Amin et al. (2012) investigated the use of bacterial cellulose (BC) incorporated with different proportions of acrylic acid (AA) to produce hydrogels
FIGURE 8.5 Visualization of bovine serum albumin (BSA) distribution in bacterial nanocellulose (BNC) (cross sections) by staining with BCA assay reagent. BNC loaded by adsorption (a) and high-speed technique (b). corresponding unloaded controls incubated only in buffer without BSA (adsorption, c; vortex treatment, d). and untreated, unstained BNC (e and f) (scale bars, 5 mm). (Reproduced with permission from Muller et al.. 2013.)
by exposure to accelerated electron-beam irradiation at different doses. The result revealed that the morphology of the hydrogels is much dependent on the irradiation dose and composition of hydrogel. These morphological observations propose that the highly porous sponge-like structure of BC/AA hydrogels helps water diffusion in all directions, thus making these hydrogels suitable for drug release systems for protein-based drugs (Figure 8.6). The pore sizes of the 208035 (60-190 pm), 208050 (20-110 pm), and 307035 (2-50 pm) hydrogels recommend that they are more suitable compared to the other hydrogels for bovine serum albumin (BSA) loading.
