## 5 Cellulose-Based Biomaterials in Wound-Healing Augmentation
### CA-Based Hydrogels  
Hydrogel nanocomposites are high potent biomaterials for biomedical applications. Their mechanical strength, controlled drug release ability, stimuli-responsive behavior, biological interactions, and high elasticity encourage researchers to incorporate various nanoparticles in hydrogel networks. There are two methods for incorporating nanoparticles into a matrix hydrogel: one is to mix monomers' solutions and then produce the polymers, and the other one is to mix the produced polymers after the polymerization process. CA is a polymer that forms a biocompatible hydrogel. [PERSON] et al. [50] fabricated semi-interpenetrating polymer network (IPN) films based on CA and crosslinked poly(acrylic acid) using a photopolymerization approach. They applied poly(acrylic acid), \(NN^{\prime}\) methylene bisacrylamide (MB), and benzophenone as the monomer, crosslinker, and photo-initiator, respectively. The photopolymerization was conducted using a UV illumination system (UVITEK Crosslinker, Germany) at the wavelength of 365 nm, with the intensity of 1850 \(\mu\)W/cm\({}^{3}\) for one hour. The process resulted in transparent semi-IPN films with adjustable mechanical strength, water vapor, and oxygen permeation performance. They reported that the tensile strength and percent elongation of the film improved with increasing CA content. The water vapor transmission rate reduced with CA and the photo-initiator concentration and increased with monomer content. The in vitro studies  
Figure 2: Overall representation of fabricating and testing of thymoquinone-loaded PLA/CA nanocomposite. (**A**) SEM micrograph of nanofibers, (**B**) SEM micrograph of cells on nanofibers, (**C**) overall design on the construct, and (**D**) histopathological results. Reprinted with permission from Reference [46]. showed antibacterial and antifungal activities against _E. coli_ and _Aspergillus flavus_. The authors proposed that the physical properties of the semi-IPN film can be tailored for various wounds and loaded with different bioactive agents as the promising wound-healing biomaterial/dressing. [PERSON] et al. produced hydrogels by incorporating Ag NPs into poly(vinyl alcohol), CA, and gelatin. In these hydrogels, the amounts of loaded Ag NPs were different, and the diameter of produced nanocomposites was increased with the concentration of AgNO\({}_{3}\) loaded on the hydrogels. In fact, at concentrations of 5, 10, and 20 mM, yielded diameters were 38.6, 56.8, and 60.1 nm, respectively. The results of this study showed that these hydrogel membranes exhibited sufficient strength. These samples, formed by combining the polymers mentioned above and incorporation Ag NPs, showed higher thermal stability than single-polymer hydrogels and other sample groups. Additionally, Ag NPs in this hydrogel prevented the crystallization of PVA and the formation of NPs in the hydrogel. Moreover, Ag NPs induced long-term anti-microbial activity of these hydrogels against a wide range of fungi and bacteria. This anti-microbial activity was clearly higher in higher concentrations of AgNO\({}_{3}\). Overall, this study showed that these hydrogels are useful biomaterials for wound-healing and dressing applications. However, extensive studies have not treated these hydrogels' construction in much detail due to nanofibers' prominent features and the possibility of easily manipulating their structure, especially at small diameters, as mentioned earlier [51; 52]. Some other studies conducted on CA-based wound-healing biomaterials have been summarized in Table 1.