# A Review of Properties of Nanocellulose, Its Synthesis, and Potential in Biomedical Applications
## 6 Biomedical Applications of Nanocellulose
### Wound Healing  
Hemostasis, inflammation, granulation, proliferation, maturation, or remodeling are all processes that occur during wound healing. Consequently, materials based on nanocellulose are potentially used to address each stage by acting as an antimicrobial, anti-inflammatory, or hemost agent; the incorporation of growth factors and cytokines is allowed to encourage angiogenesis and re-epithelialization. For wound dressing and wound healing applications, the basic needs should be met by the desirable nanocellulose materials such as (a) ought to be non-toxic and biologically active, devoid of anphylactogen and pyrogen; (b) highly permeable for the uptake of blood, diffusion of the drug, and gas transmission; (c) competent for controlling the microenvironment (pH, moisture, and temperature) in the wound area; and (d) effective against the pathogen and infection [176; 177].  
Because of its exciting and unique characteristics, such as high biocompatibility, excellent water holding capacity, and high purity, bacterial cellulose is intensively researched and utilized as a compatible biomaterial for wound healing and repair. Figure 4e,f show the potential application and wound healing rate using nanocellulose bio-nanocomposites.  
Nanocellulose is used to patch acute burns with artificial skin, regulate chronic wound healing with dressing, and mold synthetic blood vessels in reconstructive surgeries. Integrating biologically active substances, including inorganic salts, chitosan, antibiotics, organic metals, or natural plant products, can provide antibacterial properties [178; 179]. Other forms of nanocellulose, such as CNC and CNF, were also investigated for potential application in wound dressing and healing, but often in composite or modified forms. For example, a multipurpose hydrogel was constructed using genipin crosslinking diosgenin and gelatin to make a semi-IPN composite. The hydrogel showed non-cytotoxicity, high mechanical characteristics, and effective antimicrobial capabilities, which are essential in the healing process to speed up wound healing and avoid infection [180].  
Nanocellulose-based scaffolds with a controllable stiffness were printed by using a 3D printer and crosslinked by employing a dual crosslinking approach, a chemical crosslinking with 1,4-butanediol diglycidyl ether and in situ calcium (Ca\({}^{2+}\)) crosslinking, to govern the rigidity of the scaffold, which has been found to influence the cellular behavior during wound healing [181]. A dual crosslinking approach involving UV crosslinking and in situ Ca\({}^{2+}\) crosslinking was developed to print skin patches to provide excellent printability while using low nanocellulose inks. The nanocellulose-based hydrogel integrated gelatin methacrylate was reported to aid the design process and encourage the proliferation of cells [182].  
Figure 4: Nanocellulose-based biomedical applications. (**a**) Different sized bacterial synthesized cellulose tubes. Adapted with permission from Ref. [163]. (**b**) Vascular prosthesis implant consisting of polyurethane/nanocellulose for treating multiple endocrine neoplasia 2B. Adapted with permission from Ref. [183]. (**c**) Confocal micrograph of localization of ALP protein (green) in RBMSCs after treatment with nanocellulose-based scaffold for 7 and 14 days to assess the effect of VEGF and BMP2 growth factors. (**d**) Fluorescence microscopy images of bMSCs growing on chitosan/CNC nanofibers. Adapted with permission from Ref. [184]. (**e**) Images of wound treated with control, CP-S (Chitosan/polyvinyl pyrrolidone-stearic acid), and CPNC 3% (Chitosan/polyvinyl pyrrolidone/nanocellulose-stearic acid 3%). (**f**) The wound healing rate of control, CP-S, and CPNC3%-S bio-nanocomposite. * Considerably difference compared to the control group (\(p<0.05\)). Adapted with permission from Ref. [185].