# Cellulose Nanofibers and Other Biopolymers for Biomedical Applications. A Review
## 4 Outline of Biomedical Applications
### Wound Healing  
Wound dressings act as barriers, permeable to oxygen and moisture, which are not only essential to the healing process, but also protect the area from further harm-mainly the risk of infection from microorganisms. Biopolymers, such as cellulose, have been used in wound dressings as they have exhibited useful properties. They protect the skin outside the wound, maintain suitable moisture at the wound level, prevent and control microbial biofilms, cleanse the injured tissues, eliminate/minimise pain, remove dead spaces and non-viable tissues and control odours [135]. Biopolymer hydrogel dressings are used widely because of their ability to hold moisture and closeness to the ECM, helping to induce wound healing. In recent years, nanocellulose has been investigated to be used as potential material for wound healing application, due to its high surface to volume ratio that can enhance the proliferation, migration and attachment of cells. The high concentration of -OH groups in the surface of the nanocellulose offers a hydrated layer over the wounds. The application of nanocellulose to wound healing was recently reported in several studies [136; 137; 138; 139; 40; 140; 136; 139]. Nanocellulose, in combination with antibiotic agents (polyhexamethylene biguanide and tetracycline hydrochloride), was used to obtain bioactive wound dressing to prevent the colonisation of bacterial strips, especially _Staphylococcus aureus_ and _Escherichia coli_[138; 140]. The controlled release of drugs contained in wound dressings allowed the healing process in burn victims to be completed in the period of 10-16 days [139; 141]. Regarding the utilisation of nanocellulose for this application, no cytotoxicity of CNF obtained by TEMPO-mediated oxidation against 3T3 cell lines and human skin cells has been reported by several authors [142; 53; 143]. In addition, the matrix of nanocellulose and other polymers has been used successfully in wound dressings. Chitosan/PVP/Nanocellulose composite dressing in combination with stearic acid was used as temporary biological wound healing material on albino rats, revealing a healing process faster than the control wounds [144]. Hydrogels of nanocellulose and polydopamine crosslinked physically with Ca\({}^{2+}\) resulted in an excellent drug release for wound healing process, showing good antibacterial properties against different bacteria [140]. The addition of PEG as plasticiser into nanocellulose films improved the mechanical properties of nanocellulose wound dressings and increased the swelling of  
Figure 12: Scanning Electron Microscopy images of silk fibroin scaffolds obtained using different electrospinningnticentrations: 7 wt % (**A**), 8 wt % (**B**) and 9 wt % (**C**). Scale bars: 10 \(\upmu\)m. Reproduced with permission from [PERSON] et al. [131]. the wound dressing to 600% and 1000% in PBS and water, respectively [143]. Moreover, no effect in the metabolic activity was reported by the addition of PEG when fibroblasts were incubated when amounts of 10 and 25% were used; however, it was detected in the presence of 40% [143]. Additionally, no significant cell death was detected in any amount of PEG. Several biopolymers can be used for this application. For instance, chitosan has been investigated and deemed suitable for wound dressings by the US Food and Drug Administration (FDA). Low molecular weight Chitosan has been shown to have antimicrobial properties through testing against several bacteria present in human wounds. Chitosan also induces wound healing through fibroblast activation by way of releasing \(N\)-acetyl-beta-d-glucosamine into the wound site. Haemostatic and analgesic effects have also been observed [145; 146]. Figure 13 shows an example of a chitosan-alginate wound dressing. Biopolymer wound dressings can also be impregnated with antimicrobials, such as antibiotics or silver to help manage chronic wounds--these are termed 'active dressings'.