## 6 Clinical and Pre-Clinical Studies  
To the best of our knowledge, there are not yet any published reports describing clinical studies using chitosan/graphene oxide (CS/GO) hydrogels as wound dressings. There are some pre-clinical in vitro and in vivo studies in this field. For example, in one study, superior acute-wound healing was observed when CS/GO nanofibers were implanted in adult male rats [75]. The CS/GO nanofiber webs were prepared without any surfactants and organic solvents to make sure that the fibrous structure had excellent biocompatibility. In vitro evaluations with human skin fibroblasts indicated that the addition of GO \begin{table}
\begin{tabular}{c c c c} \hline
**Ingredients** & **Potential Applications** & **Characterization** & **Reference** \\ \hline \multirow{3}{*}{Chitosan/reduced GO} & \multirow{3}{*}{Transdermal drug delivery} & Enhanced electrical conductivity & \multirow{3}{*}{[67]} \\  & & pH dependent release behavior & \\  & & rGO reduced biodegradation rate & \\  & & Improved mechanical properties & \\ \hline \multirow{3}{*}{Chitosan/modified GO} & \multirow{3}{*}{Drug carrier} & Stability in aqueous acidic and & \multirow{3}{*}{[68]} \\  & & physiological solutions & \\  & & Biocompatible & \\  & & Excellent dispersibility & \\ \hline Aldehyde-conjugated chitosan/GO & Controlled chemical & Improved mechanical properties & \multirow{3}{*}{[69]} \\  & & release & Time-dependent aromatic release & \\ \hline Chitosan/hydroxyethyl cellulose/GO & Drug delivery application & Stability over all pH ranges & \\  & & application & Biocompatibility & \\ \hline \multirow{3}{*}{Chitosan/GO} & Delivery of & Nontoxic to kidney cells & \multirow{3}{*}{[71]} \\  & & Prosontocyanities * & Thermostable & \\  & (Ext.) & Biocompatibility of Ext. increased & \\ \hline \multirow{3}{*}{Chitosan/GO/Dextran} & \multirow{3}{*}{Anti-cancer drug delivery} & Increase release in acidic medium & \multirow{3}{*}{[72]} \\  & & (pH sensitivity behavior observed) & \\ \cline{1-1}  & & Strong cytotoxicity to cancer cells & \\ \cline{1-1}  & & Non-specific protein adsorption & \\ \hline \multirow{3}{*}{Galactosylated chitosan/GO} & \multirow{3}{*}{Drug delivery system for therapeutic treatment of cancer} & Stable in physiological conditions & \multirow{3}{*}{[73]} \\ \cline{1-1}  & & Higher fluorescence intensity in & \\ \cline{1-1}  & & tumor cells & \\ \cline{1-1}  & & Greater tumor cytotoxicity and better & \\ \cline{1-1}  & & tumor growth inhibition compared & \\ \cline{1-1}  & & to GO/GO derivatives & \\ \hline \multirow{3}{*}{Chitosan/Silver Nanoparticle/GO} & \multirow{3}{*}{Multi-Drug delivery} & pH controlled single and/or dual & \multirow{3}{*}{[74]} \\ \cline{1-1}  & & drug release & \\ \cline{1-1}  & & Strong antibacterial ability & \\ \hline \end{tabular}
\end{table} 
Table 3: Application of chitosan/GO films to serve as drug delivery systems. improved cell viability with enhanced bactericidal capacity. In vivo wound healing studies on rat's skin demonstrated faster healing and full recovery of a 1.5 \(\times\) 1.5 cm\({}^{2}\) open wound within 14 days. It is therefore recommended that these experimental CS/GO nanofiber webs have potential use in biomedical applications. Other experimental wound dressings have been fabricated by incorporating polyhexamethylene guanidine and modified graphene oxide (mGO) into a polyvinyl alcohol/chitosan film [3]. In this in vivo study, cytotoxicity and wound healing were evaluated by applying HaCaT immortalized human keratinocyte cells to murine-infected full-thickness skin wounds. The results of the cytotoxicity test demonstrated good biocompatibility, and the films generated rapid wound healing through faster re-epithelialization. However, by increasing the concentration of mGO up to 1 wt%, the proliferation of the HaCaT cells was prevented, and lower cytotoxicity was observed. In another in vivo study, rapid healing of dermal wounds was observed using a prototype wound dressing made of chitosan/L-polylactic acid/GO nanofibers [55].