# Hyaluronic Acid-Based Wound Dressing with Antimicrobial Properties for Wound Healing Application
## 4 HA-Based Devices Combining Natural Antimicrobial Agents
\begin{table}
\begin{tabular}{c c c c} \hline \hline \multicolumn{1}{c}{**Antimicrobial Agent**} & \multicolumn{1}{c}{**Type of HA Wound Dressing**} & **Tested Pathogens** & **Reference** \\ \hline \multirow{8}{*}{Silver Nanoparticles (AgNPs)} & Wound healing ability of different MW of hyaluron; & & \\  & in vivo study. & - & [29] \\  & Hydrogel & & \\ \cline{2-4}  & HA and metallic silver treatment of chronic wounds: & & \\  & healing rate and bacterial load control; clinical trial. & - & [30] \\  & Spray powder & & \\ \cline{2-4}  & Antibacterial thermosensitive hydrogels based on corn & _B. subtilis_ & \\  & silk extract, HA and nanosilver improving wound & _S. aureus_ & [13] \\  & healing with antimicrobial properties. & _P. aeruginosa_ & \\  & _E. coli_ & \\ \hline \multirow{8}{*}{Gentamicin Sulphate} & Antimicrobial activity of a blend of & _S. aureus_ & \\  & collagen/chitosan/HA with gentamicin sulphate. & _E. coli_ & [31] \\  & Film & _P. aeruginosa_ & \\ \hline \multirow{8}{*}{Antimicrobial Peptides (AMPs)} & Biofunction of antimicrobial peptide-conjugated & _E. coli_ & \\  & alginate/HA/collagen resulting in significant inhibition & Methicillin-resistant & [32] \\  & of bacteria in infected wounds with rapid healing & _Staphylococcus aureus_ & \\  & Scaffold & (MRSA) & \\  & & _S. aureus_ & \\ \hline \multirow{8}{*}{Curcumin} & Wound healing ability of curcumin conjugated to HA; & & \\  & in vitro and in vivo evaluation. & MRSA & [34] \\  & Scaffold & & \\ \cline{2-4}  & Curcumin-grafted HA-modified pullulan polymers as a & _S. aureus_ & \\  & functional wound dressing material. & _E. coli_ & [37] \\  & Film & & \\ \hline \multirow{8}{*}{\(\varepsilon\)-polylysine} & Dual crosslinked hyaluronic acid/\(\varepsilon\)-polylysine hydrogel with self-healing and antibacterial properties for wound & & [38] \\  & healing polymers; in vivo study. & & \\  & Hydrogel & _E. coli_ & \\ \hline \multirow{8}{*}{Quaternized chitosan} & Antimicrobial hyaluronic acid/quaternized chitosan hydrogels for the promotion of seawater-immersion & _S. aureus_ & [39] \\  & wound healing. & & \\ \cline{1-1}  & Hydrogel & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Different types of HA-based devices combining both synthetic and natural antimicrobial agents with proven antimicrobial activity. Another antimicrobial bioadhesive hydrogel for wound dressings with inherent antibacterial properties was fabricated by mixing modified HA and \(\varepsilon\)-polylysine (EPL). Hydrogels were produced using the aldehyde form of HA (HA-CHO), by mixing 0.5% (\(w/w\)) HA solution to an equal molar NaIO\({}_{4}\) solution dropwise. After 2 h reaction, it was terminated by adding 1 mL ethylene glycol into the system for another 1 h. Instead, EPL and levodopa were dissolved into an enriched ethanesulfonic acid (MES) solution. Antimicrobial properties were tested through haematoxylin and eosin staining, Masson staining, and \(\alpha\)-SMA and CD31 staining. Results showed how such hydrogels were able to kill both Gram-positive and Gram-negative bacteria thanks to their high-density positive charge [38] (Table 1). Novel hydrogels based on the combination of natural polymers have been designed for the treatment of various wounds. A composite hydrogel made up of HA and quaternized chitosan (QCS) has been fabricated in order to find a solution for wound healing in the presence of seawater, containing high quantities of sodium and potentially dangerous bacteria. Hydrogels were produced and dialyzed using the HA-CHO, as conducted in the previous example. To produce hydrazide-modified HA, HA was dissolved in distilled water and then ADH was added. To this solution a DMSO/H\({}_{2}\)O solution (volume ratio 1:1) with EDC and HoBt was subsequently added. The reaction was terminated by adding NaOH solution. HA-ADH solution was then precipitated in ethanol and dialyzed after redissolution in a dialysis sack. The antimicrobial activity of QCS is given both by chitosan and by the addition of quaternary ammonium.