# Hyaluronic Acid-Based Wound Dressing with Antimicrobial Properties for Wound Healing Application
## 5 Conclusions and Future Perspectives  
HA plays crucial roles in the wound healing process, being a major constituent of all vertebrates' connective tissue ECM, promoting the formation of a fibrin clot and the production of interleukins and proinflammatory cytokines [40]. Thus, thanks to its hydrophilicity, biocompatibility and easily tuneable chemical properties, HA-based wound dressings have been produced so far in different compositions and shapes (scaffolds, films, fibers, non-woven fabrics, etc.). Moreover, HA shows strong bacteriostatic activity as it helps to reduce bacterial adhesion and biofilm formation [21], especially higher molecular weight HA [22]. It is a desirable property when dealing with wound healing since bacterial infections can delay healing processes. As a matter of fact, several surgical procedures dealing with regenerative medicine showed that the reduction in bacterial burden at the wound site thanks to bacteriostatic substance may improve the clinical outcomes [41]. Several papers give evidence that HA can show bacteriostatic effects on _staphylococci_ and _stretococci_, depending on HA concentration and molecular weight [22; 42], while _P. aeruginosa_ seems not to be affected by HA [7; 43]. However, HA intrinsic properties can be enhanced using synthetic and natural antimicrobial agents. Among synthetic dressings, AgNPs show a pervasive use in the literature, as they can be easily obtained with different approaches, also avoiding the use of organic toxic solvent [44]. Studies show effective antimicrobial activity in vitro, as well as in vivo and in clinical trials. Antibiotics can be regarded as antimicrobial synthetic agents. As an example, gentamicin sulphate can be coupled with bio-engineered substrates for wound healing. Alternatively, natural agents such as \(\varepsilon\)-polylysine and quaternized chitosan can be used as antimicrobial activity enhancers. One of the most promising solutions is curcumin, a natural phenolic substance proven to possess strong antibacterial properties. Moreover, AMP, a new class of antimicrobial drugs, is expected to potentially solve the problem of toxicity, as well as of antibiotic drug resistance.  
In the near future, some aspects involving the production of substrates for wound healing need to be further addressed. Particular attention should be given to a solvent-free fabrication in order to avoid the use of toxic organic solvents. In parallel, the production of more morphologically complex substrates should be addressed, focusing, as an example, on non-woven fabrics' substrates, whose properties seem to be interestingly adjusted by acting on composition, fiber density and orientation, or order of layering. Furthermore, to allow their successful commercialization, a reproducible process to produce HA derivatives is required, and their pharmacokinetic/pharmacodynamic properties must be optimized. In addition, the biological activity of HA-based wound dressings could be improved through the incorporation of other biomolecules such as adhesive proteins (e.g., fibronectin, laminin, fibrinogen) and/or stem cells for accomplishing an improved healing process.  
Conceptualization, F.D.S. and A.B.; investigation, G.L.; writing--original draft preparation, G.L. and F.D.S.; writing--review and editing, F.D.S., G.L., M.d.G., A.F. and A.B.; visualization, F.D.S., G.L., M.d.G., A.F. and A.B.; supervision, A.B. All authors have read and agreed to the published version of the manuscript.  
This research received no external funding.  
Not applicable.  
The authors declare no conflict of interest.