# Hyaluronic Acid-Based Wound Dressing with Antimicrobial Properties for Wound Healing Application
## 3 HA-Based Devices Combining Synthetic Antimicrobial Agent  
HA possesses antimicrobials effective against different Gram-positive and Gram-negative bacteria [7; 11; 23]. However, such properties can be increased using antimicrobial agents. Among synthetic substances, the use of silver nanoparticles (AgNPs) is pervasive in the literature as they can be obtained quite easily, in numerous ways, which do not involve the use of potential toxic media.  
The effect of AgNPs on wound healing and antimicrobial effects once seeded in H MW HA (HA4) was reported (Table 1). Briefly, HA solutions were prepared by the dissolution of different molecular weights of HA in Milli-Q water at room temperature with continuous stirring; to produce AgNPs-enriched solutions, 1 mL of 10 mM of silver nitrate was added dropwise. When compared to the samples at L MW HA (HA1), M MW HA (HA3) and H MW (HA2) without nanoparticles, HA4 showed a reduction in wound size, improving granulation and inflammatory mediators in impaired older and diabetic wound healing. In particular, as regards the inhibition of pathogenic bacteria, both HA4 and HA2 were found to significantly arrest the number of pathogenic bacteria on wounds throughout the first 24 h in comparison to the control nontreated rats [29] (Figure 3).  
A clinical trial involving patients with a vascular ulcer confirmed the safety and wound healing activity of a topical spray powder containing HA sodium salt 0.2% and AgNPs 2.0%, an EC-certified class III medical device. Results showed that such a spray  
Figure 3: Total count of pathogenic bacteria grown on the full thickness wounded skin from older untreated (control, CN) and treated rats. * Indicated the significance in comparison with the control. Reprinted from [29]. Copyright 2016, with permission from Elsevier.  
powder is effective not only in reducing wound area, due to the presence of HA, but in keeping the bacterial colonisation under control, showing a reduction in bacterial load (\(p<0.025\)) [30] (Table 1).  
Thermosensitive and injectable hydrogels based on HA, corn silk extract (CSE) and AgNPs were prepared and their potential use as a wound care material was investigated. Briefly, hydrogels were fabricated by the addition of HA to a blend of Pluronics F127 and F68 in CSE to obtain concentration 1% \(w/w\), while Ag NPs were biosynthesized by a microwave-assisted green technique using CSE in an organic solvent-free medium. Hydrogels exhibited antibacterial activity against Gram-positive (_B. subtilis, S. aureus_) and Gram-negative (_P. aeruginosa, E. coli_) bacteria. A wound healing in vitro assay revealed that the hydrogels allow faster wound closure and repair compared to the controls consisting of the single biomaterials (Table 1) [13].  
Moreover, in the literature the use of antibiotics coupled with bio-engineered scaffolds has been widely studied. An example are thin films made up of blended collagen, chitosan and HA fabricated by solvent evaporation after the addition of gentamicin sulphate, a common antibiotic for bacterial infections. In more detail, the HA solution (1% \(w/w\) in 0.1 M hydrochloric acid) was added in different ratios to chitosan and collagen mixtures (1% \(w/w\) in 0.1 M acetic acid). The antimicrobial activity of such films was tested against S. aureus (Gram-positive bacteria), _E. coli_ and _P. aeruginosa_ (Gram-negative bacteria) by using the diffusion method. Results showed a better efficiency for the samples in which gentamicin sulphate was released from polymeric matrixes, with inhibition zones of approximately 25-30 mm (Table 1) [31].