## 3 Discussion
aureus_[161; 162] and has been found to be superior to LL-37 in inhibiting biofilm under saline environmental conditions [162]. This would overcome the limitations of using LL-37 due to environmental factors, but studies demonstrating an effect on wound healing are still lacking. We believe that this molecule deserves further in vivo studies before clinical application. Better results on biofilm control can be achieved by combining AMPs with different mechanisms of action, as well as AMPs and antibiotics. In a mouse model study [165], topical RIP plus Temporin A, an AMP effective against biofilm and promoting wound healing [166], was shown to result in better control of glycopeptides-intermediate _S. aureus_-infected wounds compared with monotherapy and rifampicin. This study suggests that the combination of an anti-QS agent and a specific anti-biofilm agent further increases efficacy against antibiotic-resistant staphylococci. Another interesting molecule is 1.037, a synthetic peptide of 9 amino acids, which can inhibit biofilm formation in staphylococci by increasing bacterial motility and reducing the expression of genes responsible for biofilm formation and QS but has little antimicrobial activity [161]. Even in this study, data on an in vivo model of wound healing are lacking. In our opinion, the combination of AMPs and other molecules with a different mechanism of action could be, in the next future, the solution for difficult multifailure conditions. We also want to mention bacteriocins, ribosomally synthesized bacterial peptides with important activity against staphylococcal biofilm. For example, Garvicin KS and microcin P1 showed in vitro anti-biofilm activity against both MSSA and MRSA. It was also observed that the combination of these two bacteriocins reduced MRSA resistance to penicillin G, revealing both antibioofilm and anti-MRSA activity [167]. The use of these molecules may therefore help to make antibiotics effective against resistant strains, although there is a lack of studies on wound healing. With regard to _S. epidermidis_, one study [168] showed that Nisin A M17Q, a bacteriocin-derivative produced by Lactococcus lactis, can inhibit biofilm formation and the growth of _S. epidermidis_ in an in vitro wound model more than wild type Nisin A. [168] This is one of the few studies considering the action of biofilm-producing _S. epidermidis_ on wounds, although in an in vitro model [168]. Further animal studies and comparisons with other promising molecules are needed to assess its effective action on wound healing. Other molecules have promising actions against staphylococci in the literature, in particular, defensins, proteins that mediate the innate immunity of organisms against bacteria. One example is the defensin-like peptide (DLP)-P2, a fungal-derived molecule that was shown to be effective in controlling multidrug-resistant _S. aureus_ infections and biofilm formation both in vitro and in a mouse model with peritoneal infection [169]. A study of wound healing has not been carried out, but the prospects for using this molecule are interesting, especially in cases with extreme resistance to antibiotics. Regarding the most common topical dressings already known, in a study by [PERSON] et al. [170] their anti-biofilm efficacy was evaluated in an in vitro model of _S. aureus_ and _S. epidermidis_. Referring to inhibition of biofilm formation, dressings without antimicrobial agents and with only alginate fibres, carboxymethylcellulose (CMC), cotton, or hydrocellular foam proved ineffective or poorly effective. Conversely, dressings with antimicrobial agents such as povidence-iodine (PVP-iodine), hydroactive colloid gel, silver dihydrogen citrate, fusidic acid (20 mg/g) and polyhexanide have been effective in preventing biofilm formation. Finally, dressings containing ionic silver, metallic silver and silver sulphate, silver sulphadiazine, PVP-iodine (10 g/100 mL) and ozonated olive oil were effective in inhibiting biofilm formation.