**3. Clinical applications of HA to prevent bacterial adhesion**

Several clinical local applications of HA to reduce the impact of biofilm-related infections have been reported with favorable results and no adverse events [37].

Torretta et al. [38] recently described topical administration of hyaluronic acid in children with recurrent or chronic middle ear inflammations and chronic adenoiditis.

Other studies have documented the positive effect of topical HA in chronic urinary tract infections (UTI). At variance with current antibiotic treatments, aimed at eradicating pathogens, HA local administration targets bacterial adherence to the bladder mucosa [39–42]. Damiano et al., in a prospective, randomized, double-blind, placebo-controlled study, showed a significant reduction of 77% (P < 0.0002) in the UTI rate per year in HA-treated patients, compared to controls. Moreover, mean time to UTI recurrence was significantly prolonged (185.2 ± 78.7 vs. 52.7 ± 33.4 days, P < 0.001) after HA treatment, compared with placebo [43]. No adverse events were reported. A recent multicenter European study confirmed the efficacy of intravescical administration of combined HA and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections [44].

In dentistry, the effect of the application of HA-containing gels in early wound healing after scaling and root planing (SRP) on clinical variables, subgingival bacteria and local immune response was investigated [45, 46]. Eick et al. [47] reported on 34 individuals affected by chronic periodontitis and treated with full-mouth SRP; in the test group (n = 17), a 0.8% hyaluronan-containing gel was introduced into all periodontal pockets during SRP and a 0.2% HA gel was applied by the patients onto the gingival margin twice daily during the following 2 weeks, while the control group (n = 17) was treated with SRP only; no placebo was used. Probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and after 3 and 6 months, and subgingival plaque and sulcus fluid samples were taken for microbiologic and biochemical analysis. The changes in PD and the reduction of the number of pockets with PD ≥ 5 mm were significantly higher in the test group after 3 (P = 0.014 and 0.021) and 6 (P = 0.046 and 0.045) months. Six months after SRP, the counts of *Treponema denticola* were significantly reduced in both groups (both P = 0.043), as were those of Campylobacter rectus in the test group only (P = 0.028). *Prevotella intermedia* and *Porphyromonas gingivalis* increased in the control group. No adverse effects of HA were observed during the study.
