Hyaluronic Acid and Its Composites as a Local Antimicrobial/Antiadhesive Barrier

Abstract

Living in biofilms is probably the most common condition for bacteria and fungi and biofilm-related infections account for the majority of bacterial infectious diseases worldwide. Among others biofilm-related infections, those associated with implanted biomaterials have an enormous and still largely underestimated impact in orthopaedics and trauma, cardio-surgery and several other surgical disciplines. Given the limited efficacy of existing antibiotics in the prevention and treatment of bacterial biofilms, new strategies are needed to protect implants and host tissues, overcoming the striking ability of the microorganisms to adhere on different surfaces and to immediately protect themselves by forming the biofilm matrix. Adhesion is a necessary first step in microbial colonization and pathogenesis and provides a potential target for new preventive and treatment approach. Among various polymers, tested as antibacterial coatings, hyaluronic acid and some of its composites do offer a well-established long-term safety profile and a proven ability to reduce bacterial adhesion and biofilm formation. Aim of the present review is to summarize the available evidence concerning the antiadhesion/antibiofilm activity of hyaluronic acid and some of its derivatives to reduce/prevent bacterial adhesion and biofilm formation in various experimental and clinical settings.

Keywords: Adhesion; Bacteria; Biofilm; Hyaluronic Acid; Implant; Infection.

Figure 1

DAC^® hydrogel application on a titanium acetabular cup prosthesis (A). The hydrogel comes in powder form in a prefilled syringe and is designed to be reconstituted at the time of surgery with water for injection. Scanning Electron Microscope (SEM) analysis of sandblasted titanium samples surface (magnification 10,000x) without the hydrogel coating (B) or after DAC^® coating (C) and mechanical scraping of the hydrogel to test its ability to resist press-fit insertion. Note the complete and uniform coverage of the titanium surface.

Figure 2

Adhesion densities of S. aureus (mean CFU/cm² ± standard deviation) to discs pre-treated with DAC^® (“Defensive Antibacterial Coating”, Novagenit Srl, Mezzolombardo, Italy) and controls at 15, 30, 60 and 120 min; *** P < 0.001 (two-way ANOVA followed by Bonferroni post hoc test).

Figure 3

Adhesion densities of S. aureus (mean CFU/cm² ± standard deviation) over time in pre-treated with DAC^® and control discs at 15, 30, 60, 120 min; * 0.01 < P <0.05, ** 0.001 < P < 0.01, *** P < 0.001 (two-way ANOVA followed by Bonferroni post hoc test).

Figure 4

Adhesion densities on discs with of S. aureus (mean CFU/cm² ± standard deviation) applied before DAC treatment and controls at 15, 30, 60, 120 min; * 0.01 < P <0.05, *** P < 0.001 (two-way ANOVA followed by Bonferroni post hoc test).

Figure 5

Adhesion densities over time on discs with of S. aureus (mean CFU/cm² ± standard deviation) applied before DAC treatment and controls at 15, 30, 60, 120 min; * 0.01 < P <0.05, ** 0.001 < P < 0.01, *** P < 0.001 (two-way ANOVA followed by Bonferroni post hoc test).

Figure 6

Comparison of the efficacy of DAC hydrogel, gentamicin, vancomycin or a combination thereof, on biofilm formation reduction of Staphylococcus aureus (A. and B.) and Staphylococcus epidermidis (C. and D.) over time (hours). Note that the hydrogel alone is able to provide an equal or superior biofilm reduction compared to commonly used antibiotics, while a synergistic effect is observed using a combination of the hyaluronic acid based hydrogel and the antibiotic compounds.

Figure 6

Comparison of the efficacy of DAC hydrogel, gentamicin, vancomycin or a combination thereof, on biofilm formation reduction of Staphylococcus aureus (A. and B.) and Staphylococcus epidermidis (C. and D.) over time (hours). Note that the hydrogel alone is able to provide an equal or superior biofilm reduction compared to commonly used antibiotics, while a synergistic effect is observed using a combination of the hyaluronic acid based hydrogel and the antibiotic compounds.