Bactericidal activity of 3D-printed hydrogel dressing loaded with gallium maltolate

Abstract

Chronic wounds are projected to reach epidemic proportions worldwide because of the aging population and the increasing incidence of diabetes. Despite extensive research, infection remains one of the leading sources of complications in chronic wounds, resulting in improper healing, biofilm formation, and lower extremity amputation. To address the limitations of standard treatments, we have developed a hydrogel wound dressing with self-tuning moisture control that incorporates a novel antimicrobial agent to eliminate and prevent infection. 3D-printing of a hydrogel dressing with dual porosity resulted in a new dressing with greater flexibility, increased water uptake, and more rapid swelling than bulk hydrogel dressings. Additionally, gallium maltolate (GaM) was incorporated into the dressing to investigate the efficacy of this antimicrobial agent. Loading profiles, release kinetics, and the bactericidal activity against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus ) of GaM were investigated in vitro to identify target profiles that supported infection control. Finally, GaM-loaded hydrogel dressings were evaluated in vivo , utilizing a murine splinted-wound model that was inoculated with S. aureus . In comparison to an untreated control, GaM dressings markedly reduced the wound bacterial load without compromising wound closure rates. Overall, this work demonstrates the utility of a 3D-printed hydrogel dressing as an antimicrobial dressing to control infection in chronic wounds.

Comparative efficacy of resorbable fiber wraps loaded with gentamicin sulfate or gallium maltolate in the treatment of osteomyelitis

“…Despite these differences, the daily dose of gentamicin sulfate and gallium maltolate released were greater than the respective MICs reported for S. aureus over 72 h (Figure 2). 24,34 These results demonstrated that electrospun PLGA wraps enable the incorporation and controlled release of a diverse portfolio of antimicrobials at therapeutic concentrations.…”

“…The measured MIC of gallium maltolate was 6000 μM and was also discovered to be higher than the MIC reported by Cereceres et al (Figure 4(b)). 34 The MBC was not assessed as it exceeded the solubility limit in RPMI. Although these results confirm that gallium maltolate is able to inhibit growth of MSSA, the released concentrations from the PLGA wrap (mesh mass = 160.1 ± 0.3 mg; gallium maltolate mass = 32.1 ± 0.1 mg; 2 ml DI water) were below this value and unable to eradicate MSSA infection.…”

“…Polymer solutions were formulated with gentamicin sulfate at 1.25% of the polymer mass, gallium maltolate (Gallixa LLC, Menlo Park, CA) at 25% of the polymer mass, or without the incorporation of an antimicrobial agent (blank). The concentration of gentamicin sulfate and gallium maltolate blended with the PLGA was determined based on the release kinetics obtained from preliminary scouting studies (results not included) and reported minimum inhibitory concentrations (MIC; lowest concentration that visibly inhibited bacteria growth) of gentamicin sulfate and gallium maltolate 24,34 . The PLGA solutions were electrospun at ambient conditions (22°C, 40%–50% relative humidity).…”

“…Gallium maltolate was selected as a new antimicrobial for osteomyelitis treatment due to its ability to mimic the ferric ion which allows it to disrupt the iron‐dependence of microorganisms and inhibit growth 33 . To date, the antimicrobial potential of gallium maltolate has been demonstrated in chronic wound applications but not in osteomyelitis applications 34,35 . This study provides a direct comparison of the bactericidal activity of gentamicin sulfate and gallium maltolate by identifying the minimum inhibitory concentration and minimum bactericidal concentration on bacterial isolates from osteomyelitis.…”

Assaying How Phagocytic Success Depends on the Elasticity of a Large Target Structure

“…The synthesis of PEG diacrylate (PEGDA) was adapted from a published protocol (35). All materials for this synthesis were purchased from Sigma-Aldrich, unless stated otherwise.…”