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. 2022 Mar 10;33(3):30.
doi: 10.1007/s10856-022-06650-x.

Treatment of vascular graft infections: gentamicin-coated ePTFE grafts reveals strong antibacterial properties in vitro

Igor Lazic #  1 , Andreas Obermeier #  2 , Bettina Dietmair  2 , Wolfgang E Kempf  3 , Albert Busch  3 , Jutta Tübel  2 , Jochen Schneider  4 , Rüdiger von Eisenhart-Rothe  2 , Peter Biberthaler  5 , Rainer Burgkart  2 , Dominik Pförringer  5
Affiliations

Treatment of vascular graft infections: gentamicin-coated ePTFE grafts reveals strong antibacterial properties in vitro

Igor Lazic et al. J Mater Sci Mater Med. .

Abstract

Vascular graft infections (VGI) are severe complications in prosthetic vascular surgery with an incidence ranging from 1 to 6%. In these cases, synthetic grafts are commonly used in combination with antimicrobial agents. Expanded polytetrafluoroethylene (ePTFE) is in clinical use as a synthetic graft material and shows promising results by influencing bacterial adhesion. However, the literature on antibiotic-bound ePTFE grafts is scarce. Gentamicin is a frequently used antibiotic for local treatment of surgical site infections, but has not been evaluated as antimicrobial agent on ePTFE grafts. In this study, we examine the antimicrobial efficacy and biocompatibility of novel types of gentamicin-coated ePTFE grafts in vitro. ePTFE grafts coated with gentamicin salt formulations with covalently-bound palmitate were evaluated in two drug concentrations (GP1.75% and GP3.5%). To investigate effects from types of formulations, also suspensions of gentamicin in palmitate as well as polylactide were used at comparable levels (GS + PA and GS + R203). Antibacterial efficacies were estimated by employing a zone of inhibition, growth inhibition and bacterial adhesion assay against Staphylococcus aureus (SA). Cytotoxicity was determined with murine fibroblasts according to the ISO standard 10993-5. Gentamicin-coated ePTFE grafts show low bacterial adherence and strong antibacterial properties in vitro against SA. Bactericidal inhibition lasted until day 11. Highest biocompatibility was achieved using gentamicin palmitate GP1.75% coated ePTFE grafts. ePTFE grafts with gentamicin-coating are effective in vitro against SA growth and adherence. Most promising results regarding antimicrobial properties and biocompatibility were shown with chemically bounded gentamicin palmitate GP1.75% coatings. Graphical abstract.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Different geometrical types of vascular graft samples for zones of inhibition testing. Left and middle: cylindrical samples on Agar, incubated with S. aureus overnight. Right: circular stamped samples. The lower row of pictures shows uncoated ePTFE-controls without any recognizable inhibition zone
Fig. 2
Fig. 2
Gentamicin-release in PBS solution over 48 h for vascular graft coatings using gentamicin in various formulations
Fig. 3
Fig. 3
Zones of inhibition against SA using circular and cylindrical samples of gentamicin-coated ePTFE grafts. A circular coated samples with GP1.75%, GP3.5%, GS + PA and GS + R203. B cylindrical samples of gentamicin-coated ePTFE grafts with GP1.75% and GP3.5%
Fig. 4
Fig. 4
SA growth inhibition in bacterial suspension with circular probes of untreated, non-gentamicin, and gentamicin-coated ePTFE grafts
Fig. 5
Fig. 5
Numbers of adhered SA on untreated, non-gentamicin and gentamicin-coated ePTFE grafts
Fig. 6
Fig. 6
Metabolic activity of murine fibroblasts (L929) using a WST-1 assay. L929 were challenged with the DMEM elution of untreated, non-gentamicin and gentamicin-coated ePTFE grafts respectively (n = 7). Dotted line indicates the limit of tolerated loss of activity at 70% according to the ISO 10993-5 standard for medical devices
Fig. 7
Fig. 7
SEM pictures of uncoated and various gentamicin-coated ePTFE grafts (left) and with SA incubated grafts (right) exemplarily after 24 and 48 h. A Non-coated ePTFE graft (×1000); B, D ePTFE graft (×3000) after SA inoculation time; C, E, G, I diverse coated surfaces for GS + PA, GS + R203 and GP variants; F, H, J show GP coating variants after 24 and 48 h of SA exposure at 37 °C indicating highly reduced numbers of adhered SA compared to uncoated ePTFE graft (B + D)
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