Title: Prophylaxis of implant-related infections by local release of vancomycin from a hydrogel in rabbits

Authors: W Boot, HC Vogely, PGJ Nikkels, B Pouran, MHP van Rijen, MB Ekkelenkamp, GM Hänsch, WJA Dhert, D Gawlitta

Address: UMC Utrecht, Heidelberglaan 100 3584 CX, Utrecht, the Netherlands

E-mail: w.boot at umcutrecht.nl

Abstract: Local prophylaxis with antibiotic-loaded bone cement is a successful method to prevent post-operative infections in patients receiving orthopaedic implants. No comparable method is available for uncemented implants. Therefore, a hydrogel consisting of hyaluronic and polylactic acids was evaluated in a rabbit model for delivery of antimicrobial agents to prevent post-operative infections.
In a pilot study, the suitability of the in vivo model was assessed by testing the hydrogel as carrier material for antimicrobial agents.In the main study, the antimicrobial-agent-loaded hydrogel was evaluated for infection prophylaxis. Rabbits received a titanium rod intramedullary in the tibia after contamination with Staphylococcus aureus. The rods were coated with unloaded hydrogel (Gel), hydrogel loaded with 2 % (Van2) or 5 % vancomycin (Van5), bioactive glass (BAG) or N-acetyl-L-cysteine (NAC). To analyse the infection severity after 28 d, histopathological, bacteriological, micro-computed tomographic and haematological analyses were performed.
In the pilot study, the Van5 group had less infection (0/6 infected) as compared to the Gel group (5/5, p = 0.000) and the in vivo model was deemed suitable. In the main study, in the Van2 and Van5 groups, the number of infected animals was lower [1/6 (p = 0.006) and 2/6 (p = 0.044) infected, respectively]. In contrast, BAG and NAC groups showed no infection reduction (5/6 both groups, p = 0.997).
The hydrogel can be used as a local carrier of vancomycin for prophylaxis of implant-related infections.The present study showed promising results for local delivery of antibacterial agents by hydrogel to prevent implant-related infections.

Key Words: Implant-related infection, prophylaxis, in vivo, hydrogel, local delivery, vancomycin.

Publication date: February 19th 2020

Article download: Pages 108-120 (PDF file)
DOI: 10.22203/eCM.v039a07