Abstract
Aim
To develop a new system for antibacterial coating of joint prosthesis and osteosynthesis material. The new coating system was designed to release gentamicin immediately after insertion to eradicate surgical contamination.
Method
Steel implants (2×15mm) were coated with a solid nanocomposite xerogel made from silica and the dendritic polymer, hyperbranched polyethyleneimine. The xerogel was anchored inside a porous surface made by pre-coating with titanium microspheres. Finally, gentamicin was encapsulated in the xerogel, i.e. no chemical binding. A total of 50 µg gentamicin was captured into each implant. The efficacy of the new coating was evaluated in a porcine model of implant associated osteomyelitis. In total, 30 female pigs were randomized into 3 study groups (n=10). Group A; plain implants + saline, Group B; plain implants + 104 CFU of Staphylococcus aureus, and Group C; coated implants + 104 CFU of S. aureus. Implant + inoculum was placed into a pre-drilled implant cavity of the right tibia and the pig was euthanized 5 days afterwards. Postmortem microbiology and pathology were performed. Two additional pigs were used in a pharmacokinetic study where microdialysis (MD) catheters were placed alongside coated implants. Extracellular fluid was sampled regularly for 24 hours from the MD catheters and analyzed for gentamicin content.
Results
Within Groups A and C, all implants were found sterile by sonication and bacteria could not be identified within the surrounding bone tissue. In contrast, all Group B animals had S. aureus positive implant and tissue microbiology. Macroscopic and microscopic pathological examinations confirmed that Group A and C animals were complete identic, i.e. no pus around implants and only minor peri-implant inflammation related to insertion of implants per se. All Group B animals had pus around their implants and a massive peri-implant inflammatory response dominated by neutrophil granulocytes. Maximum gentamicin release (35 µg /mL) was measured in the first obtained MD sample, i.e. after 30 min, and the concentration stayed above the MIC level for the used S. aureus strain for 8 hours.
Conclusions
The new xerogel coating prevented development of osteomyelitis. Prevention was due to a fast gentamicin release immediately following insertion and antimicrobial active concentrations were detectable several hours after implantation. This means that the critical time point of most relevant surgical procedures potentially could be protected by the novel coating. The new coating will be investigated on larger scale implants and full-size prosthesis in the future.
