Gentamicin-loaded xerogel coating prevents peri‑prosthetic joint infection in an adult Göttingen minipig model

The risk of infection when inserting orthopedic devices like prostheses, screws, and plates represents a serious and challenging complication in orthopedic surgery. Most infections result from bacterial introduction during surgery, making it crucial and clinically relevant to protect the devices and surrounding tissue with intraoperative antimicrobials, especially in high-risk patients. Therefore, to mitigate this risk, antimicrobial coatings for different types of orthopedic devices have received substantial attention in recent decades with the goal of developing a “self-cleaning” surface. In here, we investigated a new and highly promising coating candidate. The coating was made of a hyperbranched poly(ethylene imine (PEI)) + orthosilicic acid-based hydrogel, that in a sol-gel process was transformed into a solid xerogel, which afterwards was loaded with gentamicin as active compound. The gentamicin-loaded xerogel coating was applied to functional implants i.e., cancellous bone screws, and tested within an advanced minipig model of Staphylococcus aureus induced peri‑prosthetic joint infection, without the use of systemic antimicrobial therapy. The study included evaluation of antimicrobial efficacy (quantification of bacterial load on the screw surface and within the surrounding tissues), pre -and post-insertion characterization of the coating, assessment of local inflammation and gene expression, and acute toxicity. Additionally, the pharmacokinetic in-vivo gentamicin release profile was measured using microdialysis in relevant local compartments. Due to a quick, locally high, and complete gentamicin release, the coating completely eradicated S. aureus from all compartments in all but one minipig. Therefore, this study shows proof of concept for the effectiveness of preventive antimicrobial release-based coatings.