Revisiting the "race for the surface" in a pre-clinical model of implant infection.

Orthopaedic implant use increases infection risk. Implant infection risk can be explained by the "race for the surface" concept, where there is competition between host-cell integration and bacterial colonisation. Although generally accepted, the temporal dynamics have not been elucidated in vivo. Using a bilateral intramedullary rat model, Staphylococcus aureus was injected into the tail vein either immediately after or 1, 3 and 7 d following implant placement. This allowed assessment of the temporal interplay between bacterial colonisation and host-cell adhesion by uncoupling implant placement and bacterial challenge. 2 weeks following inoculation, animals were anaesthetised, euthanised and implants and tissues harvested for bacterial enumeration. To assess host participation in implant protection, additional animals were not inoculated but euthanised at 1, 3 or 7 d and the host cells adhered to the implant were evaluated by flow cytometry and microscopy. As time between implant placement and bacterial challenge increased, infection rate and bioburden decreased. All implants had measurable bioburden when challenged at day 1, but only two implants had recoverable bacteria when inoculated 7 d after implant placement. This protection against infection corresponded to a shift in host cell population surrounding the implant. Initially, cells present were primarily non-differentiated stem cells, such as bone marrow mesenchymal stem cells, or immature haematopoietic cells. At day 7, there was a mature monocyte/macrophage population. The present study illustrated a direct relationship between host immune cell attachment and decrease in bacterial colonisation, providing guidance for antimicrobial release devices to protect orthopaedic implants against bacterial colonisation.

Chlorhexidine-releasing implant coating on intramedullary nail reduces infection in a rat model.

The use of internal intramedullary nails for long bone fracture fixation is a common practice among surgeons. Bacteria naturally attach to these devices, increasing the risk for wound infection, which can result in non- or malunion, additional surgical procedures and extended hospital stays. Intramedullary nail surface properties can be modified to reduce bacterial colonisation and potentially infectious complications. In the current study, a coating combining a non-fouling property with leaching chlorhexidine for orthopaedic implantation was tested. Coating stability and chlorhexidine release were evaluated in vitro. Using a rat model of intramedullary fixation and infection, the effect of the coating on microbial colonisation and fracture healing was evaluated in vivo by quantitative microbiology, micro-computed tomography, plain radiography, three-point bending and/or histology. Low dose systemic cefazolin was administered to increase the similarities to clinical practice, without overshadowing the effect of the anti-infective coating. When introduced into a contaminated wound, the non-fouling chlorhexidine-coated implant reduced the overall bacteria colonisation within the bone and on the implant, reduced the osteolysis and increased the radiographic union, confirming its potential for reducing complications in wounds at high risk of infection. However, when implanted into a sterile wound, non-union increased. Further studies are required to best optimise the anti-microbial effectiveness, while not sacrificing fracture union.

Antibiotic-loaded bone void filler accelerates healing in a femoral condylar rat model.

AIMS: Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. MATERIALS AND METHODS: Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. RESULTS: We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. CONCLUSION: This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126-31.