Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge.

Implant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an in situ coupling reaction of branched poly(ethylene glycol) and poly(allyl mercaptan) (PEG-PAM) polymers to generate an amphiphilic polymeric coating. We show in vivo efficacy in preventing implant infection in both post-arthroplasty infection and post-spinal surgery infection mouse models. Our technology displays efficacy with or without systemic antibiotics, the standard of care. Our coating technology is applied in a clinically relevant time frame, does not require modification of implant manufacturing process, and does not change the implant shelf life.

Evading the host response: Staphylococcus "hiding" in cortical bone canalicular system causes increased bacterial burden.

Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this "limb salvage" surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar-canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

The Use of a Novel Antimicrobial Implant Coating In Vivo to Prevent Spinal Implant Infection.

STUDY DESIGN: A controlled, interventional animal study. OBJECTIVE: Spinal implant infection (SII) is a devastating complication. The objective of this study was to evaluate the efficacy of a novel implant coating that has both a passive antibiotic elution and an active-release mechanism triggered in the presence of bacteria, using an in vivo mouse model of SII. SUMMARY OF BACKGROUND DATA: Current methods to minimize the frequency of SII include local antibiotic therapy (vancomycin powder), betadine irrigation, silver nanoparticles, and passive release from antibiotic-loaded poly(methyl methacrylate) cement beads, all of which have notable weaknesses. A novel implant coating has been developed to address some of these limitations but has not been tested in the environment of a SII. METHODS: A biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics. The in vivo performance of this coating was tested in the delivery of either vancomycin or tigecycline in a previously established mouse model of SII. Noninvasive bioluminescence imaging was used to quantify the bacterial burden, and implant sonication was used to determine bacterial colony-forming units (CFUs) from the implant and surrounding bone and soft tissue. RESULTS: The PEG-PPS-vancomycin coating significantly lowered the infection burden from postoperative day 3 onwards (P < 0.05), whereas PEG-PPS-tigecycline only decreased the infection on postoperative day 5 to 10 (P < 0.05). CFUs were lower on PEG-PPS-vancomycin pins than PEG-PPS-tigecycline and PEG-PPS pins alone on both the implants (2.4 × 10, 8.5 × 10, and 1.0 × 10 CFUs, respectively) and surrounding bone and soft tissue (1.3 × 10, 4.8 × 10, and 5.4 × 10 CFUs, respectively) (P < 0.05). CONCLUSION: The biodegradable PEG-PPS coating demonstrates promise in decreasing bacterial burden and preventing SII. The vancomycin coating outperformed the tigecycline coating in this model compared to prior work in arthroplasty models, highlighting the uniqueness of the paraspinal infection microenvironment. LEVEL OF EVIDENCE: N/A.