Treatment of Infection-Related Non-Unions with Bioactive Glass—A Promising Approach or Just Another Method of Dead Space Management?

Abstract

The treatment of infected and non-infected non-unions remains a major challenge in trauma surgery. Due to the limited availability of autologous bone grafts and the need for local anti-infective treatment, bone substitutes have been the focus of tissue engineering for years. In this context, bioactive glasses are promising, especially regarding their anti-infective potential, which could reduce the need for local and systemic treatment with conventional antibiotics. The aim of this study was to investigate the osteoinductive and osteoconductive effects, as well as the anti-infectious potential, of S53P4 using a standardized non-union model, which had not been investigated previously. Using an already established sequential animal model in infected and non-infected rat femora, we were able to investigate bioactive glass S53P4 under realistic non-union conditions regarding its osteoinductive, osteoconductive and anti-infective potential with the use of µCT scans, biomechanical testing and histological, as well as microbiological, analysis. Although S53P4 did not lead to a stable union in the non-infected or the infected setting, µCT analysis revealed an osteoinductive effect of S53P4 under non-infected conditions, which was diminished under infected conditions. The osteoconductive effect of S53P4 remained almost negligible in histological analysis, even 8 weeks after treatment. Additionally, the expected anti-infective effect could not be demonstrated. Our data suggested that S53P4 should not be used in infected non-unions, especially in those with large bone defects.

Efficacy of an Antibiotic Loaded Ceramic-Based Bone Graft Substitute for the Treatment of Infected Non-Unions

“…Staphylococcus aureus subsp. aureus ATCC ® 49,230, which is already established in various animal models, was used for in-vivo infection [ 30 , 31 , 32 , 33 ]. As previously described, the pathogen was cultured in tryptic soy broth (TSB) at 37 °C with 5% CO 2 under constant shaking (200 rpm).…”

“…This contained 1.5 × 10 8 CFU/mL and was subsequently diluted to 1 × 10 5 CFU/mL. Then, 10 μL of this bacterial suspension including 10 3 CFU was used for in vivo infection, as described below [ 30 ].…”

“…In addition, an ex vivo scan was performed at week 8 immediately after sacrifice and complete removal of soft tissue to obtain a high-resolution image at the endpoint. The detailed settings of the scans have already been described in the literature [ 30 ], as well as the parameter settings of the image reconstruction. This was performed with the SkyScan NRecon software (v.1.6.9.8, Brucker microCT, Kontich, Belgium).…”

“…Quantitative evaluation was performed using the SkyScan CTAnalyzer (v.1.13.21, Brucker microCT, Kontich, Belgium) as previously described [ 22 , 30 ].…”

“…Our research group previously established a new sequential animal model for infection-related non-unions with segmental bone defects [ 29 ]. This two-staged animal model reflects an authentic clinical situation and allows for evaluating therapeutic interventions with bone substitutes [ 30 ] for the treatment of infected non-unions, and is thereby the first evaluation of Cerament G in an animal model of infected and non-infected non-unions. The aim of this study was to evaluate Cerament G as a therapeutic option in the treatment of infected non-unions regarding its osteoinductive, osteoconductive, and anti-infective properties by means of a standardized non-union model.…”