Polymethylmethacrylate (PMMA) also referred as (acrylic) bone cement is a non-degradable biomaterial that has been used in clinical orthopedic practice for several decades. PMMA can be used in a plain formulation, but is often used in an antibiotic-loaded formulation in (primary and revision) arthroplasty and in treatment of orthopedic infections as prosthetic joint infections (PJI) and chronic osteomyelitis. In treatment of PJIs antibiotic-loaded PMMA is often used as a carrier material for local antibiotic delivery in addition to treatment with systemic antibiotics. In this case, the antibiotic-loaded PMMA is often used as a spacer or as a bead chain. Since the introduction of PMMA as an antibiotic carrier there is a tremendous amount of scientific and clinical papers published, which studied numerous different aspects of antibiotic-loaded PMMA. This paper will review the research regarding basic principles of antibiotic-loaded PMMA as mechanism of action, antibiotic-release capacities, choice of antibiotics and influences on mechanical properties of PMMA. Subsequently, concerns regarding the application of antibiotic-loaded PMMA, biofilm formation, antibiotic resistance and local or systemic toxicity will be discussed. In addition to these subjects, the role of antibiotic loaded PMMA in clinical treatment of PJIs and chronic osteomyelitis is discussed in the final part of this paper.

Osteomyelitis is a common occurrence in orthopaedic surgery, which is caused by different bacteria. Treatment of osteomyelitis patients aims to eradicate infection by debridement surgery and local and systemic antibiotic therapy. Local treatment increases success rates and can be performed with different antimicrobial bone graft substitutes. This review is performed to assess the level of evidence of synthetic bone graft substitutes in osteomyelitis treatment. According to the PRISMA statement for reporting systematic reviews, different types of clinical studies concerning treatment of osteomyelitis with bone graft substitutes are included. These studies are assessed on their methodological quality as level of evidence and bias and their clinical outcomes as eradication of infection. In the fifteen included studies, the levels of evidence were weak and in ten out of the fifteen studies there was a moderate to high risk of bias. However, first results of the eradication of infection in these studies showed promising results with their relatively high success rates and low complication rates. Due to the low levels of evidence and high risks of bias of the included studies, these results are inconclusive and no conclusions regarding the performed clinical studies of osteomyelitis treatment with antimicrobial bone graft substitutes can be drawn.

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Chronic osteomyelitis has always been a therapeutic challenge for patient and surgeon due to the specific problems related with bone infection and bacterial biofilm eradication. Other than being the cause of infection or facilitating spread or persistence of infection, biomaterials are also becoming a tool in the treatment of infection. Certain novel biomaterials have unique and ideal properties that render them perfectly suited to combat infection and are therefore used more and more in the treatment of chronic bone infections. In case of infection treatment, there is still debate whether these properties should be focused on bone regeneration and/or their antimicrobial properties. These properties will be of even greater importance with the challenge of emerging antimicrobial resistance. This review highlights indications for use and specific material properties of some commonly used contemporary biomaterials for this indication as well as clinical experience and a literature overview.

Introduction: Treatment of infected non-unions of the tibia is a challenging problem. The cornerstones of optimal infected non-union treatment consist of extensive debridement, fracture fixation, antimicrobial therapy and creation of an optimal local biological bone healing environment. The combination of S53P4 bioactive glass (BAG), as osteostimulative antibacterial bone graft substitute, and bone marrow aspirate concentrate (BMAC) for the implantation of mesenchymal stem cells and growth factors might be a promising combination. In this paper, preliminary results of a new treatment algorithm for infected non-unions of the tibia is presented.Methods: In this retrospective case series patients with infected non-unions of the tibia are treated according to a new treatment algorithm. Patients are treated with extensive debridement surgery, replacement of the osteosynthesis and implantation of S53P4 BAG and BMAC in a one-stage or two-stage procedure based on non-union severity. Subsequently patients are treated with culture based antibiotic therapy and followed until union and infection eradication.Results: Five patients with an infected non-union were treated, mean age was 55, average NUSS-score was 44 and the average segmental bone defect was 4.6cm. One patient was treated in a one-stage procedure and four patients in a two-stage induced membrane-, or "Masquelet"-procedure. On average, 23 ml S53P4 BAG and 6.2 ml BMAC was implanted. The mean follow-up period was 13.6 months and at the end of follow-up all patients had clinical consolidation with an average RUST-score of 7.8 and complete eradication of infection.Discussion: These early data on the combined implantation of S53P4 BAG and BMAC in treatment of infected non-unions shows promising results. These fracture healing results and eradication rates resulted in promising functional recovery of the patients. To substantiate these results, larger and higher quality studies should be performed.