Fracture-related infection (FRI) remains a challenging complication that imposes a heavy burden on orthopaedic trauma patients. The surgical management eradicates the local infectious focus and if necessary facilitates bone healing. Treatment success is associated with debridement of all dead and poorly vascularized tissue. However, debridement is often associated with the formation of a dead space, which provides an ideal environment for bacteria and is a potential site for recurrent infection. Dead space management is therefore of critical importance. For this reason, the use of locally delivered antimicrobials has gained attention not only for local antimicrobial activity but also for dead space management. Local antimicrobial therapy has been widely studied in periprosthetic joint infection, without addressing the specific problems of FRI. Furthermore, the literature presents a wide array of methods and guidelines with respect to the use of local antimicrobials. The present review describes the scientific evidence related to dead space management with a focus on the currently available local antimicrobial strategies in the management of FRI. LEVEL OF EVIDENCE:: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

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Evidence-Based Recommendations for Local Antimicrobial Strategies and Dead Space Management in Fracture-Related Infection.

The aim of this study was to synthesize and characterize a nano-hydroxyapatite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) and characterized both in vitro and in vivo. In vitro studies included MTT, ALP assays, and fluorescent staining of Saos-2 (human osteoblasts) and MC3T3-E1 (murine preosteoblasts) cells cultured on NC. An in vivo study divided 20 male Wistar rats into four groups: control (defect only), NC, NC + ZA, and NC + ZA + rhBMP-2. The materials were implanted in an 8.5 mm critical size defect in the calvarium for 12 weeks. Micro-CT quantitative analysis was carried out in vivo at 8 weeks and ex vivo after 12 weeks. Mineralization was highest in the NC + ZA + rhBMP-2 group (13.0 ± 2.8 mm3) compared to the NC + ZA group (9.0 ± 3.2 mm3), NC group (6.4 ± 1.9 mm3), and control group (3.4 ± 1.0 mm3) after 12 weeks. Histological and spectroscopic analysis of the defect site provided a qualitative confirmation of neo-bone, which was in agreement with the micro-CT results. In conclusion, NC can be used as a carrier for bioactive molecules, and functionalization with rhBMP-2 and ZA in low doses enhances bone regeneration.

Nano-Hydroxyapatite Bone Substitute Functionalized with Bone Active Molecules for Enhanced Cranial Bone Regeneration

Impaired healing outcomes or even non-unions after bone injury are still a highly relevant problem in the daily clinical life. Especially within an aging population, the occurrence of bone fractures increases and thus novel treatment approaches to overcome compromised bone regeneration are needed. The gold standard to treat delayed or non-healing bone injuries is still the use of autologous bone grafts to foster regeneration. Besides its successful treatment outcome, it also has disadvantages: a second surgery is needed in order to harvest the bone material and the material is highly limited. Looking into the recent literature, a multitude of different research approaches were already conducted to identify new possible strategies to treat impaired bone regeneration: application of mesenchymal stromal cells, platelet lysates, growth factors, interference in the immune system, or bone formation stimulation by ultrasound. This review gives an overview of the treatment approaches actually performed in the clinic as well as at the bench in the context of compromised bone healing. It clearly highlights the complexity of the nature of non-healing bone fractures as well as patient-dependent factors influencing the healing process.

Clinical and Research Approaches to Treat Non-union Fracture

. Aim: To evaluate the efficacy of bioglass (BAG-S53P4) in the treatment of patients with chronic osteomyelitis and compare the results with calcium sulphate antibiotic beads in one medical centre. Methods: Retrospective analysis of 25 cases. Inclusion criteria: patients diagnosed clinically and radiographically of osteomyelitis and treated surgically (Group 1: cavitary bone defects treated with bioglass and Group 2: cavitary bone defects treated with calcium sulphate antibiotic beads) during the period of 2014 and 2015 in one medical centre. Results: Patients in group 1 (bioglass treatment): total of 12 patients (11 males and 1 female) with mean age: 50 years (30-86). Average length of hospital stay was 22 days and mean follow-up time: 23 months (16-33). Mean erythrocyte sedimentation rate (ESR) and mean c-reactive protein (CRP) before surgery: 55mm/hr and 54 mg/L, respectively. Mean ESR and mean CRP in last blood exam: 18 mm/hr and 8 mg/L, respectively. There were 2 postoperative complications: seroma formation and delayed wound healing. Only 1 patient had recurrence of infection. Patients in group 2 (calcium sulphate antibiotic beads treatment): total of 13 patients (9 males and 4 females) with mean age: 48 years (17-67). Average length of hospital stay was 21 days and mean follow-up time 22 months (16-29). Mean ESR and mean CRP before surgery: 51mm/hr and 41 mg/L, respectively. Mean ESR and mean CRP in last blood test: 15 mm/hr and 11 mg/L. 2 postoperative complications were registered: chronic expanding hematoma of the muscle flap donor site and seroma formation. 1 patient had recurrence of infection. Overall, there were no differences in recurrence of infection, p=0.740 and in complication rate, p=0.672. 11 (91,7%) patients in group 1 and 12 (92,3%) patients in group 2 showed no signs of recurrence of infection both clinically and radiologically at final follow-up. The most frequent cause of osteomyelitis in group 1 was post traumatic while a postsurgical aetiology was more frequent in group 2. The distal tibia was the most common location. The most frequent pathogen isolated in both groups was methicillin sensible staphylococcus aureus. Conclusions: An advance in treatment of patients with cavitary bone defects in chronic osteomyelitis is the use of synthetic bone substitutes although current evidence is low. In this study, we demonstrate how bioglass without local antibiotics and calcium sulphate antibiotic beads are both equally effective treatment options. Overall, there were no differences between groups in mean hospital stay, complication rates and recurrence of infection.

/pdf/treatment-of-cavitary-bone-defects-in-chronic-osteomyelitis-5dnb1g1g87.pdf

Treatment of Cavitary Bone Defects in Chronic Osteomyelitis: Biogactive glass S53P4 vs. Calcium Sulphate Antibiotic Beads.

Ceramic biomaterials: Properties, state of the art and future prospectives

. Local release of antibiotic has advantages in the treatment of chronic osteomyelitis and infected fractures. The adequacy of surgical debridement is still key to successful clearance of infection but local antibiotic carriers seem to afford greater success rates by targeting the residual organisms present after debridement and delivering much higher local antibiotic concentrations compared with systemic antibiotics alone. Biodegradable ceramic carriers can be used to fill osseous defects, which reduces the dead space and provides the potential for subsequent repair of the osseous defect as they dissolve away. A dissolving ceramic antibiotic carrier also raises the possibility of single stage surgery with definitive closure and avoids the need for subsequent surgery for spacer removal. In this article we provide an overview of the properties of various biodegradable ceramics, including calcium sulphate, the calcium orthophosphate ceramics, calcium phosphate cement and polyphasic carriers. We summarise the antibiotic elution properties as investigated in previous animal studies as well as the clinical outcomes from clinical research investigating their use in the surgical management of chronic osteomyelitis. Calcium sulphate pellets have been shown to be effective in treating local infection, although newer polyphasic carriers may support greater osseous repair and reduce the risk of further fracture or the need for secondary reconstructive surgery. The use of ceramic biocomposites to deliver antibiotics together with BMPs, bisphosphonates, growth factors or living cells is under investigation and merits further study. We propose a treatment protocol, based on the Cierny-Mader classification, to help guide the appropriate selection of a suitable ceramic antibiotic carrier in the surgical treatment of chronic osteomyelitis.

https://jbji.copernicus.org/articles/2/38/2017/jbji-2-38-2017.pdf

Michael Diefenbeck

Papers

Ceramic Biocomposites as Biodegradable Antibiotic Carriers in the Treatment of Bone Infections