Abstract
Cerament (Bonesupport Holding, Lund, Sweden) is a bioresorbable synthetic bone substitute consisting of calcium sulfate and hydroxyapatite which is successfully used as a bone graft in bone defects or in delayed and non-unions after fractures. Besides, calcium sulfate/ hydroxyapatite (CAS/HA) could have, attributed to its composition and osteoinductive properties, have great importance in the treatment of bone infections with critical size defects (CSD). Aim of the study was to evaluate the effects of antibiotic infused CAS/HA on inflammation and bone healing in an implant-associated osteitis mice model. In a standardized murine model, the left femur of 72 BALB/c mice were osteotomized, generating a CSD (2,5 mm) with stabilization through a 6-hole titanium locking plate. Osteitis has been induced through inoculation of Staphylococcus aureus (SA) into the fracture gap. To analyze the effect of CAS/HA, following groups were generated with either CAS/HA, CAS/HA with gentamycin (CAS/ HA-G) or CAS/HA with vancomycin (CAS/HA-V) insets placed into the osteotomy. Debridément and lavages were progressed on day 7 and 42 to determine the local bacterial growth and the immune reaction. Fracture healing was quantified on day 7 and 42 by x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of Interleukin (IL)– 6 and polymorphonuclear neutrophils (PMN) in lavage samples. Osteitis induced higher IL-6 and PMN-levels in the lavage samples on day 7. Both parameters showed a reduction in all groups on day 42. CAS/HA-V revealed a significant reduction of CFU and PMNs in lavage samples on day 42. A positive effect on bone healing could only be shown in non-infected mice. Whereas, application of mere CAS/HA in infected mice did show tendencies of bone destruction and lysis, independent of impregnation with antibiotics or not. Thus, application of CAS/HA in acute implant-associated infections is not recommended. In non-infectious environments or after infect-convalescence CAS/HA could albeit serve as a suggestive tool in trauma and orthopedic surgery.
Highlights
Osteitis is described as an infection of the bone with a concomitant inflammation involving the bone marrow and the surrounding tissues [1]
21 mice died during experimental procedures. 10 of these animals died peri- or postoperative, 9 of these mice were early euthanized as they met endpoint criteria (3 mice because of immobility and non-weight bearing of the operated extremity, 6 mice because of non-controllable wound defects). 2 mice were found dead in the cage with no evident reason for death. 51 mice were considered for analysis
Infection progress was verified by estimation of the numbers of colony-forming units (CFU) gained from the lavage on day 7 and 42
Summary
Osteitis is described as an infection of the bone with a concomitant inflammation involving the bone marrow and the surrounding tissues [1]. Time borders are set distinctly, from 4 to 8 weeks describing an acute event and all exceeding that characterizing a chronic process [11] Both osteitis types are addressed by surgical intervention in terms of radical debridement, lavage and removal of implants as the gold standard of therapy, combined with systemic or oral antibiotic treatment [12]. Several clinical studies have demonstrated the efficacy of antibiotic infused CAS/HA with gentamicin sulfate or vancomycin in the treatment of infected bone defects as well as the successful use as a coating on implants [16,17,18,19]. Et al for example, present the effective treatment of chronic osteomyelitis with gentamicin loaded CAS/ HA spacer in patients [19] Limitations of these studies seem to be that they either describe a primary infect
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