Testing of a bioactive, moldable bone graft substitute in an infected, critically sized segmental defect model

Large infected bone defects, often resulting from high energy traumas, are difficult to treat due to their variability in complexity and location. Standard treatment for infected bone defects begins with a protocol that includes a series of debridements in conjunction with an extended course of systemic antibiotics. Only after the infection has been eliminated will repair of the defect commence, typically with implantation of autologous bone. To address some of the shortcomings of the standard treatment methods, such as serial procedures, limited grafting material, and the need for a second surgical site for autologous bone, a sequential, dual drug-releasing, moldable, calcium sulfate-based bone graft substitute was developed previously. In the present studies, the effectiveness of the material for treating both the infection with vancomycin and bone defect with simvastatin was evaluated in vivo using a critically sized, infected segmental defect model in rat femurs. Although the infection was not fully eliminated, the local release of vancomycin increased survivorship of infected animals by 464% compared to nontreated controls. Infected animals receiving antimicrobial treatment showed comparable amounts of new bone formation within the defect site when compared to noninfected controls. Incorporating agents capable of disrupting established biofilms into bone graft substitutes may enhance effectiveness in treating a biofilm infection within a bone defect.