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. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1878-1886, 2018.

Temporal separation in the release of bioactive molecules from a moldable calcium sulfate bone graft substitute.

Treatment of infected bone defects presents a considerable challenge due to the complications that occur from significant bone damage concomitant with contaminated tissue. These wounds are most often treated in a two-step sequence, where the infection is first eliminated before any attempt to repair the bone is undertaken. In order to combine these two treatment steps into one procedure, a moldable bone grafting material was developed to deliver drugs in a temporally separated manner. This was accomplished by a two-layered calcium sulfate composite consisting of a moldable outer shell containing antibiotic-loaded poly(lactic-co-glycolic acid) microspheres wrapped around a preformed core containing an osteogenic drug. The release of vancomycin from the shell portion began immediately and continued over the course of 6 weeks, while the release of simvastatin from the core was delayed for 12 days before being released over the next 4 weeks. Bioactivity of vancomycin was shown in modified Kirby-Bauer experiments in which whole samples inhibited Staphylococcus aureus (S. aureus) growth for 2 weeks. This two-layered system is capable of delivering antibiotics locally for clinically relevant periods of time and delaying the release of osteogenic drugs to mimic a two-step procedure that has potential for treating infected bone defects.