Reconstruction of large bone defects can be complicated by the presence of both
infection and local
antibiotic administration. This can be addressed through a two-stage reconstructive approach, called the Masquelet technique, that involves the generation of an induced osteogenic membrane over a temporary
poly(methyl methacrylate) (
PMMA) space maintainer, followed by definitive reconstruction after the induced membrane is formed. Given that
infection and
antibiotic delivery each have independent effects on local tissue response, the objective of this study is to evaluate the interaction between local
clindamycin release and bacterial contamination with regards to
infection prevention and the restoration of pro-osteogenic gene expression in the induced membrane. Porous
PMMA space maintainers with or without
clindamycin were implanted in an 8 mm rat femoral defect model with or without Staphylococcus aureus inoculation for 28 days in a full-factorial study design (four groups, n = 8/group). Culture results demonstrated that 8/8 animals in the inoculated/no
antibiotic group were infected at 4 weeks, which was significantly reduced to 1/8 animals in the inoculated/
antibiotic group. Quantitative polymerase chain reaction analysis demonstrated that
clindamycin treatment restores inflammatory
cytokine and
growth factor expression to the same levels as the no inoculation/no
antibiotic group, demonstrating that
clindamycin can ameliorate the negative effects of bacterial inoculation and does not itself negatively impact the expression of important
cytokines. Main effect analysis shows that bacterial inoculation and
clindamycin treatment have independent and interacting effects on the gene expression profile of the induced membrane, further highlighting that
antibiotics play an important role in the regeneration of infected defects apart from their antimicrobial properties.