title: Effects of Local Antibiotic Delivery from Porous Space Maintainers on Infection Clearance and Induction of an Osteogenic Membrane in an Infected Bone Defect.
abstract: 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.
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Sarita R
authors.initials: SR
authors.lastname: Shah
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Brandon T
authors.initials: BT
authors.lastname: Smith
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Tatara
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Molina
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Trenton C
authors.initials: TC
authors.lastname: Piepergerdes
authors.affiliation: 2 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Brent A
authors.initials: BA
authors.lastname: Uhrig
authors.affiliation: 2 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Robert E
authors.initials: RE
authors.lastname: Guldberg
authors.affiliation: 3 Department of BioSciences, Rice University , Houston, Texas.
authors.forename: George N
authors.initials: GN
authors.lastname: Bennett
authors.affiliation: 4 Extremity Trauma & Regenerative Medicine, U.S. Army Institute of Surgical Research , San Antonio, Texas.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
authors.affiliation: 1 Department of Bioengineering, Rice University , Houston, Texas.
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Mikos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D002981:Clindamycin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005264:Femoral Fractures / Q000188:drug therapy / Q000382:microbiology; D005269:Femur / Q000378:metabolism / Q000382:microbiology; D019904:Polymethyl Methacrylate / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000254:growth & development*; D014946:Wound Infection / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D019904:Polymethyl Methacrylate
keywords: PMMA; antibiotics; clindamycin; induced membrane; infection