Assessment of a novel matrix as a delivery device for antimicrobials and bone morphogenetic protein-2
dc.contributor.author | Rousseau, Marjolaine | |
dc.date.accessioned | 2011-01-12T19:16:19Z | |
dc.date.available | 2011-01-12T19:16:19Z | |
dc.date.graduationmonth | May | en_US |
dc.date.issued | 2011-01-12 | |
dc.date.published | 2011 | en_US |
dc.description.abstract | Drug delivery systems for time release of recombinant human bone morphogenetic protein-2 (rhBMP-2) and antibiotics in orthopedic surgeries continue to be developed. Recently, a biodegradable novel polymeric matrix has been developed for this purpose. We hypothesized that impregnation of the matrix with rhBMP-2 would enhance bone healing. The objectives of the study were to characterize elution of rhBMP-2 and two antimicrobials (tigecycline, tobramycin) from the matrix, and bone response to the matrix in the presence or absence of rhBMP-2 and antimicrobials. In vitro elution of tigecycline, tobramycin, and rhBMP-2 from the matrix was investigated. Drug concentration in media were measured on days 1-6, 8, 10, 13, 15, 17, 21, 25, 28, and 30 using high pressure liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS; antimicrobials) and ELISA (rhBMP-2). In vivo testing was done using a unicortical defect created into each tibia of twenty adult goats. Animals were randomly assigned to one of 5 groups: 1) control (untreated defect); 2) matrix; 3) matrix+ antimicrobials (tigecycline+tobramycin); 4) matrix+rhBMP-2; and 5) matrix+antimicrobials+rhBMP-2. Plasma concentration of tigecycline and tobramycin and serum concentration of rhBMP-2 were measured by the above techniques on days 1-7, 9, 11, 13, 15, 17, 22, 26, and 30. Bone response was assessed on days 0, 14, and 30 using radiographic scoring and dual energy X-ray absorptiometry (bone mineral density [BMD]). After euthanasia on day 30, histomorphologic analyses of the bone defects were done. Categorical variables were analyzed using a generalized linear model, and continuous variables using an ANOVA with P < 0.05 considered significant. In vitro elution was characterized by a rapid release on day 1 followed by a slow release until day 30 for both antimicrobials and rhBMP-2. Plasma antimicrobial concentrations showed continued release throughout the study period. Serum rhBMP-2 concentration, radiographic scores and BMD were not significantly different between groups. Periosteal and endosteal reaction surface areas were significantly greater surrounding the defects in group 4 (matrix+rhBMP-2). There was no significant difference between the groups for the percent of bone filling the defect. The matrix served as an appropriate antimicrobial and rhBMP-2 delivery system and successfully stimulated bone production when rhBMP-2 was present. | en_US |
dc.description.advisor | David E. Anderson | en_US |
dc.description.degree | Master of Science | en_US |
dc.description.department | Department of Clinical Sciences | en_US |
dc.description.level | Masters | en_US |
dc.description.sponsorship | Kansas City Area Life Sciences Institute, Inc.; Orlumet, LLC. | en_US |
dc.identifier.uri | http://hdl.handle.net/2097/7072 | |
dc.language.iso | en_US | en_US |
dc.publisher | Kansas State University | en |
dc.subject | Drug carrier | en_US |
dc.subject | Bone healing | en_US |
dc.subject | Bone morphogenetic protein-2 | en_US |
dc.subject | Tigecycline | en_US |
dc.subject | Tobramycin | en_US |
dc.subject | Caprine fracture model | en_US |
dc.subject.umi | Biology, Veterinary Science (0778) | en_US |
dc.subject.umi | Health Sciences, Medicine and Surgery (0564) | en_US |
dc.title | Assessment of a novel matrix as a delivery device for antimicrobials and bone morphogenetic protein-2 | en_US |
dc.type | Thesis | en_US |