title: Sequential release kinetics of two (gentamicin and BMP-2) or three (gentamicin, IGF-I and BMP-2) substances from a one-component polymeric coating on implants.
abstract: The local application of antibiotics in combination with timely controlled growth factor delivery might be beneficial for the prevention of infections and to stimulate bone healing. Therefore, in this study a variable sequential drug delivery system with three distinctly different release profiles was developed: i) a burst release of gentamicin, ii) a burst release of IGF-I followed by a sustained release, and iii) a slow sustained release of BMP-2 out of an implant coating. Only one polymer [poly(D,L-lactide)], incorporating gentamicin, IGF-I or BMP-2, was used for two- or three-layer coatings of K-wires. To control the release kinetics, the polymer concentrations in the solvent were varied. The activity of early released gentamicin from a two-layer coating was confirmed microbiologically and BMP-2 stimulated the metabolic activity and alkaline phosphatase activity of C2C12 cells after 2 weeks. From the three-layer coated wires, IGF-I continuously stimulated the cell proliferation, whereas BMP-2 enhanced ALP between 1 and 3 weeks. The sequential release of growth factors revealed an additive effect on the metabolic activity and ALP of primary osteoblast-like cells compared to the single coated controls. The controlled delivery of different factors from one implant might prevent infections and subsequently stimulate the different phases of bone healing.
authors.affiliation: Julius Wolff Institute, Center for Musculoskeletal Surgery, Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany. catrin.strobel@charite.de
authors.forename: Catrin
authors.initials: C
authors.lastname: Strobel
authors.forename: Nicole
authors.initials: N
authors.lastname: Bormann
authors.forename: Anke
authors.initials: A
authors.lastname: Kadow-Romacker
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmidmaier
authors.forename: Britt
authors.initials: B
authors.lastname: Wildemann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D001864:Bone Wires / Q000382:microbiology; D018929:Cell Culture Techniques; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000379:methods; D005839:Gentamicins / Q000008:administration & dosage*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007700:Kinetics; D051379:Mice; D008855:Microscopy, Electron, Scanning; D032446:Myoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D004338:Drug Combinations; D005839:Gentamicins; D011091:Polyesters; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I; D010744:Phosphoric Monoester Hydrolases