title: IGF-I and TGF-beta 1 incorporated in a poly(D,L-lactide) implant coating maintain their activity over long-term storage-cell culture studies on primary human osteoblast-like cells.
abstract: Biodegradable coating of osteosynthetic materials with poly(D,L-lactide) (PDLLA) and incorporated growth factors has been used successfully as drug carrier to stimulate fracture healing in several rat and porcine models. A cold coating technique was used to incorporate growth factors without loss of activity during the coating process. The aim of this study was to investigate the activity of incorporated insulin like growth factor-I and transforming growth factor-beta 1 (TGF-beta1) after long-time storage (5 and 14 months at -20 degrees C). Primary human osteoblast-like cells (HOB) were cultured in a non-contact manner with titanium wires coated with PDLLA and IGF-I (33 microg) and TGF-beta1 (6 microg) for 0, 5, 10 and 15 days. Osteoblast culture without wires, with titanium wires or wires with the PDLLA coating served as control ( n=3 each time point and group). Cell vitality, cell proliferation and the production of procollagen 1 were measured. No differences in cell count and vitality were accessed in the two growth factor treated groups compared to the control groups at the same time point. Independently from the storage duration, the incorporated growth factors significantly stimulated the production of osteoblast specific type I collagen (CICP) compared to the controls. The results indicate, that the growth factors stimulated osteoblast to an enhanced collagen 1 production and that the coating method meets a major requirement for clinical use of growth factor-coated implants: biological activity of the incorporated growth factors for at least 14 months.
authors.affiliation: Department of Trauma and Reconstructive Surgery, Charité-Campus Virchow, Humboldt-University of Berlin, Augustenburger Platz 1, Berlin 13353, Germany. britt.wildemann@charite.de
authors.forename: B
authors.initials: B
authors.lastname: Wildemann
authors.forename: M
authors.initials: M
authors.lastname: Lübberstedt
authors.forename: N P
authors.initials: NP
authors.lastname: Haas
authors.forename: M
authors.initials: M
authors.lastname: Raschke
authors.forename: G
authors.initials: G
authors.lastname: Schmidmaier
mesh_terms: D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D024042:Collagen Type I / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D004356:Drug Storage; D017102:Fracture Healing / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry* / Q000494:pharmacology*; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011091:Polyesters / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D004343:Drug Implants; D011091:Polyesters; D016212:Transforming Growth Factor beta; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I