IGF-I and TGF-beta 1 incorporated in a poly(D,L-lactide) implant coating stimulates osteoblast differentiation and collagen-1 production but reduces osteoblast proliferation in cell culture.
Previous in vivo studies revealed a stimulating effect of locally applied IGF-I and TGF-beta1 released from poly(D,L-lactide)-coated titanium implants on rat and porcine fracture healing. The purpose of the present study was to evaluate the effect of IGF-I (5% w/w) and TGF-beta1 (1% w/w) and the carrier PDLLA on osteoblasts in cell culture to improve the understanding of these growth factors. The well-characterized human osteoblast cell line hFOB 1.19 was used in the study. The implants and cells were cocultured in a noncontact manner. The cells were incubated for 10 days in total, and the implants (n = 6 each group and time point) were added for 1 h, 12 h, 24 h, 2 d, 4 d, or 10 d. To analyze a possible effect of the growth factors or the coating, cell proliferation, metabolism, and differentiation were investigated. As an indicator for differentiation the production of collagen I was chosen. All experimental groups showed comparable cell vitality. No change in the pH of the medium was detectable between the analyzed groups. When the effect of the titanium implant and the PDLLA coating were compared with the control culture, no differences in proliferation, metabolic activity, and collagen I production were detectable. The osteoblasts treated with IGF-I and TGF-beta1 released from PDLLA revealed a significantly enhanced collagen I production with a decrease in proliferation and metabolic activity compared to the other groups. No significant differences in collagen I production were seen due to the incubation time points. None of the experimental groups evoked an immunological response on mouse macrophages. In conclusion, the PDLLA-carrier showed no negative effect on osteoblasts, whereas the incorporated growth factors stimulated osteoblast differentiation.
Schmidmaier
G
G
Department of Trauma and Reconstructive Surgery, Charité, Campus Virchow, Humboldt-University of Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. gerhard.schmidmaier@charite.de
Wildemann
B
B
Lübberstedt
M
M
Haas
N P
NP
Raschke
M
M
D018786:Bone Substitutes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D024042:Collagen Type I / Q000096:biosynthesis; D016503:Drug Delivery Systems; D006801:Humans; D007111:Immunity, Cellular; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D011091:Polyesters; D019736:Prostheses and Implants; D014025:Titanium; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D018786:Bone Substitutes; D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D011091:Polyesters; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033616:poly(lactide); D007334:Insulin-Like Growth Factor I; D014025:Titanium