title: RGDS peptides immobilized on titanium alloy stimulate bone cell attachment, differentiation and confer resistance to apoptosis.
abstract: A major cause of implant failure in skeletal tissues is failure of osseointegration, often due to lack of adhesion of cells to the titanium (Ti) alloy interface. Since arginine-glycine-aspartic acid (RGD)-containing peptides have been shown to regulate osteoblast adhesion, we tested the hypothesis that, bound to a Ti surface, these peptides would promote osteoblasts differentiation, while at the same time inhibit apoptosis. RGDS and RGES (control) peptides were covalently linked to Ti discs using an APTS linker. While the grafting of both RGDS and RGES significantly increased Ti surface roughness, contact angle analysis showed that APTS significantly increased the surface hydrophobicity; when the peptides were tethered to Ti, this was reduced. To evaluate attachment, MC3T3-E1 osteoblast cells were grown on these discs. Significantly more cells attached to the Ti-grafted RGDS then the Ti-grafted RGES control. Furthermore, expression of the osteoblasts phenotype was significantly enhanced on the Ti-grafted RGDS surface. When cells attached to the Ti-grafted RGDS were challenged with staurosporine, an apoptogen, there was significant inhibition of apoptosis; in contrast, osteoblasts adherent to the Ti-grafted RGES were killed. It is concluded that RGD-containing peptides covalently bonded to Ti promotes osteoblasts attachment and survival with minimal changes to the surface of the alloy. Therefore, such modifications to Ti would have the potential to promote osseointegration in vivo.
authors.affiliation: Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Secchi
authors.forename: V
authors.initials: V
authors.lastname: Grigoriou
authors.forename: I M
authors.initials: IM
authors.lastname: Shapiro
authors.forename: E A
authors.initials: EA
authors.lastname: Cavalcanti-Adam
authors.forename: R J
authors.initials: RJ
authors.lastname: Composto
authors.forename: P
authors.initials: P
authors.lastname: Ducheyne
authors.forename: C S
authors.initials: CS
authors.lastname: Adams
mesh_terms: D000497:Alloys; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D020099:Coated Materials, Biocompatible; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides; D010006:Osteoblasts / Q000648:ultrastructure*; D013499:Surface Properties; D014025:Titanium
chemical_list: D000497:Alloys; D020099:Coated Materials, Biocompatible; D009842:Oligopeptides; C046617:arginyl-glycyl-aspartyl-serine; D014025:Titanium