Differentiation of human bone‐derived cells grown on GRGDSP‐peptide bound titanium surfaces

Abstract

Various surface modifications have been applied to titanium alloy (Ti-6Al-4V) implants, in an attempt to enhance osseointegration; crucial for ideal prosthetic fixation. Despite the numerous studies demonstrating that peptide-modified surfaces influence in vitro cellular behavior, there is relatively little data reporting their effects on bone remodeling. The objective of this article was to examine the effects of chemically modifying Ti-6Al-4V surfaces with a common RGD sequence, a 15-residue peptide containing GRGDSP (glycine-arginine-glycine-aspartate-serine-proline), on the modulation of bone remodeling. The expression of proteins known to be associated with osseous matrix and bone resorption were studied during the growth of human bone-derived cells (HBDC) on these peptide-modified surfaces. HBDC grown for 7 days on RGD surfaces displayed significantly increased levels of osteocalcin, and pro-collagen Ialpha1 mRNAs, compared with the production by HBDC grown on the native Ti-6Al-4V. A pattern that was also reflected at the protein levels for osteocalcin, type I collagen, and bone sialoprotein. Moreover, HBDC grown for 7 and 14 days on RGD-modified Ti-6Al-4V expressed significantly higher level of osteoclast differentiation factors and lower levels of osteoprotegerin and IL-6 proteins compared with other surfaces tested. These results suggest that different chemical treatments of implant material (Ti-6Al-4V) surface result in differential bone responses, not only their ability to form bone but also to stimulate osteoclastic formation.

Gene expression monitoring in osteoblasts on titanium coated with fibronectin-derived peptide

“…Studies have shown that RGD and related peptides are able to enhance osteoblast adhesion and migration 11,12) . Zreiqat et al 8) reported that human bone-derived cells on GRGDSP peptide-bound Ti surfaces displayed significantly increased levels of OC gene expression when compared to uncoated Ti. Furthermore, Ferris et al 6) found that RGD-coated Ti implants stimulated new bone formation in vivo, such that there was a significant increase in bone volume around Ti implants in rat femur after implantation.…”

“…It was found that the GRGDSP peptide derived from FN had the highest cell attachment activity among these peptides tested 7) . In a separate study, Zreiqat et al 8) reported that cells derived from human bone cultured on GRGDSP peptide-bound Ti surfaces displayed significantly increased level of osteocalcin (OC) gene expression when compared to uncoated Ti. By means of an in vivo animal study, significantly improved mechanical fixation and increased bone formation were achieved around Ti implants coated with RGD peptides and implanted into the femoral condyles of dogs 9) .…”

Impact of Biomimetic Diamond-like Carbon coated Titanium on Osteoblast and Osteoclast Differentiation in vitro

“…At present, several methods have developed implant surface modifications to improve implant treatment [15][16][17][18][19][20], including antimicrobial peptide [15,16], RGD peptide [17,18] and recombinant bone morphogenetic protein (BMP)-2 [19,20]. Taking advantage of the biocompatible characteristics of the titanium surface, we also have attempted surface modifications using biomimetic DLC coated technique [11,12].…”

Biochemical modification of titanium surfaces: Peptides and eCM proteins

“…Interestingly, osteoblasts on RGDC surfaces showed osteocalcin (OC) mRNA expression at day 15, that is significantly earlier as compared with controls: osteoblasts on Ti and RDGCcoated surfaces began to show OC mRNA expression just at day 21, providing evidence of the enhanced functions of osteoblasts cultured on the RGDC-modified surfaces. Zreiqat et al (2003) presented a very interesting paper that not only discusses the effect of surface-tethered RGD peptides on bone cells adhesion and differentiation, but also on bone remodelling. Briefly, a thirteen amino-acid RGD peptide Gly-Arg-Gly-Asp-Ser-Pro-Tyr-Gly-GlyGly-Gly-Gly-Cys (GRGDSPYGGGGGC) was linked to Ti-6Al-4V (Ti grade 5) surfaces aminated by silane chemistry, through the thiol on the cysteine residue and a maleimide coupler.…”