The Cell–Surface Interaction - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 10

Many recent studies have demonstrated a significant impact of RGD sequence-
integrin receptor interactions on osteoblast adhesion, migration, gene and protein
expression and mineralization [ 51 ]. Results obtained by Zreiqat et al. [ 51 ] showed
that modifying TAV surfaces with RGD peptide upregulated bone protein levels of
osteocalcin, type I collagen and bone sialoprotein at 7 days, compared with control
surfaces, such as coated a control peptide RGE and a control amino acid surface
bound with cysteine. Additionally, alkaline phosphatase production on RGD-
modified TAV was significantly higher at day 14 on the RGD surface compared
with the control surfaces. These results indicate that the implant surfaces modified
with RGD peptide regulate and promote bone formation and calcification in vitro.
Rammelt et al. [ 52 ] compared different organic coatings to assess their influ-
ence on bone remodelling and healing. Briefly, in their study titanium implants
coated with collagen type I, RGD peptides and chondroitin sulphate were
implanted into the tibia of rat. The histological and immunohistochemical evalu-
ation of the effect of RGD on bone remodelling at the implant surface revealed that
the addition of RGD proteins enhances bone healing and direct bone contact with
the implant surface after 4 weeks. Furthermore, the RGD sequence directly acti-
vates macrophages, osteoblasts and osteoclasts, which results in faster bone
remodelling activity around titanium implants. This leads to earlier transformation
of the newly formed woven bone into lamellar bone around day 14.
Titanium surfaces may also be coated with the more selective collagen-
mimetic peptide glycine-phenylalanine-hydroxyproline-glycine-glutamine-arginine
(GFOGER). It was shown that this sequence selectively promotes binding of a 2 b 1
integrin [ 53 ], a crucial receptor for osteoblast differentiation that interacts with type I
collagen to activate the Runx2 transcription factor to regulate osteoblast differenti-
ation [ 13 ]. Reyes et al. [ 43 ] showed significantly higher osteoblast-specific gene
expression, such as expression of Runx2 transcription factor, osteocalcin and bone
sialoprotein, in rat bone marrow stromal cells for samples treated with GFOGER
peptide compared with uncoated samples. Additionally, enhanced implant-
osteoblast contact in vitro was observed together with increased alkaline phosphatase
activity and calcium content on coated titanium and confirmed the positive effect on
osteoblastic differentiation. Also, the GFOGER peptide coating influenced and
enhanced osseointegration of titanium implants in vivo. However, although
these results are promising; they were obtained from a rat model system. Thus,
further studies focusing on the evaluation of the response of human osteoblasts to
GFOGER-coated implants would give more clinically relevant results.
BMPs are a group of growth factors belonging to the TGFb superfamily that
have prominent roles in a variety of bone-related processes, one of which includes
osteoblast differentiation. Moreover, several BMPs, in particular BMP-2, have
been shown to be involved in the substrate-dependent cell reponse [ 54 ]. BMP-2-
coated TiO 2 nanotubes of various diameters have also been shown to induce
significantly increased levels of osteoblast differentiation in MSCs in vitro [ 55 ].
However, understandably, biological modification requires an appreciation of the
type, delivery and concentration of the biomolecule to be used as several studies
have reported conflicting results when evaluating implant surfaces modified by