Protein-based Biointerfaces to Control Stem Cell Differentiation - Biointerfaces: Where Material Meets Biology - page 8

implants compared to the uncoated. Importantly, RGD-coated implants
showed less fibrous tissue around the implant, which is considered very
positive. However, a significantly higher amount of bone for RGD coated
implants was observed mostly at the interface (0-100 mm), and the difference
in bone volume between both coated and uncoated groups gradually de-
creased with distance from the surface. There were no significant differences
between both groups at a distance of 750 mm from the implant surface.
Furthermore, an increase in the mechanical fixation was also observed;
apparent shear stiffness was significantly higher for RGD-coated implants.
A similar study on the osteoconductive hydroxyapatite coating with titanium
alloy implants using the same press-fit implant model showed only a sig-
nificant increase in bone ongrowth but no difference in mechanical
fixation. 45
To immobilize RGD on amino-functionalized glass surfaces Dechantsreiter
et al. 43 suggested the use of isothiocyanate-terminated peptides. It was
demonstrated that RGD peptides were fused to an isothiocyanate anchor
during synthesis and bound to amino-terminated surfaces. Importantly, two
types of linear peptides and one cyclic peptide were investigated and were
shown to enhance cell spreading and induce the formation of focal adhesions
in murine fibroblasts. The authors also concluded that formed adhesions
were specific because cells did not recognize the corresponding negative
control peptides and did not spread in the presence of soluble H-RGDS-OH
peptide. This coupling method was shown to be effective also for patterning,
where cells selectively recognized areas coated with RGD-containing peptides.
Better integration and deposition of the bone on the surface is directly
linked to pullout strength of the implants. O'Toole suggested the use of bone
sialoproteins (BSPs) to improve the pullout strength. 46 In his approach two
scenarios were considered: (1) BSPs were coated on the surface and (2) BSPs
were not placed directly on the surface but BSP-containing gelatin was used
as a plug where the implant was placed. Results failed to demonstrate the
benefits of the BSP. In general, BSP-coated acid-etched implants perform
more poorly, mechanically, than do uncoated implants. It was concluded
that BSP forms an insulating barrier on the implant surface, preventing the
direct apposition of the bone on the implants. At the same time, histology
tests showed that the BSP coating failed at the BSP-implant interface but
osteoinductive behaviors were confirmed at the BSP-bone interface. It was
postulated that a better method of coating is required to allow the formation
of bone at the interface with the implant. Similar results were found for the
second group where BSP-containing gelatin was used. These implants per-
formed poorly both histologically and mechanically. Histologically, osteoid,
osteoblasts and osteocytes are stimulated by the presence of BSP, but it was
not observed at the surface. This distant osteoinduction does not correspond
with better mechanical performances when implants are subjected to pull-
out testing analysis.
With respect to proteins, peptides benefit from a lower immunogenic
activity as well as from the ability to be synthesized and handled.

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