Protein-based Biointerfaces to Control Stem Cell Differentiation - Biointerfaces: Where Material Meets Biology - page 9

In addition, over the last decade, highly active and a n b 3 - and a n b 5 -integrin
selective cyclic pentapeptide ligands such as cyclo(-RGDfX) have been de-
veloped. 13 It was thus demonstrated that in addition to the RGD binding
sequence a D -amino acid, especially D -Phe following the Asp residue in the
cycle, is essential for high activities and a n selectivity. Cyclic pentapeptides
with D -amino acid in other positions and/or a non-hydrophobic amino acid
following Asp as well as linear peptides have lower activity and are less
selective towards a n integrins. Our results clarify that osteoprogenitor cells
exhibit a differential binding to RGD peptides displaying a specific con-
formation (linear RGDC and cyclo-DfKRG). Such a behavior has to be related
to the different signal transduction pathways implied by both peptides. In-
deed, some of us 14 have shown that linear GRGDSPC peptide interacts
preferentially with a w b 1 integrins while cyclo-DfKRG peptide interacts with
a n b 3 and a n b 5 integrins. Consequently, different cell adhesion at 24 h
seeding may be linked to the different cellular activity, as extracellular pro-
teins synthesis, implied by the signal transduction pathways that both RGD-
containing peptides induce, respectively. In addition, cell adhesion behavior
has to be related to the accessibility of integrins receptors by peptides dis-
playing conformation. However, both cyclo-DfKRG and linear RGDC appear
to be good candidates for developing hybrid biomaterials made of titanium
alloys and human osteogenic cells.

d n 3 r 4 n g | 1

.

1.1.3 Influence of Modified Surfaces on Cell Proliferation
and Differentiation
Besides the improvement of cell adhesion by means of adhesive proteins or
peptides, huge efforts are currently directed toward the development of
osteoconductive/osteoinductive materials. Osteo-conductive materials are
able to enhance the formation of new bone, i.e., accelerating the bone de-
velopment or improving it from a physiological point of view. Osteo-
inductive materials trigger the osteogenic process without external stimuli
(e.g., supplements in osteogenic media) and are therefore more promising
for a rapid healing process. To assess these properties in vitro, stem cells are
commonly cultured in basal and osteogenic medium and several markers of
differentiation are evaluated. For in vivo studies, they are tested by im-
plantation in ectopic and orthotopic bone site and assessing the bone for-
mation. Several directions can be followed for obtaining an osteoinductive
material. Few research groups have successfully modified the physical and
chemical properties of an inert material, such as composition, elasticity and
topography, in order to provide the inert material with osteoinductive cap-
abilities. 47-56 Another approach is based on the delivery of biomolecules,
mainly growth factors, integrated into the scaffold and able to control
osteogenesis, bone tissue regeneration and ECM formation through specific
cellular pathways in the implant site. 57 For example, insulin-like growth
factors (IGFs) and transforming growth factor-b (TGF-b) affect the migration