Protein-based Biointerfaces to Control Stem Cell Differentiation - Biointerfaces: Where Material Meets Biology - page 5

tissues. Hence, by a careful selection of the material it is possible to
stimulate cellular responses through the structural and chemical com-
position, and also to guide the adsorption of desired biomolecules that
stimulates biological responses, e.g., adsorption of cell adhesive proteins to
hydroxyapatite. 2,3

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1.1.2 Influence of Modified Surfaces on Cell Adhesion
The communication of cells with surfaces is mediated by pre-adsorbed
protein layers. The composition of this layer is critical to obtain specific
responses such as cell adhesion/repulsion, or differentiation. It is well es-
tablished that specific proteins, peptides, growth factors and drugs can
stimulate cells. 5-10 These biomolecules are used to enhance the implant
integration and also treat some dysfunction/diseases when released from
the surface. 11-13 The most common approach to enhance cell adhesion to
the surface of implantable materials using biomolecules is to incorporate
the cell binding motif Arg-Gly-Asp (RGD). 13-15 RGD, together with the
integrins that serve as receptors for them, constitute a primary recognition
system for cell adhesion. The RGD sequence is the cell attachment site of
many adhesive extracellular matrix, blood, and cell surface proteins, and
nearly half of the over 20 known integrins recognize this sequence in their
adhesion protein ligands. 16 The integrin-binding activity of adhesion pro-
teins can be achieved by engineering short synthetic peptides that contain
the RGD sequence. Interestingly, it was reported that such peptides promote
cell adhesion when immobilized onto a surface, and inhibit it when pre-
sented to cells in solution. 16 Importantly, integrin-mediated cell attachment
regulates further cell migration, growth, differentiation, and apoptosis. 14,15
The ability to target cell adhesion receptors, which are responsible not only
for cell-matrix adhesion but also for signaling bidirectionally across the cell
membrane, provides an opportunity to design new drugs (Figure 1.1). Be-
cause integrins are involved in many biological processes such as angio-
genesis, thrombosis, inflammation, osteoporosis and cancer, these drugs,
which are based on the RGD structure, can be used for the treatment of
diseases such as thrombosis, osteoporosis and cancer 17-20 (Figure 1.1).
It is well established that tethering of protein and peptides facilitates
communication with the cell. In fact, adhesion of cells is a prerequisite for
the subsequent proliferation and differentiation of cells. 7,21 Recent studies
by Webster demonstrated that adsorbed proteins including fibronectin,
laminin and vitronectin play an important role in limiting bacteria colon-
ization. 22 Hence fibronectin-functionalized surfaces can be considered as
multi-functional with a dual purpose: preventing bacteria adhesion and
enhancing cell adhesion.
While fibronectin and vitronectin receive the most attention to enhance
cell adhesion to surfaces of biomaterials, there are several types of proteins
and peptides that have been attempted to use for the same purpose. The use
of fibronectin and vitronectin is primarily dictated by their composition, in

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