The Cell–Surface Interaction - Tissue Engineering: Cell-Surface Interactions for Tissue Culture - page 4

protein coating because of its higher affinity for the surface, exchanging with the
smaller and more weakly bound albumin [ 2 , 3 ].
The desirable effect upon implantation of a device is the formation of a
haematoma. This dynamic structure contains factors important in recruiting cells
essential for inflammatory-mediated response, bone repair and angiogenesis [ 4 - 7 ].
To achieve this outcome, platelets undergo the process of degranulation upon
adhering to a surface. This involves the release of intracellular contents such as
potent platelet activators, which in turn recruit additional platelets to the wound
site [ 8 , 9 ]. Macrophages and other inflammatory cells such as granulocytes,
lymphocytes and monocytes infiltrate the haematoma and function to prevent
infection and to secrete cytokines and growth factors such as fibroblast growth
factor 2, vascular endothelial factor, macrophage colony stimulating factor,
interleukins, bone morphogenetic proteins (BMPs) and tumour necrosis factor a
(see [ 5 ] for a review). Furthermore, activated platelets secrete a myriad of growth
factors, such as platelet-derived growth factor and transforming growth factor b
(TGFb). The latter factors possess chemotactic activity, thus serving as migratory
signals for repair cells such as osteoblasts, fibroblasts, monocytes, neutrophils and
leukocytes [ 10 , 11 ].
2.2 The Role of Integrins
The interactions of surface-bound proteins with cells are mediated via integrins.
These cell membrane glycoproteins recognize and bind a variety of cell-
surface-associated and extracellular matrix (ECM)-associated ligands. Integrin
receptors are heterodimers composed of a and b subunits that occur in distinct
combinations which then bind specific ligands. A subset of the a subunits have an
additional structural domain located towards the N-terminal. This is known as the
a-A domain (also termed the a-I domain). Integrins carrying this domain either
bind to collagens (e.g. integrins a 1 b 1 , and a 2 b 1 ), or act as cell-cell adhesion
molecules (integrins of the b 2 family). Integrins that do not have this inserted
domain on the a subunit do have an A-domain in their ligand binding site, which is
found on the b subunit.
In both cases, the A-domains carry up to three divalent cation binding sites. One
is permanently occupied in physiological concentrations of divalent cations, and
carries either a calcium or a magnesium ion, the principal divalent cations in blood
at median concentrations of 1.4 mM (calcium) and 0.8 mM (magnesium). The
other two sites become occupied by cations when ligands bind—at least for those
ligands involving an acidic amino acid in their interaction sites. The interaction of
integrins with ligands is based on the ability of the receptors to recognize the
arginine-glycine-aspartic acid (RGD) tripeptide sequence [ 12 ].
Osteoblasts express various integrins that bind numerous ECM ligands.
Specifically, integrins a 2 b 1 and a 5 b 1 are crucial in osteoblast function. The a 2
subunit is one of the type I collagen receptors. It also plays an important role in