BIOMIMETIC MATRICES FOR INTEGRIN-MEDIATED CELL ADHESION - Biologically-Responsive Hybrid Biomaterials - page 237

such, we will look at various physical and chemical immobilization schemes
used to modify biomaterial surfaces with biologically active ECM-derived
molecules for directed cell and tissue responses. In addition, we will discuss how
bioactive ceramics have been shown to enhance favorable cell responses, such as
bone mineralization, in tissue engineered biomimetic implants.
2. Integrin-mediated Cell Adhesion
Integrins, a family of glycoprotein heterodimers, are transmembrane cell surface
adhesion receptors that represent a major pathway used by virtually all cell types
to interact with different extracellular matrix components [6]. Integrins play a
central role in the development, organization, maintenance and repair of various
tissues by providing anchorage and triggering signals that direct cell survival,
migration, cell cycle progression, and expression of differentiated phenotypes
[7]. Integrins also play a crucial role in immune and inflammatory responses
[8-10]. Each integrin is comprised of a large α-subunit containing several cation-
binding sites and a smaller Ȳ -subunit. There are over 18 α- and 8 Ȳ -subunits,
which non-covalently assemble together in the presence of extracellular calcium
to form at least 24 distinct integrin units [11] [Figure 1]. Broadly defined by their
β-subunit, the composition of the α Ȳ heterodimer determines the specificity of
the integrin towards various ECM protein ligands. Some of the heterodimer
combinations are highly specific, while others demonstrate promiscuity toward
multiple ECM ligands. Accordingly, many ECM proteins serve as ligands for
several integrin molecules [12]. Thus, the binding of integrins to their ligand is
not one-to-one and varies within cell type, local environment and material
substrate. This interaction is also affected by the conformation (section 4.1),
concentration, and spatial distribution (section 5.2) of the ligand to which the
integrin binds.
3. Cellular Adhesion to Implanted Biomaterials
In native tissues, the ECM serves many functions, including providing physical
support for cell anchorage and regulating cellular behavior. The ECM is a
complex structural entity composed of structural fibrillar proteins (collagen,
elastin); amorphous, high-molecular weight interfibrillar proteoglycans; and
specialized proteins (fibronectin, laminin, growth factors). The type, amount, and
composition of the ECM is diverse in nature, varies by tissue type, and gives
tissues their unique physical, structural and biological properties [25,26].
Resident cells interact with their surrounding ECM through a process of