BIOMIMETIC MATRICES FOR INTEGRIN-MEDIATED CELL ADHESION - Biologically-Responsive Hybrid Biomaterials - page 240

advantageous because they allow for the modulation of material surface
properties within the first few outermost molecular layers of a solid surface,
while retaining the beneficial properties of the bulk material such as
biocompatibility, degradability, and mechanical integrity [40]. Methods to
accomplish these modifications range from simple non-specific protein
adsorption [36] to more complex techniques that change the surface properties of
a material, such as hydrophilicity, charge, topology, and chemical makeup, to
enhance protein adsorption from serum or plasma [40] [Figure 3]. As reviewed
below, each technique has unique advantages and disadvantages, and varies
highly depending on the biomaterial, target protein, technique used,

physiological environment, and cell type of interest.

4.1. Physical adsorption of ECM proteins to biomaterials

Physical adsorption of ECM proteins is the oldest, easiest, and most widely used
technique to enhance the bioactivity of any material. When a foreign material
such as a polymeric film or metallic substrate is introduced into a physiological
environment, proteins such as fibronectin (FN) and vitronectin (VN) are non-
specifically and spontaneously adsorbed on the surface of the material [36,41].
As demonstrated by García et al. [42], the increasing density of a FN adsorbed
layer results in a linear increase in density of ŋ 5 Ȳ 1 integrin-FN bonds, as
predicted by simple receptor-ligand equilibrium. However, as Nikolovski et al.
[43] demonstrated, the amount of non-specific protein absorbed from serum-
containing solutions differs with material used. Results revealed that in solutions
with equal protein concentrations, VN adsorbs favorably over FN onto
polyglycolic acid (PGA), polylactic acid (PLA), and collagen 2D films and 3D
scaffolds. Further, the proteins adsorbed specifically modulate integrin
expression. The adhesion of smooth muscle cells (SMCs) is mediated by
adhesion of the α v β 5 integrin receptor to VN, the α 5 β 1 integrin receptor to FN,
and the α 2 β 1 integrin receptor to type-I collagen. This integrin expression,
however, is tunable. In a study conducted by Stephansson et al. [44], the binding
and clustering of MC3T3-E1 osteoblast-like cell α 5 β 1 integrins into focal
adhesions varied with substrate type (untreated, tissue culture, and type-I
collagen-coated polystyrene), with the greatest binding and clustering observed
on the biomimetic surface. This resulting integrin expression has been shown in
countless studies to modulate cell behavior. For instance, Chastain and
colleagues [45] showed that mesenchymal stem cell (MSC) osteogenic
differentiation was particularly enhanced with collagen-I mediated adhesion to
thin films of poly(lactic-co-glycolic acid) (PLAGA), as opposed to VN mediated