BIOMIMETIC MATRICES FOR INTEGRIN-MEDIATED CELL ADHESION - Biologically-Responsive Hybrid Biomaterials - page 249

(YIGSR), and Ile-Lys-Val-Ala-Val (IKVAV) have been used to enhance cell
adhesion on various surfaces [96,97]. Commonly used peptide sequences used in
tissue engineering applications are summarized in Table 2.
5.1. Covalent immobilzation of ECM-derived peptides to biomaterials
Peptide immobilization on a material is generally accomplished by formation of
covalent bonds between a material surface and introduced components, or rarely
by non-covalent interactions [102]. Non-covalent adsorption of small peptides
onto biomaterial surfaces however, will usually lead to poor immobilization and
in turn, poor cellular attachment. In order to create biomimetic materials that can
withstand long-term survival, stable immobilization of these small peptides to the
biomaterial surface is crucial. The most extensively investigated approach to
immobilize small, bioactive oligopeptide sequences is through covalent coupling
directly to the biomaterial surface. Covalent immobilization via chemical
methods is often times hampered by the lack of chemical reactivity at the
material surface. In order to provide stable covalent linkages between the peptide
and biomaterial, surface reactive groups need to be available on the biomaterial
surface, which is not always the case with certain materials (e.g. polypyrole,
poly(a-hydroxy acids)).
In order to accomplish the covalent immobilization of small peptides onto
chemically inert biomaterials, surface reactive groups must first be introduced or
exposed to serve as coupling sites for the peptide molecules. A number of
methods have been utilized to introduce reactive groups, including graft
polymerization, plasma treatment, hydrolysis, aminolysis, oxidation/reduction
and combinations of the above methods [Table 3]. For example, hydroxyl groups
can be introduced to surfaces via alkaline hydrolysis, while aminolysis can be
produced by reacting surfaces with diamines (e.g. hydrazine hydrate,
ethylenediamine and hexanediamine) resulting in amino-functionalized surfaces
[103]. Once reactive groups are available, various chemical immobilization
schemes can be utilized to create stable covalent linkages usually the N-terminus
amine group of the peptide molecule and the activated surface functional groups
of the biomaterial. Peptides have been immobilized by reacting the N-terminus
amine groups with surface carboxyl, hydroxyl, epoxide and aldehyde groups.
Biomaterials with carboxyl (-COOH) surface functionality can be on
activated using peptide-coupling agents, such as carbodiimides. Water-soluble
carbodiimides, like 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and
the organic-soluble derivative, N,N'-dicyclohexyl-carbodiimide (DCC), serve as
heterobifunctional cross-linkers that mediate the formation of amide bonds