BIOMIMETIC MATRICES FOR INTEGRIN-MEDIATED CELL ADHESION - Biologically-Responsive Hybrid Biomaterials - page 251

Table 3. Summary of common surface functionalization and activation techniques.

Functionalization
techniques

Reactive
Moiety

Activating agent References

Carbodiimides (EDC, DCC);
long spacer arm (NHS)

Hydrolysis Carboxyl [106,129]

GL, DSG, phenylene
diisothiocyanate

Aminolysis Amino [109-111]

Highly reactive sulfonyl
chlorides (tres chloride); DSC;
p-NPC

Alkaline hydrolysis Hydroxyl [114,126-128]

2,2,2-trifluoroethanesulfonyl chloride (tresyl chloride) [114]. Surfaces can be
pre-activated with tresyl chloride [115-118] to yield sulfonated surfaces that are
susceptible to nucleophilic attack by primary amines, thiols and imidazole groups
[119-121]. Further, tresyl chloride can activate hydroxyl-containing biomaterials,
such as silica and agarose, to form tresylated hydroxyl groups and couple
enzymes and peptides by direct reaction with their primary amine groups or
sulfhydryl side-groups [11,119]. FN cell-adhesive proteins and Polymyxin B
peptide antibiotic have been successfully immobilized on Ti surfaces [122-124],
and ethyl acrylate and 2-hydroxyethyl methacrylate copolymers [125],
respectively, via tresyl chloride reactions. Alternatively, surface hydroxyl groups
can also be activated with N,N'-disuccinimidyl carbonate (DSC) or p-
nitrophenyl chlorocarbonate (p-NPC) and coupled with peptides under aqueous
conditions [110,126-128].
Chemoselective ligation is a more recent approach to chemically modify
biomaterial surfaces. This process immobilizes peptide molecules to biomaterial
surfaces via stable covalent bonds by selectively coupling unique and mutually
reactive functional groups under mild conditions without the need of activating
agents or interfering with other functional groups [130]. These reactions are
highly chemoselective and behave like molecular “velcro” [131]. Oxime ligation
is a chemoselective reaction between aldehyde groups and hydroxyl amino
groups and serves as a site-specific method to link unprotected aminooxy-
functionalized peptides to material substrates. Researchers have used aminooxy-
aldehyde coupling reactions to attach proteins and aminooxy-terminated RGD
cyclopeptides to various substrate surfaces [132,133]. Hydrazone ligation has
been used to immobilize synthetic hydrazine-like peptides onto aldehyde- or
ŋ -oxoaldehyde-functionalized surfaces. Synthetic peptidoliposomes have been
prepared by chemoselectively creating ŋ -oxohydrazone bonds between