Biomedical Engineering Reference
In-Depth Information
One biomimetic surface modification approach to controlling cell-biomaterial surface
reactions is to preadsorb proteins on the implant surface that mimic those most involved
with cell adhesion. The three-amino-acid sequence of Arg-Gly-Asp (RGD) found in fibro-
nectin is now well known for mediating adhesion of cells to surfaces; therefore, RGD-
containing peptides are now being deposited on surfaces to promote cell attachment.
Adsorption of other biological molecules such as growth factors to the surfaces of implants
can control the tissue-biomaterial interaction and lead to enhanced cell activity and more
differentiation than will the cell adhesion molecules alone.
There are many chemical reactions that can be used to attach a biomimetic peptide
sequence to a biomaterial. For example, a protein can be immobilized on a surface through
a technique known as organosilane chemistry (Figure 5.11a). The details of the chemical
coupling and derivitization processes are beyond the scope of this text. Basically, there
are coupling agents such as silanes used to create a covalent bond between the biomaterial
surface and the protein to be attached. Well-ordered protein attachment results. A wide
variety of solid surface modification techniques are available to create the reactive coupling
groups, such as photochemical grafting, chemical derivation, and plasma gas discharge.
Physical adsorption methods utilizing other types of bonding, such as van der Waals and
electrostatic binding, can also be used to immobilize proteins (Figure 5.11b). Physical and
electrostatic adsorption is the easiest technique, but it is the least specific and tends to read-
ily release the adsorbed molecule.
Lipid groups and dye molecules can also be used to immobilize proteins on surfaces.
A critical component of surface modification is the resulting ligand density. If protein
adsorption is too low, the addition of more functional groups to a relatively inert polymer
can be accomplished by plasma glow discharge treatment. The greater reactivity of the
surfaces with higher surface energy after plasma treatment generally leads to increased
tissue adhesion.
Surface modification also can be used to produce protein-resistant surfaces that are
needed in blood-contacting applications such as vascular grafts. For example, polyethylene
oxide has been attached to surfaces to reduce protein adsorption. Cell adhesion was signifi-
cantly reduced on these treated surfaces. Anticoagulants can also be attached to biomaterial
surfaces to decrease unwanted cell attachment. Various hydrophilic biomaterials have been
shown to reduce platelet adhesion and thrombus formation. Hydrophilic materials have
also been shown to hinder bone healing, so what is appropriate for one biomaterial appli-
cation does not necessarily apply to another.
FIGURE 5.11
Two types of chemical reactions
used to modify a biomaterial surface: (a) covalent
coupling techniques where S
¼
the silane/oxygen
bond with the surface and R
the reactive group
that attaches to the protein, and (b) physical adsorp-
tion methods utilizing electrostatic interactions.
Negatively charged proteins are shown attaching
to a positively charged biomaterial surface.
¼
