Biomedical Engineering Reference
In-Depth Information
migration, and thereby enhancing bone formation and osseointegration. A biologic organic matrix or
biomolecular layer covalently bound to titanium surface can effectively modulate osteoblast response.
The potential advantage of delivering organic molecules directly to the bone-implant interface is that
it could be used to control orientation of biomolecules to cells, therefore inducing favorable intracel-
lular and extracellular responses to accelerate bone formation.
6.2.3
Biochemical Modification of Titanium Surface
Biochemical modification of titanium surface has been achieved through the following ways:
l
Osteoinductive biomolecular cues (cell-adhesive proteins and peptides) passively adsorbed or cov-
alently bound to titanium surface.
l
Micro- and nanoscale coating of hydroxyapatite (HA)/calcium phosphate/alumina coatings with
bioactive molecular cues, osteoinductive growth factors, and antibacterial drugs.
l
Organic nanoscale self-assembled monolayers (SAMs) with chemically linked biomolecular cues,
osteoinductive growth factors, and drugs.
l
Bioactive, biodegradable hydrogels with incorporated biomolecules and osteoinductive growth
factors.
l
Antibacterial agents or antibacterial drug delivery directly from titanium surface to decrease pri-
mary bacterial adhesion and prevention of biofilm formation in order to reduce the risk of peri-
implantitis-induced implant failure.
6.2.3.1 Osteoinductive Biomolecular Cues
Osteoinductive biological macromolecules have been delivered from titanium surface to study their
role in modulating osteoblast response and enhancing osseointegration. These biomolecules have
been passively adsorbed or covalently bound to the titanium surface.
In-vitro
studies with passively
adsorbed extracellular matrix proteins like fibronectin and vitronectin on titanium surface showed
increased osteoblast adhesion, proliferation, and differentiation when compared with bare titanium sur-
faces and those coated with vitronectin
[43]
. Fibronectin and collagen type I and III adsorbed onto
Ti-6Al-4V surface have significantly influenced the behavior of rat osteoblasts in terms of alkaline
phosphatase activity and collagen synthesis
[44,45]
. Since these passively bound biomolecules can be
washed off or removed easily, covalent binding on to the titanium surface was advocated. Collagen
has been covalently bound through acrylic acid grafting onto a hydrocarbon plasma film deposited on
titanium surface. An
in-vivo
study on rabbit femur model showed enhanced bone healing with the col-
lagen-modified titanium surface
[46]
.
Another approach utilized anodic oxidation (anodization) to fabricate oxide layer (TiO
2
) on tita-
nium surface. Collagen type I was immobilized by partial incorporation onto this oxide layer
[47]
.
In-vitro
studies with stimulated body fluid (SBF) showed spherical calcium phosphate formed on
immobilized fibrillar collagen (FC) type 1 on titanium specimen with air-formed passive layer (AFP)
(
Figure 6.2
)
[47]
. The limitations of delivering whole proteins or protein fragments from titanium
surface include the risk of 3D structure deformation leading to protein denaturation, protein conju-
gation, or protein-induced immunological reactions
[17]
. In order to address these limitations, recent
approaches have focused on using short synthetic or natural peptides that present the bioadhesive
motif. The most frequently used bioadhesive peptide motif is the arginine-glycine-aspartic acid
(RGD) sequence which mediates bone cell attachment to several extracellular matrix proteins like
fibronectin, vitronectin, BSP, and OPN
[48]
.
