Biomedical Engineering Reference
In-Depth Information
several studies which showed that VEGF aids in healing bone defects [65-68] . Coating Ti6Al4V
implants with collagen and poly(2-hydroxyethyl methacrylate-2-methacryloyloxyethyl phosphate)
(P(HEMA-MOEP)) loaded with VEGF has also been tested and shown to improve vascularization
within the implant [69] . Moreover, immobilized VEGF on titanium alloy substrates coated with thin
adherent polydopamine films induces the differentiation of human mesenchymal stem cells into endo-
thelial cells [70] .
8.3 NANOTOPOGRAPHY AND PROTEIN ABSORPTION
Surface modification of titanium implants to create nanotopography on the implant surfaces has been
shown to increase the adsorption of proteins, leading to an increase in cell adhesion, proliferation,
and subsequently osseointegration. Adsorption of proteins produced by blood cells on the titanium
implant is of critical importance, especially immediately after the implantation procedure. The pro-
teins presented in blood plasma include albumins, fibrinogen, and immunoglobulins. Once the pro-
teins have been adsorbed onto the implant surface, they act as the interface between the surface and
the cells. As shown by a previous study, adsorption is not only affected by the texture of the tita-
nium implant, but also by the surface chemistry and hydrophobicity [71] . An implant made of tita-
nium slows the process of blood clotting while reducing the adhesion of platelets when compared
to other materials such as steel [72] . To increase the surface roughness of the Ti implant surfaces
for protein adsorption, coating of the implant surface with carbon nanotubes has been used [73] . For
example, F-actin more readily adsorbs onto a surface with a groove height of 1-2 nm than it does
on a surface with a height of 4 nm or greater. The nanostructure can also affect the orientation of the
adsorbed proteins such as fibronectin [74] and alter the conformation of the RGD containing proteins
like fibronectin and vitronectin [41] . In general, nanotopography can alter protein interactions with an
implant surface, leading to an increase in cell activities including osteoblast adhesion.
8.4 NANOTOPOGRAPHY ALTERS OSTEOBLAST RESPONSES
The cellular response of osteoblast cells to titanium surfaces depends on a variety of factors including
structures and dimensions of the nanotopography as well as types of cells and materials. The poten-
tial impacts include changes in cell morphology, adhesion, proliferation, and production of other
bioactive molecules ( Figure 8.1 ). Osteoblasts are cells that are primarily responsible for calcium dep-
osition and formation of bone including teeth. They work in tandem with osteoclasts, which resorb
bone, to constantly regulate bone formation. Cellular responses including cell morphology, adhesion,
and proliferation toward the titanium-modified surfaces in vitro and in vivo are summarized in Tables
8.3 and 8.4 , respectively.
8.4.1 Cell Morphology
Like most cells, osteoblast cells react by changing their morphology to suit the environment that
they grow in. Osteoblasts maintain a rounded shape without extensions when they are on a flat tita-
nium surface, whereas the titanium nanotube array causes the cells to become elongated, showing an
 
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