Biomedical Engineering Reference
In-Depth Information
formation to PEEK implants. This increase in
eukaryotic cell adhesion may reduce implant encap-
sulation and therefore reduce infection risk by
improving the integration of the implant surface with
the immune system.
It is important to investigate the impact of any
surface or surface treatment, to determine cyto- and
biocompatibility, bacterial adhesion, and the risk of
infection using both in vitro and in vivo models. The
complexity of surface chemistry should not be
underestimated. Small changes in surface chemical
composition can affect bacterial adhesion from
a fundamental nonspecific level in basic media to
a highly complex level involving many factors such
as the physiological environment, surrounding tissue,
and the immune system.
inflammatory/prohealing response in vitro
[114]
and in vivo
[115]
.
Much like bacterial adhesion, the immune
response to a biomaterial is dictated by adsorbed
proteins which in turn are controlled by surface
chemistry. An important component of the innate
immune response driven by protein adsorption is
complement activation. Complement molecules bind
to “non-self” surfaces and cause a reaction that
enhances the immune response
[116]
. When the
complement reaction cascade is activated by
a foreign body, a proinflammatory response will
ultimately follow. To that end, the presence of
specific functional groups has been associated with
specific tissue reactions to biomaterials. In particular,
the presence of hydroxyl functionalities has been
linked to biomaterial-mediated complement activa-
tion and subsequent increased inflammatory response
[117
e
119]
. Hydroxyl groups are one of the main
ways by which the body recognizes “non-self”
objects and attracts immune cells to a foreign body.
Conversely, carboxylic acid functionalities do not
alert the immune system to such an extent and could
limit the foreign body response
[117]
. Therefore,
a surface treatment, such as oxygen plasma modifi-
cation (see Chapter 10), to increase the abundance of
more favorable functional groups such as carboxylic
acids, on PEEK, may benefit tissue integration by
decreasing the degree of foreign body inflammation
and decrease the risk of fibrous encapsulation
[117]
.
In addition to surface chemistry, biomaterial topog-
raphy also affects the tissue response. For example,
rougher forms of titanium implants are shown to
decrease fibrous capsule formation in vivo
[120]
.
Additionally, the specific topography of a biomaterial
influences the adhesion of immune cells, such as
macrophages and dendritic cells, necessary for
fighting infection
[121
e
123]
. In reality, a mixed
response of fibrous encapsulation alongside tissue
integration is possible and has been observed asso-
ciated with PEEK implants (Fig. 8.9).
8.3.3 The Role of the Host Immune
Response in Biomaterial-
Associated Infections
In addition to direct biomaterial
e
bacterium
interactions, the immune response to biomaterial
implantation also influences susceptibility to infec-
tion. Upon implantation, all biomaterials will, to
some degree, illicit a foreign body response. The
foreign body response is a complicated process
involving many biological systems and can be further
researched in the relevant literature
[111]
. However,
for the purpose of this chapter, it is important to note
that biomaterial implant design is critical for
a successful application; for example, sharp edges are
known to promote a greater inflammatory response
[112]
. Additionally, novel implants should be fully
characterized with respect to immune response,
biocompatibility, and infection risk before entering
the marketplace. The outcome of the foreign body
response largely depends upon the chemistry and
topography of the biomaterial
[111]
. Some materials
cause a proinflammatory response that enhances
encapsulation by foreign body giant cells and fibrous
tissue growth. This creates a niche for bacterial
infection, isolated from the full extent of the immune
system due to the lack of blood vessels and immune
cells in the vicinity of the implant
[18,113]
. Other
materials cause a prohealing response, where the
implant is integrated into the surrounding tissue and
afforded the full protection of the immune system.
In general, it has been shown that hydrophilic
and negatively charged surfaces lead to an anti-
8.4 Strategies to Reduce Bacterial
Adhesion to PEEK
The strategies used to prevent or limit implant-
associated infection can be divided into two broad
categories: first, antiadhesive surfaces that prevent or
limit the initial adhesion of bacteria to a biomaterial
surface
and,
second,
the
incorporation
of
