Biomedical Engineering Reference
In-Depth Information
the impregnation of silver into polyurethane and
silicone catheters
[142,172,173]
. Such bulk loading
removes the risks of coating delamination through
scratching, low surface adhesion, and the uncon-
trolled release of silver from the surface. Bulk
incorporation of silver has already been used, for
example, in silver
e
polyamide composites, or in
bone cement composites
[180]
, where nanosilver
particles are added during the monomer-mixing
phase
[177]
; both have shown promising silver ion
release profiles and inhibition of common peri-
prosthetic infection pathogens
[177,180]
. Because of
the inherent high-temperature stability of silver
particulates along with its broad spectrum of anti-
microbial activity, work conducted in our laborato-
ries has investigated whether these particulates can
be incorporated into PEEK to enhance the antimi-
crobial activity of the materials used in the various
PEEK applications.
8.4.4 Silver
In addition to chemical agents such as antibiotics,
heavy metals such as silver, gold, and copper are
also antimicrobial. For medical devices, silver
has emerged as a popular choice due to its wide range
of activity against both Gram-positive and Gram-
negative bacteria and also fungi. Furthermore, silver
shows a relatively low cellular toxicity when
compared with other heavy metals
[165
e
167]
and is
neutralized by resident intracellular metallothioneins
[168]
. However, like most antimicrobial drugs, the
dose and release of silver should still be minimized to
reduce the potential for toxicity
[169,170]
. Silver
particles are already used in medicine, notably in the
treatment of burn wounds
[171]
. Additionally, the use
of silver has been investigated for use as antimicro-
bial coatings in a number of implants such as cath-
eters, heart valves, and external fixation pins
[172
e
174]
. Various silver-treated devices including
central venous catheters and burn wound dressings
have already reached the market with regulatory
board approval.
The antimicrobial properties of silver primarily
arise due to the denaturing interactions of silver ions
with sulfur-, oxygen-, and nitrogen-containing func-
tional groups of biological molecules
[165,175,176]
.
The thiol groups (
e
SH) of structural proteins and
respiratory enzymes key to bacterial survival are
therefore altered by the presence of silver ions
[175]
.
This can lead to cell wall structural damage, reduc-
tion in cell metabolism, and loss of resistance to
harmful oxidative reactions
[165,175]
. Silver ions
have also been observed to cause bacterial DNA to
condense as a defense mechanism against denatur-
ation. This condensation results in the arrest of
replication as the DNA is no longer in the required
relaxed conformation
[176]
. Because of the multiple
interactions of silver ions with bacteria, the risk of
developing resistance through single genetic muta-
tions is greatly reduced in comparison with
commonly used antibiotics
[165,176,177]
.
To impart the antimicrobial properties of silver to
a biomaterial, a number of techniques have been used
including the co-sputter of silver and hydroxyapatite
(HA) onto substrates, physical vapor deposition
(PVD), and spin casting
[178
e
180]
.However,in
some cases, coatings of silver reportedly show poor
adhesion and lack of uniformity
[180,181]
. Recently,
silver has been added directly to molten polymers for
incorporation into the bulk matrix; examples include
8.4.5 SilverePEEK Composites
For polymers such as PEEK, impregnation of
antimicrobial agents into the bulk biomaterials is
preferable to coating due to the risk of delamination
or loss of the antimicrobial material. However,
because the melt temperature of PEEK is 343
C
[182]
, most antimicrobial agents would at the very
least be inactivated during fabrication of the
composite material. Thus, silver additives have
become ideal candidates for the development of
a well-dispersed infection-resistant PEEK composite.
Initial investigations performed by D. Jaekel on
silver-impregnated PEEK included three silver-based
additives resistant to high-temperature degradation:
a nanosilver powder, a porous silver particulate, and
a silver ceramic composite powder (
Table 8.4
). These
three compounds represent an array of particle
morphologies and size. To demonstrate the efficacy
of the additives, the raw silver products were incor-
porated
in
agar
gels
at
low concentrations
(100
e
200
g/ml; ~19 ppm) and shown to impede
S. aureus and E. coli growth.
State-of-the-art extrusion and injection-molding
techniques were used to integrate the additives into
PEEK. The three proposed silver
e
PEEK material
combinations were molded at two weight ratios (2%
and 5%) with no apparent material deformation,
voids, or significant dimensional variations. All
materials were evaluated for antimicrobial efficacy
against S. aureus surface colonization for time points
m
