NATURE BIOMEDICAL ENGINEERING 1, 0087 (2017) | DOI: 10.1038/s41551-017-0087 | www.nature.com/natbiomedeng 1
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PUBLISHED: 13 JUNE 2017 | VOLUME: 1 | ARTICLE NUMBER: 0087
O
steoarthritis typically results in joint
movement becoming increasingly
painful where the lubricated
articular surface of the cartilage in the
joint is progressively degraded. In severe
conditions, the replacement of the native
joint with an artifcial one, if medically
possible, can retain patient mobility
1
.
Such artifcial joints are biologically inert
materials designed with optimal chemical
composition, surface charge and roughness
for improved osseointegration; however,
the proteins that adsorb to these surfaces
and foster osseointegration are also the
proteins that encourage bacterial attachment
and subsequent bioflm formation
2
. In
general, artifcial joints comprise either
a mechanically robust metal (commonly
titanium alloy, cobalt/chrome/molybdenum
alloy or tantalum) stem or a composite
stem interfacing with a ceramic or polymer
(usually ultrahigh-molecular-weight
polyethylene; UHMWPE), shaped to mimic
the articulating surface (Fig. 1). In total-joint
arthroplasties, of which the most common
are artifcial hips and knees, success rates for
joint placement and patient satisfaction are
generally high. Depending on the design,
implants can last between 10 and 20 years,
and sometimes longer. When they fail, it is
typically because of either aseptic loosening
or infection of the joint
3
. Aseptic loosening is
mainly associated with material degradation,
infammation, and osteolysis — that is, bone
resorption induced by wear particles.
Infection is an uncommon complication
(average rates are in the 1–2% range)
that leads to implant failure, and is
devastating for patients
4
. During the
primary implantation of the artifcial
joint, such as a hip implant, the synovium
(connective tissue lining the inner surface
of synovial joints and tendon sheath) is
retained as much as possible so that the
implant resides in a similar environment
to the native hip. If bacterial colonization
occurs, poor antibiotic penetrance and
facilitated bacterial bioflm formation in
the presence of the implant leaves little
choice but for a surgical intervention to
remove infected materials. In the case of
an established infection, joint components
are removed, bone surfaces are debrided,
and any remaining synovium is removed.
All joint surfaces are aggressively washed
with various antiseptics. At this juncture,
implantation of a new artifcial joint can
occur — and fxation of the implant is
usually done with bone cement, which
can be used as a reservoir for antibiotics.
Tis type of re-implantation is referred to
as a one-stage revision, and is ofen used
in Europe. Alternatively, an implanted
cement spacer that contains antibiotics
and that can bear some weight serves as
an antibiotic-elution system. Te spacer
is usually retained for at least six weeks,
during which antibiotic elution, which
decreases over time, is designed to prevent
the re-establishment of infection. But the
antibiotic levels in the spacer compromise
its mechanical robustness. Afer six weeks,
if the clinical signs are favourable, the
patient undergoes a revision surgery
with the implantation of a new, usually
cemented artifcial joint, thus completing
the two-stage procedure commonly used
in the United States. With these aggressive
measures, successful eradication of infection
only occurs in 20–90% of the cases
5
. To
improve antibiotic-elution characteristics,
diferent antibiotic controlled-release
systems have been developed
6
, but they
do not elute antibiotics for the necessary
several weeks or have sufcient mechanical
robustness. Reporting in Nature Biomedical
Engineering, Ebru Oral and colleagues now
show that a mechanically robust artifcial
joint designed to include both a long-term
antimicrobial surface and an antibiotic-
elution system
7
allows for long-term
retention of the joint implant, which should
lead to a decrease of surgical procedures and
costs, and ultimately save lives.
Oral and co-authors loaded the
UHMWPE articulating joint with either
vancomycin, or rifampin and vancomycin, a
combination that increases efcacy against
both Gram-negative and Gram-positive
strains of bacteria. One challenge was to
balance the antibiotic-elution levels required
for efcacy (more than three weeks) with
acceptable mechanical properties for the
UHMWPE implant. Te authors found
that drug clusters with eccentric shape and
JOINT IMPLANTS
An elution solution
An optimized drug-eluting polymer for the surface of articulating artifcial joints may make them infection-free.
Noreen J. Hickok
Pelvis
Acetabulum
Femur
Acetabular cup
Femoral head
Textured stem
Native hip
Total-hip
components
Articulating
surfaces
Insert
Cut
Figure 1 | A ball-and-socket hip-joint replacement. The cartilage (blue) coats the femoral head and the
acetabulum; when lubricated by the proteins in the synovial fuid, the joints enjoy essentially friction-free
movement. In a hip replacement, the acetabulum is removed and the femoral head is sawn of. In the
uncemented version shown here, the femoral canal is reamed and the stem of the hip implant is press-ft
inserted into the reamed bone. The replacement acetabular cup is anchored into the pelvis, allowing
re-creation of the ball-and-socket joint. Usually enough synovium remains to allow for the production of
synovial fuid that lubricates the articulating surfaces. Figure adapted from ref.
7
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