journal of the mechanical behavior of biomedical materials
Mechanical, elution, and antibacterial properties of simplex bone cement
loaded with vancomycin
Heidi-Lynn Ploeg a,b,e
a University of Wisconsin, Madison, Mechanical Engineering, Madison, WI, U.S.A b University of Wisconsin, Madison, Biomedical Engineering, Madison, WI, U.S.A c University of Wisconsin, Madison, School of Pharmacy, Madison, WI, U.S.A d University of Wisconsin School of Medicine and Public Health, Madison, WI, U.S.A e Queen’s University – Kingston, Mechanical and Materials Engineering, Kingston, ON, Canada
ABSTRACT
Prosthetic joint infection (PJI) is one of the most devastating failures in total joint replacement (TJR). Infections are becoming difficult to treat due to the emergence
of multi-drug resistant bacteria. These bacteria produce biofilm on the implant surface, rendering many antibiotics ineffective by compromising drug diffusion and
penetration into the infected area. With the introduction of new antibiotics there is a need to create benchmark data from the traditional antibiotic loaded bone
cements. Vancomycin, one of the commonly used antibiotics, shows activity against Methicillin-resistant Staphylococcus aureus (MRSA) and S.epidermidis. In our
study, vancomycin added to bone cement was evaluated for elution properties, antimicrobial properties, and mechanical properties of the bone cement. Vancomycin
at five different loading masses (0.125, 0.25, 0.5, 1.0 and 2.0 g) was added to 40 g of Simplex™ P cement. Addition of vancomycin affected the mechanical properties
and antimicrobial activity with significant differences from controls. Flexural and compression mechanical properties were compromised with added vancomycin.
The flexural strength of samples with added vancomycin of 0.5 g and greater were not greater than ISO 5833 minimum requirements. 2.0 g of vancomycin added to
bone cement was able to eliminate completely the four bacterial strains tested. 2.0 g of vancomycin also showed the highest mass elution from the cement over a 60-
day period. Given the reduced flexural strength in samples with 0.5 g and greater of added vancomycin and the inability of vancomycin in amounts less than 2.0 g to
eliminate bacteria, this study did not find an ideal amount of vancomycin added to Simplex™ P that meets both strength and antibacterial requirements.
1. Introduction
Aseptic loosening and infection after cemented total hip arthroplasty
(THA) and total knee arthroplasty (TKA) are the most common and most
devastating reasons for revision surgery. In 2018 the Swedish Knee
Arthroplasty Register reported an increase in the proportion of TKA
revisions with exchange of inlay, 27% in osteoarthritis (OA) and 24% in
rheumatoid (RA), to treat early infections (Robertsson et al., 2018).
Furthermore, infection rates after surgical revision are 40% higher than
after primary replacement (Trampuz and Zimmerli, 2005). Besides the
considerable cost associated with prolonged hospital (on average $15,
000 – $30,000 for an estimated 7 days in the U.S.), the onset of infection
can cause disfigurement and psychological trauma (Darouiche, 2004).
As a local treatment of the infection site, bone cement loaded with
antibiotics has been used over the last four decades and has become a
common clinical practice. Antibiotic-loaded bone cements (ALBCs) can
deliver high concentrations of antibiotics at the implant site, while
minimizing systemic toxicity (Lee et al., 2016; Letchmanan et al., 2017).
However, there are several notable risk factors that lead to treatment
failure. Infection with Staphylococcus species is associated with a high
risk of treatment failure (Azzam et al., 2010; Byren et al., 2009;
Konigsberg et al., 2014; Koyonos et al., 2011; Marculescu et al., 2006),
likely driven by S. aureus. Methicillin-resistant S. aureus (MRSA) is also
a frequent cause of infection in hospital and community settings that
shows a high rate of treatment failure. MRSA is resistant to many conventional antibiotic treatments; and therefore, management of these
infections is particularly difficult (Kourtis, 2019). S. epidermidis has
emerged as another pathogen implicated in PJI and causes 20% of all
orthopedic device-related infections (Sabate Bresco et al., 2017).
Furthermore, the antibiotic release profile is generally characterized by
an initial burst followed by a low release rate. This release profile is not
ideal since biofilm formation may persist with an increased antibiotic
resistance of the microorganism (Ensing et al., 2008). Because of the
growing resistance of microorganisms to traditional antibiotics, a new
generation of antibiotics and ALBCs are being developed. There is
therefore a need to create benchmark data from traditional ALBCs
* Corresponding author. 4123 Rennebohm Hall 777 Highland Ave, Madison, WI, 53705, U.S.A
E-mail address: [email protected] (W.E. Rose).
Contents lists available at ScienceDirect
Journal of the Mechanical Behavior of Biomedical Materials
journal homepage: http://www.elsevier.com/locate/jmbbm
https://doi.org/10.1016/j.jmbbm.2019.103588
Received 14 August 2019; Received in revised form 6 December 2019; Accepted 7 December 2019
Journal of the Mechanical Behavior of Biomedical Materials 103 (2020) 103588
2
against which the new formulations may be compared.
For long-term fixation of total joint replacements, the mechanical
properties of ALBC are critical. Vacuum mixing (Lewis and Austin, 1994;
Macaulay et al., 2002) is a long established and standard method to
reduce cement porosity. Vacuum mixing has been shown to increase
mechanical properties with a reduction in porosity on the ALBC surface
(Askew et al., 1990; Bishop et al., 1996; Lidgren et al., 1984; Linen and
Gillquist, 1989; Wixson et al., 1987). Numerous studies have investigated the reduction in mechanical properties of ALBCs (Martínez-Moreno et al., 2017). However, how modifications to bone cement affect its
mechanical properties and clinical performance are not well understood.
For instance, Sheafi and Tanner reported a complex relationship between fatigue test specimen shape, fabrication method, and load ratio in
their study with two commercial cements, Smartset GHV (contains
antibiotic) and CMW1 (no antibiotic) (Sheafi and Tanner, 2019). Lee
and co-workers showed sample curing reduced cement mechanical
properties (Lee et al., 2016). Bishop and co-workers tested the static
mechanical properties, cumulative antibiotic release, biofilm inhibition
properties of cured Palacos® R bone cement with various concentrations
of vancomycin (Bishop et al., 2018). Despite many studies of mechanical
properties of bone cement modifications, the fracture toughness,
compression and bending properties of cured Simplex™ P bone cement
with added vancomycin in low doses have not been published. These
data are needed as a benchmark for the next generation of ALBCs with
new antibiotics.
Therefore, the purpose of this study was to quantify the static mechanical properties such as four-point bending strength, compression
strength, and fracture toughness; and, antimicrobial activity and elution
tests were conducted on cured Simplex™ P bone cement loaded with
low doses of vancomycin.
2. Materials and method
2.1. Materials
SimplexTM P was purchased for all tests. The chemical composition of
Simplex™ P is listed in Table 1. Simplex is commonly used in total hip
and knee replacements. Clinical performance of this cement has been
shown to have high rates of prosthesis survival over a 12-year period in
contrast to other cements (Espehaug et al., 2002).
Vancomycin powder was purchased from Sigma-Aldrich (St.Louis,
MO, USA). Vancomycin, one of the commonly used antibiotics (Martinez-Moreno et al., 2017), was chosen for this study because the majority
of the pathogens involved in orthopedic infection are gram positive and
therefore treatable with vancomycin.
2.2. Mixing method
Vacuum mixing was used to mix the bone cement. The cement
powder and antibiotic were mixed by hand-shaking for 1 min in a syringe and then the liquid monomer was added into the antibiotic cement
powder. The small amount of air entrapped in the cement syringe during
mixing was drawn off using a vacuum pump at 50 mbar (Slane et al.,
2014). The cement was then transferred to an aluminum mold by injection with gun pressurization. After delivery of cement to the mold, the
mold cover was placed by hand and pressed against the mold.
2.3. Preparation of antibiotic-loaded bone cement
Six different experimental groups were prepared. The bone cement
with no antibiotic served as a control (Simplex™ P) and five
vancomycin-loaded bone cements were prepared with antibiotic masses:
0.125 g, 0.25 g, 0.5 g, 1.0 g and 2.0 g. Thus, 0.3 vol%, 0.6 vol%, 1.2 vol
%, 2.4 vol%, 4.7 vol% of vancomycin powder were used for the loading
in this study. Four aluminum molds were fabricated for testing samples
with dimensions as described in ISO 5833 for bending and compression
tests (“ISO 5833:2002 Implants for surgery – Acrylic resin cements,”
2002) and ASTM-D5045 for fracture toughness tests. Rectangular prismatic samples
ð6 mm 12 mm; Diameter ½ ∅Height ½hÞ for compression tests;
and rectangular prismatic samples ð44 mm 5 mm 10 mm;
Width ½wDepth ½b Heigh t½hÞ with a crack length of 5 mm and
width of 0.35 mm for fracture toughness tests were fabricated. Cracks
were created using a diamond wafering blade (Buehler® IsoMet™, Lake
Bluff, IL, USA), and measured using ImageJ (National Institutes of
Health and the Laboratory for Optical and Computational Instrumentation, Madison, WI, USA). Cylindrical samples ð6 mm �4:5 mm;
Diameter ½ Height ½hÞ for drug elution and efficacy tests were
also prepared.
2.4. Mechanical testing
Quasi-static mechanical properties were measured under compression and bending. Fracture toughness was also determined. Prior to
mechanical testing, the specimens were wet cured in phosphate buffer
solution (PBS) for 21 days at 22 C (Bishop et al., 2018). Bending tests
and compression tests were conducted in accordance with ISO 5833;
whereas, fracture toughness tests were performed in accordance with
ASTM-D5045. Samples sizes were seven to eight per experimental group
for each test.
The mechanical properties were obtained at loading rates: 5 mm/
min for bending tests; 5 mm/min for compression test; and 10 mm/min
for fracture toughness. Tests were conducted with a Criterion C43.104,
MTS testing machine (Eden Prairie, MN, USA) with a 1 kN load cell
(LPS.103, MTS system Corp). Cylindrical bone cement samples were
compressed in the axial direction until failure occurred (2% yield point)
as recommended by ISO 5833. The ultimate compressive strength (σys ¼
Fmax=A; Fmax ¼ maximum applied load in N before specimen failure, A
¼ original cross-sectional area in mm2
) and elastic modulus in MPa
(Young’s modulus, E, slope at 0.2–0.4% strain) were determined from
the stress-strain curves.
Four-point bend testing (Fig. 1) was performed to measure the
flexural modulus and flexural strength of the bone cement. Rectangular
samples were bent until failure and the flexural modulus was determined from the stress-strain curves. The flexural strength was calculated
using the force at break of the samples. The flexural modulus and
strength were calculated with the following equations:
P ¼ maximum force [N]
S ¼ lower span length [cm]
ac ¼ crack length [cm]
2.5. Drug release study
Five samples in each group were used to measure antibiotic elution.
Each cylindrical sample was immersed in 5 mL of sterile PBS and stored
in an incubator shaker at 37 C with constant shaking at 100 rpm. At
time points, 1, 2, 4, 8, 10, 15, 25 and 45 and 60 days, cylindrical cement
samples were removed from the test tubes. The eluate in each test tube
was frozen at 20 �C until analysis of antibiotic concentration. The
cylindrical cement samples were re-immersed in test tubes containing 5
mL of fresh PBS. Vancomycin concentration in the collected eluate was
quantified by high performance liquid chromatography (HPLC) with a
18 C column (10 μm analytical column and flow rate 0.5 mL/min). The
isocractic mobile phase consisted of 10 mM KH2PO4 – Acetonitrile
(composite ratio, 17/3) and absorbance was measured at 210 nm. A
standard curve was constructed using known vancomycin concentrations. The release profile was characterized by fitting a two-phase
exponential decay function to the elution data as recommended by
Higuchi (Anderson and McConnell, 1999; Higuchi, 1963).
t2 ¼ K2 ¼ Slow decay rate in day-1
2.6. Antimicrobial efficacy testing
Four reference bacterial strains were evaluated for antimicrobial
susceptibility testing: ATCC 33591 (Methicillin-resistant Staphylococcus
aureus [MRSA]), n315 (MRSA), ATCC 29213 (S. aureus), ATCC 35984
(S. epidermidis). The minimum inhibitory concentration (MIC) of vancomycin and inoculum concentration are listed in Table 2 (Dunne et al.,
1993; Kuroda et al., 2001)
Three cylindrical samples were transferred into a test tube containing 3.4 mL of tryptic soy broth (TSB; Becton Dickenson, Pranklin Lakes,
NJ). The broth media were inoculated with bacteria daily for 7 days and
at 14 days and then two-fold serial dilutions were carried out. The
diluted broth media were prepared on Mueller Hinton II agar plates
(Sigma-Aldrich, St. Louis, MO, USA) for bacteria manipulation. Agar
plates were incubated for 18–24 h and bacteria colonies were then
determined. The colony forming unit (CFU) quantified the ability of
eluted antibiotic from the bone cement to eliminate the bacteria in the
cell culture. The minimum detection of bacteria inhibitory was 10 CFU/
mL. All isolates were tested in triplicate for susceptibility.
2.7. Scanning electron microscopy (SEM)
The external, fracture surfaces of four-point bend and fracture
toughness samples, following the test, were examined using a scanning
electron microscopy (SEM; Zeiss-LEO, Oberkochen, Germany). The size
of pores (macro-pore and micro-pore) and the number of pores were
quantified in ImageJ. A thin layer of gold was deposited on the sample
surfaces for 35 s with 45 mA. Images were obtained at 200x magnification using an acceleration voltage of 3 kV.
2.8. Statistical analysis
All the results collected from mechanical testing were statistically
assessed using Minitab 18 (Minitab Inc., State College, PA). KolmogrovSmirnov method was used to determine normality. Kruskal-Wallis tests
and post hoc Mann-Whitney U tests were conducted for non-parametric
comparison between the control group and the groups with vancomycin
added. Wilcoxon Signed Rank test was used to compare mechanical test
Fig. 1. Schematic of the four-point bending test.
Fig. 2. Schematic picture of single edge notch bending test.
Journal of the Mechanical Behavior of Biomedical Materials 103 (2020) 103588
4
results against the minimum ISO requirement. Results are presented as
the mean standard error. A p-value of <0.05 was considered statistically significant.
3. Results
3.1. Mechanical properties
The average flexural modulus for each group exceeded the ISO
minimum requirement (1800 MPa) and there was no statistically significant difference between each group compared with control (mean
2459 155 MPa) (Fig. 3). The flexural strength for all treatment groups
was significantly lower than the control group (mean 63.18 4.77
MPa); and, the flexural strength of samples with 0.5 g and greater were
statistically not greater than the ISO minimum standard (50 MPa)
(Fig. 4).
The compressive modulus of formulated bone cement was not
significantly affected by added vancomycin as compared to the control
group (mean 1694 221 MPa) except for the 2 g of added antibiotic
group (Fig. 5). There is no minimum requirement specified in ISO 5833
standard for compressive modulus. The compressive yield strength was
also not significantly affected by added vancomycin as compared to the
control group (80.59 4.48 MPa) except for the 2 g of added antibiotic
group. All groups were above the minimum compressive yield strength
(70 MPa) in accordance with ISO 5833 (Fig. 6).
The fracture toughness, Mode I critical stress intensity factor, of
Simplex™ P bone cement was statistically significantly higher (p <
0.05) with the addition of vancomycin as compared to the control group
(Mean 1.68 0.16 MPa√m) (Fig. 7).
3.2. Elution properties
All groups exhibited a burst of cumulative elution of vancomycin
(94%–98% of 60-day elution) within a week and a total of 1.5%–2.6% of
vancomycin eluted over the 60-day period (Fig. 8). For the bone cement
samples containing lower amounts of antibiotic such as 0.125 g, 0.25 g
and 0.5 g, the elution profile tended to level off after the initial burst.
The 2 g of added antibiotic group showed the most vancomycin (0.139
0.006 mg) eluted per cement disk. The groups with 1 g and 2 g of added
antibiotic showed much (10x and 30x more than 0.125 g) larger
amounts of vancomycin eluted from cement as compared to the 0.125 g,
0.25 g and 0.5 g of added antibiotic groups. The collected data were
normalized and fit to a two-phase exponential decay function to measure
the fast and slow decay rate. All elution profiles fit the model with coefficient of determination, R2 > 0.99. The parameters, A1 and A2,
represent the magnitudes of the fast and slow phases, respectively. The
decay rates are represented by the parameters K1 and K2, expressed by
1/t1 and 1/t2, respectively. Thus, the fast decay rate for 2 g of vancomycin (and highest elution curve) was K1 ¼ 200 day 1 and the slow
Fig. 3. Flexural modulus of vancomycin formulated Simplex™ P bone cement
after curing process. Solid red line at 1800 MPa indicates ISO 5833 standard for
minimum flexural modulus. Values are shown as the mean and standard error
of the mean for the specimens in each group. Treatment groups were not
different than the control and all groups were above the ISO 5833 minimum
and not different from the control.
Fig. 4. Flexural strength of vancomycin formulated Simplex™ P bone cement
after curing process. Solid red line at 50 MPa indicates ISO 5833 standard for
minimum flexural strength. Values are shown as the mean and standard error of
the mean for the specimens in each group. The asterisk mark (for all treatment
groups) represents a significant (p < 0.05) difference from control group.
Samples with 0.5 g of added vancomycin and greater were statistically not
above the ISO 5833 minimum.
Fig. 5. Compressive modulus of vancomycin formulated Simplex™ P bone
cement after curing process. Values are shown as the mean and standard error
of the mean for the specimens in each group. The asterisk mark (for 2.0 g of
added vancomycin) represents a significant (p < 0.05) difference from control group.
S. Kim et al.
Journal of the Mechanical Behavior of Biomedical Materials 103 (2020) 103588
5
decay rate for 0.125 g of vancomycin was K2 ¼ 1.01 day 1.
3.3. Antimicrobial effectiveness
0.125 g–1.0 g of added vancomycin groups were not able to
completely eliminate the bacterial inoculum below the limit of detection
(10 CFU/mL). In the 2 g of added vancomycin group, the three S. aureus
isolates tended to regrow within a week but no additional bacteria were
observed after one week (Fig. 9).
4. Discussion
The results of this study showed that the mechanical properties of
Simplex™ P bone cement with addition of vancomycin were changed
after 21-days curing in PBS. The flexural modulus was not affected with
increasing amounts of antibiotic but flexural strength was noticeably
decreased with added vancomycin as compared with the control group.
Samples with 0.5 g and greater of added vancomycin were statistically
not above the ISO 5833 minimum. The degradation of flexural strength
with added vancomycin was even more pronounced in the current study
with Simplex™ P bone cement than our previous study with vancomycin
added to Palacos® bone cement (Bishop et al., 2018). In four-point
bending, these material specimens are subjected to a pure bending
moment without shear forces. The specimen is subjected to a linear
gradient of normal stress with compression on the inner curve, tension
on the outer curve and zero stress between at the neutral axis. The
reduction in flexural strength with added vancomycin may be due to a
Fig. 6. Compressive yield strength of vancomycin formulated Simplex™ P bone
cement after curing process. Solid red line at 70 MPa indicates ISO 5833
standard for minimum compressive yield strength. Values are shown as the
mean and standard error of the mean for the specimens in each group. The
asterisk mark (for 2.0 g of added vancomycin) represents a significant (p <
0.05) difference from control group. All groups were above the ISO
5833 minimum.
Fig. 7. Fracture toughness of vancomycin formulated Simplex™ P bone cement
after curing process. Values are shown as the mean and standard error of the
mean for the specimens in each group. The asterisk mark represents a significant (p < 0.05) difference (for all samples with added vancomycin) from control group.
Fig. 8. Vancomycin elution release profiles (mean SEM) over a 60-day period
and two-phase exponential decay model.
Fig. 9. Efficacy test of eluted vancomycin (2.0 g of added vancomycin) for four
strains. All bacterial colonies were completely eliminated at day 7 and no more
colonies were observed afterward. Error bars show mean SEM.
S. Kim et al.
Journal of the Mechanical Behavior of Biomedical Materials 103 (2020) 103588
6
decrease in the material’s tensile strength with increased porosity.
The compressive modulus showed no differences between the
treatment groups and control, except for the group with 2 g of added
antibiotic. This group demonstrated a modulus reduction of 18%, and a
strength reduction of 10%. The reduction in compressive modulus
(17–37%) and yield strength (22%) was even more pronounced for
vancomycin added to Palacos® R (Bishop et al., 2018). Some studies
have reported that adding less than 5% of antibiotic did not significantly
degrade the mechanical properties of cement (Martínez-Moreno et al.,
2017). Lilikakis and Sutcliffe investigated the compression strength of
Palamed G and Copal cements (Heraeus Medical) adding up to 10% vol
vancomycin. They found that all the samples of cement exceeded the ISO
standard for minimum compressive strength (Lilikakis and Sutcliffe,
2009). However, it has been recommended that with the addition of 5%
or less vancomycin, care should be taken with the mixing method, for
example inhomogeneous mixing may reduce the compressive strength
(Lilikakis and Sutcliffe, 2009; Persson et al., 2006). It has also been reported that the strength of cement is reduced depending on the aging
period of the cement samples. Lee and co-workers found a 5–38%
reduction in ultimate compressive strength of Simplex™ P after 2-weeks
curing (Lee et al., 2016).
The fracture toughness of the control group of Simplex™ P (1.69
0:16 MPa√mÞ was similar to previously published results (Bishop
et al., 2018). The groups with added vancomycin showed a statistically
significant increase of 14–19% in fracture toughness in comparison with
the control group. This is in contrast to the flexural strength results and
the author’s previous results with cured Palacos® R which was not
affected by added vancomycin (Bishop et al., 2018). Fracture toughness
of Simplex™ P with added vancomycin has not be published; however,
the results of the current study were similar to those found with the
addition of graphite reinforcement (Robinson et al., 1981) and addition
of titanium fiber reinforcement to the bone cement (Topoleski et al.,
1992). It is also known that pores can increase the apparent toughness
by crack tip blunting (Lee, 2005; Topoleski et al., 1993).
The fracture surfaces were examined with SEM images (Fig. 10).
Pores on the fracture surface were identified as macro pore (diameter
1 mm) and were often observed in the groups with greater than 1 g of
added vancomycin. Persson found from their study that pores larger
than 1 mm in diameter might lead to greater scatter in the static and
fatigue mechanical testing data (Persson et al., 2006). Unlike the results
from Palacos® R cement (Bishop et al., 2018), the micron-sized pores
(diameter 1 mm) were rarely found in Simplex™ P cement.
The total mass of vancomycin elution from Simplex™ P was ten
times lower than the results found from Palacos® R bone cement with 1
g vancomycin (Bishop et al., 2018; Slane et al., 2014). The elution
amount for 1 g of added vancomycin to Simplex™ P was consistent with
the result measured by Meeker (Meeker et al., 2019). Many studies have
investigated antibiotic release dependent on type of bone cement and its
manner of preparation (Martinez-Moreno et al., 2017). Some authors
reported that gentamicin eluted more effectively from Palacos® R than
from Simplex™ P (Hentenaar et al., n.d.; Minelli et al., 2004). The poor
elution of antibiotics from Simplex™ P found in these studies as well as
the current study might be due to several factors, such as the physiochemical characteristics of vancomycin, size of pores and roughness of
bone cement surface (Minelli et al., 2004). Van de Belt reported that a
combination of surface roughness and porosity determine the release
kinetics of gentamicin from bone cement. They found that surface
roughness is related to the initial rates of release of antibiotics from bone
cement and the porosity is related to the sustained release over a longer
period of time (Van de Belt et al., 2000). Other studies have reported
that increasing the ALBC porosity increased the antibiotic elution, so
dextran and glycine were used as space fillers to obtain more porous
ALBC (Kuechle et al., 1991; McLaren et al., 2004). Nugent also showed
that increasing the porosity of ALBC increased the elution of antimicrobials by the addition of soluble particulate poragens (Nugent et al.,
2010).
Our in vitro elution profile demonstrated that bone cement loaded
with 2 g of vancomycin provided antibacterial efficacy against MSSA, S.
aureus, S.epidermidis within the first week. These results are consistent
with previous work on antibacterial activity of vancomycin in bone
Fig. 10. SEM images at 200 magnifications of Simplex™ P bone cement after aging in PBS showing increasing size of pores with increasing amounts of
added vancomycin.
S. Kim et al.
Journal of the Mechanical Behavior of Biomedical Materials 103 (2020) 103588
7
cement against MSSA, MRSA, S.epidermidis (Hsu et al., 2017) and the
authors’ previously published results with Palacos® R (Bishop et al.,
2018).
Some limitations of the present study should be noted. First, the
cement was not tested at body temperature. The test samples were wet
cured and tested at lab temperature as specified in the mechanical test
standards. Mechanical properties determined at body temperature will
differ from the results of the current study (Lee, 2005). All mechanical
properties were determined by assuming linear elastic material behavior
and linear elastic fracture mechanics. However, bone cement is
non-linear viscoelastic material. To reduce this error, the ALBC samples
were tested at relatively low loading rates. The results of this study are
limited to the bone cement, antibiotic and mixing method of this study.
The current study’s results compliment those of other studies. Material
tests as performed in the current study are important for comparing
effects on the cement mechanical properties, and provide material data
for finite element analyses. Cement properties, as determined from
material tests such as those conducted in this study characterize the
cement and not the in vivo performance of an arthroplasty anchored to
the contiguous bone using the cement. Material testing, preclinical
component testing and simulations provide a better understanding of
implant performance, but ultimately in vivo performance can only be
assessed from clinical tests.
5. Conclusion
The mechanical properties of Simplex™ P bone cement were
significantly affected by added vancomycin. In particular, flexural
strength did not meet ISO minimum requirements for 0.5 g and greater
added vancomycin, and compressive modulus and compressive yield
strength were compromised with 2.0 g of added vancomycin. In
contrast, added vancomycin increased fracture toughness of Simplex™ P
bone cement. The total mass of antibiotic elution for the 1 g and 2 g
added vancomycin groups was much higher compared to other groups.
However, only 2 g of added vancomycin were able to eliminate all the
pathogens. Given the reduced flexural strength in samples with 0.5 g and
greater of added vancomycin and the inability of vancomycin in
amounts less than 2.0 g to eliminate bacteria, this study did not find an
ideal amount of vancomycin added to Simplex™ P that meets both
strength and antibacterial requirements.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
CRediT authorship contribution statement
Sunjung Kim: Investigation, Data curation, Formal analysis, Visualization, Writing - original draft. Aaron R. Bishop: Investigation, Data
curation, Visualization. Matthew W. Squire: Resources. Warren E.
Rose: Conceptualization, Methodology, Writing - review & editing.
Heidi-Lynn Ploeg: Conceptualization, Methodology, Writing - review &
editing.
Acknowledgements
The authors would like to thank Dr. Paul Hudson for his assistance in
HPLC data collection. Theravance Biopharma US, Inc., provided funding
support for this work (grant #TLV-2016-002).
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