Review

Viscoelastic properties of injectable bone cements for orthopaedic

applications: State-of-the-art review
Gladius Lewis
Department of Mechanical Engineering, The University of Memphis, Memphis, Tennessee 38152
Received 13 August 2010; revised 8 December 2010; accepted 10 February 2011
Published online 18 April 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.31835
Abstract: Injectable bone cements (IBCs) are used for a vari-
ety of orthopaedic applications, examples being poly (methyl
methacrylate) (PMMA) bone cements used for anchoring total
joint replacements (TJRs) (high load-bearing application),
PMMA bone cements used in the vertebral body augmenta-
tion procedures of vertebroplasty (VP) and balloon kypho-
plasty (BKP) (medium load-bearing application), and calcium
phosphate-based and calcium sulfate-based cements used as
bone void llers/bone graft substitutes (low load-bearing appli-
cation). For each of these applications, the viscoelastic proper-
ties of the cement are very important. For example, (1) creep of
the cement has an inuence on the longevity of a cemented
TJR (for example, creep allows the cement to remodel, thereby
maximizing the contact area of the cement-bone interface and,
hence, minimizing stress concentration at that interface); and (2)
in VP and BKP, the likelihood of cement extravasation is directly
related to the prole of the viscosity-versus-time elapsed from
commencement of mixing of the cement. There are a few
reviews of the literature on a number of viscoelastic properties
of some IBCs but a comprehensive review of the literature on
all viscoelastic properties of all IBCs is lacking. The objective of
this contribution is to present such a review. In addition, a num-
ber of ideas for future study in the eld of viscoelastic proper-
ties of IBCs are described. VC
2011 Wiley Periodicals, Inc. J Biomed
Mater Res Part B: Appl Biomater 98B: 171191, 2011.
Key Words: bone cement-PMMA, acrylic, calcium phos-
phates, mechanical properties
INTRODUCTION
Injectable bone cements (IBCs) are used in a wide assort-
ment of applications, notably bone augmentation procedures
(in, for example, orthopaedic and maxillo-facial surgeries)
and bone reconstruction (in, for example, lling of a bone
cyst). On the basis of chemistry, IBCs may be classied as
acrylic bone cements (ABCs), calcium phosphate-based
cements (CPCs), calcium sulfate-based cements (CSCs), and
lamentary composite materials. Alternatively, on the basis
of the nature of the orthopaedic application, IBCs may be
grouped into those for high load-bearing applications
(ABCs), medium load-bearing applications (ABCs, some
CPCs, and some CSCs), and low load-bearing applications
(some CPCs and CSCs).
For the past 50 or so years, ABCs specically, poly
(methyl methacrylate) (PMMA) bone cements have been
widely used as the anchoring/grouting agent in total hip
joint replacements (THJRs) and total knee joint replace-
ments (TKJRs)
1,2
as well as in a large variety of other joint
replacements (TJRs), such as those of the ankle,
3
elbow,
4
the proximal interphalangeal joint,
5
and shoulder.
6
In a
cemented TJR, the main functions of the cement are to im-
mobilize the implant, transfer body weight and service loads
from the prosthesis to the bone, and increase the load-car-
rying capacity of the prosthesis-bone cement-bone system.
7
ABCs, some CPCs, and a FCM are used in vertebroplasty
(VP) and balloon kyphoplasty (BKP), which are surgical
methods for treating osteoporosis-induced pathological
fractures of the vertebral body (vertebral compressive
fractures).
810
The essence of these methods involves injec-
tion of a dough of an IBC through a cannula and under uo-
roscopic guidance either directly into the fractured verte-
bral body (VP) or into a cavity created in the fractured
vertebral body by the ination of an inatable balloon tamp
(BKP).
810
The goals of these methods are to augment the
fractured vertebral body (VP and BKP),
810
stabilize it (VP
and BKP),
810
and/or restore it to as much of its normal
height and functional state as possible (BKP).
810
CPCs and CSCs are widely used as injectable bone void
llers/bone graft substitutes, in which they are injected into
surgically created osseous defects (for example, treatment
of complicated bone cysts in children
11
) or bone defects cre-
ated secondary to traumatic injury to the bone (for example,
augmentation of the xation of displaced intra-articular cal-
caneal fractures.
12
) In the US, there are $900,000 hospital-
izations per year to treat fractures
13
and $800,000 bone
graft procedures are performed each year.
14
For the purposes of the present review, viscoelastic
properties of an IBC refer to creep, stress relaxation, damp-
ing, the prole of the viscosity-versus time following
Correspondence to: G. Lewis; e-mail: glewis@memphis.edu
VC 2011 WILEY PERIODICALS, INC. 171
commencement of mixing of the cement constituents (mix-
ing time), and strain rate dependence of mechanical prop-
erties. In the case of ABCs, these viscoelastic properties are
important for the following reasons. First, in the case of
cemented TJRs, the viscosity of the cement dough at the
time of its insertion into the prepared bone bed exerts a sig-
nicant inuence on the nature and extent of interdigitation
of the cement into the contiguous bone, which, in turn,
affects the integrity of the cement-bone interface.
15
This
interface has been identied as one of the three weak zones
in a cemented TJR (the others being the cement mantle
itself and the cement-implant interface) and its integrity is
postulated to have a signicant impact on the in vivo lon-
gevity of a TJR.
16
Arguably, the most prominent difference
among the myriad commercially available PMMA bone
cement brands is in the viscosity of the polymerizing
cement-versus-mixing time prole.
17
Second, it has been
suggested that, in a cemented TJR, a small amount of
cement creep may, in fact, be benecial, especially in the im-
mediate post-implantation period.
15
For example, a polished,
tapered, collar-less femoral stem of a THJR relies on a
certain amount of cement subsidence for the implant to re-
model in the cement bed, which, in turn, facilitates cement-
implant interlocking, thereby increasing the stability of the
implant and increasing the in vivo longevity of the TJR.
15
Furthermore, cement creep may cause stresses in the
cement mantle to change from being tensile to being com-
pressive, a situation that is desirable because the compres-
sive strength of an ABC is much greater than its tensile
strength.
7
Also, it has been suggested that, in a cemented
TJR, cement creep may be benecial in helping to relieve
residual stresses built up in the cement during the polymer-
ization of the cement.
18
It is worth noting that, notwith-
standing the three aforementioned points on cement creep,
it is generally agreed that, in a cemented TJR, a high amount
of cement creep is undesirable as it leads or contributes to
loosening and/or subsidence of the implant.
19
Third, as far
as use of IBCs for applications such as VP and BKP is con-
cerned, the viscosity of the polymerizing cement-versus-mix-
ing time prole is directly correlated with the prole of the
variation of the pressure (force) required to inject the
cement paste through the cannula with time of injection. At
any time of injection, one component of that pressure is
that required to overcome the yield strength of the cement
paste and to initiate ow of the cement while the other
component is the pressure required to maintain the ow
of the cement dough/slurry. This latter component is
directly related to the viscosity of the cement slurry. The
cement viscosity is important from another perspective;
namely, upon injection into either the fractured vertebral
body (VP) or the void created in the fractured vertebral
body by the bone tamp (BKP), the viscosity of the cement
dough must be low enough to allow penetration through
the cancellous bone but not to permit extravasation, which
is a serious complication.
20
The aforementioned points indi-
cate that the cements viscosity-mixing time prole ulti-
mately affects both the feasibility and the outcome of VP
and BKP.
20
Over the years, a number of reviews of the literature on
IBCs have appeared but they are limited in a number of
respects as far as the viscoelastic properties of these materi-
als are concerned. First, in reviews that covered a wide
range of properties of ABCs, such as those by Lewis,
7
Saha
and Pal,
21
Hasenwinkel,
22
Serbetci et al.,
23
Deb,
24
and
Boesel,
25
treatment of viscoelastic properties was either
very brief and incomplete
7,2123,25
or absent.
24
Second, there
has been only one review that focused on viscoelastic prop-
erties of ABCs but it only covered the literature on apparent
viscosity-versus-mixing time proles and was published
nearly 30 years ago.
17
Third, a number of reviews have
appeared on the properties of CPCs and CSCs that have
been used or have the potential for use in VP and BKP,
2631
but viscoelastic properties were not discussed in any of
them. Fourth, the present author is unaware of any review
of viscoelastic properties of FCMs, as used in VP and BKP.
Fifth, viscoelastic properties were not included in reviews
of properties of bone void llers/bone graft substitutes.
3234
The purposes of the present contribution were to pres-
ent a comprehensive review of the literature on all the
viscoelastic properties of all chemistries of IBCs and to high-
light areas for future research in this eld. In support of the
rst-mentioned purpose, a detailed search was conducted of
relevant databases (such as MEDLINE
VR
/PubMed and
PubMed Central), science subjects-specic search engines
(such as SCIRUS
VR
) and the table of contents of relevant key
journals (such as Journal of Biomedical Materials Research
Part B: Applied Biomaterials, Biomaterials, and Journal of
Materials Science: Materials in Medicine) for relevant peer-
reviewed articles published, over the period 1975-date, in
English as well as in other languages. Furthermore, the
references list of each article, obtained from this search,
was manually examined to identify additional relevant
articles. The review is organized into four parts, with these
being containing, in order, reviews of the literature on ABCs,
reviews of the literature on CPCs, discussion of future
research topics, and a summary of the most salient points
made in the work.
ACRYLIC BONE CEMENT
Creep deformation
Specimen constraint and loading conditions in experi-
mental tests. In a creep test, a specimen is positioned in
the testing machine (typically, the specimen is enclosed in
an environmental chamber) and then subjected to a speci-
ed type of loading, with the response of the specimen (typ-
ically, its deformation) being continuously monitored until
either the specimen fractures or the test is terminated after
a certain length of time. Two types of specimen constraints
have been used; namely, unconstrained and constrained. In
the former case, the specimen is unsupported along its
sides
3552
while, in the latter case, the specimen is placed
between a steel outer jacket and a stainless steel inner
core, simulating the restraint between the implant and
the cancellous bone in a cemented TJR.
5355
Two types of
loading congurations have been used. One is quasi-
static;
3538,40,4246,4952
specically, a 10:1 lever-arm
172 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
deadweight set up,
36
a cantilever-type testing machine,
40
a
four-point bend test rig,
43
or a three-point bend test rig.
49,51
The other is dynamic/cyclical, under load control,
39,41,47,48,5255
with some of the tests run on commercially available universal
materials testing machines,
39,41,47,48
others on a commer-
cially available pneumatic actuator,
52
and others on a com-
mercially available hip joint simulator.
5355
Inuencing factors
Brand of commercially available cement. There are
many similarities and differences between the large number
of commercially available PMMA cement brands on the basis
of a number of parameters, such as composition (Table I),
size of the prepolymerized PMMA beads in the powder (D
b
),
powder particle size distribution, mean powder particle
size, molecular weight of the powder, molecular weight of
the cured cement, and the prole of change in viscosity of
the curing cement dough as a function of time following
mixing of the powder and liquid monomer.
For unconstrained specimens aged in water, at 37

C, and
then tested in water, at 37

C, using a pneumatic actuator,

(1) the creep strain of laboratory-fabricated Palacos R Cum
Gentamicin specimens was signicantly higher than that of
laboratory-fabricated CMW3G specimens; and (2) the creep
strain of Palacos R Cum Gentamicin specimens, fabricated
from retrievals following revision of THJRs for aseptic loos-
ening of the implant, was signicantly lower than when
Boneloc specimens, also fabricated from THHR retrievals,
were used.
52
It has been suggested that, under certain
circumstances, cement creep, in a cemented TJR, may be
benecial as it allows adaptation between the implant and
the cement. This postulate is supported by good outcomes
in two hospital series in which Boneloc was used to anchor
the femoral component of the Exeter THJR.
56
(It is noted
that, with most THJR designs, however, outcomes when
Boneloc was used were very poor, loading to withdrawal of
the cement from the market in 1994.
57
)
For constrained specimens, tested in body temperature
under dynamic loading conditions, the dynamic creep strain
(e
c
) values, at 250,000 cycles, were 5500 microstrain and
4500 microstrain for Palacos R and CMW1 specimens,
respectively.
54
The volume-weighted mean values of D
b
for
Palacos R and CMW1 are 55 lm and 44 lm, respectively.
54
The trends in these e
c
results
54
appear to be in consonance
with the suggestion that, with increase in D
b
, there is
increase in the potential for formation of crevice (which act
as stress risers), culminating in increased creep deformation.
54
The trends in the aforementioned e
c
results obtained
using constrained Palacos R and CMW1 specimens under
dynamic loading conditions have also been explained on the
basis of difference in two other cement parameters.
54
The
rst was the molecular weight of the cement powder
(MW
p
), with the postulate being that since MW
p
of Palacos
R cement is higher than that for CMW1, the beads of the
former cement swell less and dissolve less, leading to more
crevices in the specimens of the former cement.
54
The sec-
ond parameter was the difference between MW
p
and the
molecular weight of the cement matrix (MW
m
) for a given
cement, with this difference affecting the magnitude of the
contact stresses at the matrix-bead interface. These stresses
are implicated in debonding of beads from the matrix, cul-
minating in creation of microcracks. which, under dynamic
loading, may propagate through the specimen. In the case of
Palacos R, MW
m
< MW
p
, whereas, for CMW1, MW
m
>
MW
p
.
54
Under quasi-static compressive stress, the mean creep
strain, at a given combination of stress and time, of Omniplas-
tic (low-viscosity brand), Surgical Simplex P (medium-vis-
cosity brand), and Zimmer Regular (medium-viscosity
brand) specimens was between 8% and 83% higher than
that for Zimmer Low Viscosity
VR
specimens.
36
At any time
during a quasi-static four-point bending creep test on uncon-
strained specimens, at 37

C, creep deection of specimens of

Palacos R cement (high-viscosity brand) was signicantly
larger than that for specimens of CMW1 (high-viscosity
brand), Surgical Simplex P, CMW1, and Palacos LV40 (low-
viscosity brand).
43
These results point to the possibility of a
trend of decrease in creep resistance with increase in cement
viscosity.
For unconstrained specimens in a dynamic compression
test on specimens immersed in Ringers solution, at 37

C,
the mean creep strain, after 250,000 cycles, was higher for
Mendec specimens compared with that for KyphX speci-
mens, a trend that was consistent with the trend of higher
density (q) of KyphX cement (and, hence, lower porosity of
KyphX specimens).
47
The signicance of q in creep resist-
ance of a cement is claried when the results from speci-
mens fabricated from a family of cements with essentially
the same composition are considered. Thus, for uncon-
strained hand-mixed specimens immersed in Ringers
solution, at 38.5

C, dynamic compressive strain of Cemex

Isoplastic (high q) specimens were $16% to $34% lower
compared to the values obtained for Cemex System
(medium q) and Cemex RX (low q) specimens.
41
It thus
appears that low creep strain may be correlated with high
cement density.
For unconstrained specimens subjected to quasi-static
three-point bending, the creep deformation, under similar
loading proles and for a given specimen aging time (in
water, at 37

C), of SmartSet GHV specimens was, on

average, marginally higher than that of Palacos RG speci-
mens,
51
a trend that is not consistent with the fact that the
content of the gentamicin sulfate, which acts, in essence, as
a plasticizer, in the former cement is twice that in the latter.
It is noteworthy that there were no signicant differences in
either t
o
(which is one of the parameters in the expression
that relates the creep compliance to the time, as given in
the Kohmrausch creep law
58
for the cement) or g
0
(which is
the viscosity of the damper-element in a modied Burgers
creep constitutive model of the cement) between the two
cements.
51
For unconstrained specimens aged in water, at
37

C, and then tested in water, at 37

C, using a pneumatic
actuator, the creep strain of laboratory-fabricated Palacos R
Cum Gentamicin specimens was signicantly higher than
that of laboratory-fabricated CMW3G specimens,
52
even
though the gentamicin sulfate content of both cements is
REVIEW ARTICLE
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 173
the same. These results
51,52
indicate that the inuence of
gentamicin sulfate on creep performance is unclear.
Composition of experimental cement. Under quasi-
static compressive stress, reinforcing PMMA bone cement
with either bers or particulates led to substantial reduc-
tion in a specied creep parameter.
35,36,50
These reductions
(relative to the value for unreinforced cement specimens)
amounted to between $33% and $64% in mean creep
strain after a given time when 2 wt/wt % chopped carbon
bers were added to the cement
35,36
; and between $37%
and $68% decrease in creep compliance at 10
5
s when ei-
ther 10 wt/wt % or 20 wt/wt % hydroxyapatite (HA) pow-
der was added to a PMMA bone cement, respectively.
50
For
the carbon ber-reinforced cement, the trends were attrib-
uted to the formation, at a given applied stress, of interpore
cracks in unreinforced cement specimens and their absence
in reinforced cement specimens.
36
For the HA-reinforced
cement, the trends were consistent with the fact that, after
a creep test, the reinforced cement specimens showed
slower and less complete recovery than the unreinforced
ones, which may be attributed to some separation of the HA
particles from the polymer matrix during creep.
50
For a hydrophilic, partially degradable and bioactive
cement, (1) an increase in the amount of the hydrophilic
monomer led to a signicant decrease in the cements creep
rate
45
; (2) consistent with a priori expectation, incorpora-
tion of glass particles into the cement led to a cement with
increased creep resistance under bending, a trend attribut-
able to the formation of an apatitic layer
46
; and (3) in free
swelling, its creep rate is higher than that of commercially
available cements.
45
Monomer-to-polymer ratio (MPR). In the case of two
cements used in VP (Osteopal V and Vertebroplastic), there
was no signicant difference in the creep deformation of
specimens, as obtained in quasi-static four-point bend tests
conducted in distilled water, at 37

C.
49
This trend is
TABLE I. Compositions of a Sample of Commonly Used Commercially Available Injectable Bone Cements
Cement Type/Brand Name Composition/Constituents
a,b
Manufacturer/Supplier
Acrylic Bone Cements
CMW
TM
1 Powder (40.00 g): 35.54 g PMMA, 3.64 g
BaSO
4
, 0.82 g BPO
DePuy CMW Blackpool, UK
Liquid (18.37 g): 18.22 g MMA, 0.15 g
DMPT, 25 ppm HQ
KyphX
VR
HV-R
TM
Powder (20.00 g): 13.60 g MMA-styrene co-
polymer; 6.00 g BaSO
4
, 0.40 g BPO
Medtronic Spinal & Biologics,
Sunnyvale, CA, USA
Liquid (9.00 g): 8.92 g MMA (monomer),
0.08 g DMPT, 75 ppm HQ
Palacos
VR
R Powder (40.00 g): 33.55 g poly(methyl acry-
late, MMA), 6.13 g ZrO
2
, 0.32 g BPO, 1.00
mg chlorophyll
Heraeus Kulzer GmbH, Hanau,
Germany
Liquid (18.78 g): 18.40 g MMA, 0.38 g
DMPT, 0.40 mg chlorophyll
Surgical Simplex
VR
P Powder (40.00 g): 29.40 g poly(MMA, sty-
rene), 6.00 g PMMA, 4.00 g BaSO
4
, 0.60 g
BPO
Liquid (18.79 g): 18.31 g MMA, 0.48 g
DMPT, 80 ppm HQ
Calcium phosphate-based
cements
Biopex
VR
a-TCP, TTCP, DCPD Mitsubishi Materials Corp., Tokyo,
Japan
chronOS Inject
VR
Powder: 42 wt.% b-TCP, 21 wt.% MCPM, 31
wt.% b-TCP granules, 5 wt.% Mg hydro-
gen phosphate trihydrate, < 1 wt.% so-
dium hydrogen pyrophosphate Mg(SO
4
)
2
Oberdorf, Switzerland
Liquid: 0.5% solution of sodium hyalurone
Norian
VR
Skeletal Repair
System
a-TCP, CaCO
3
, MCPM Synthes, Inc.,West Chester, PA, USA
Calcium sulfate-based cements
AlloMatrix
VR
CaSO
4
.0.5H
2
0; demineralized bone matrix Wright Medical Technology,
Arlington, TN, USA
MIIG
VR
X3 CaSO
4
.0.5H
2
0 Wright Medical Technology
Filamentary composite cement
Cortoss
VR
bis-GMA, bis-EMA, TEGDMA, glass
particles
Orthovita, Malvern, PA, USA
a
MMA, methylmethacrylate; BPO: benzoyl peroxide; DMPT, N, N-dimethyl-p-toluidie; HQ, hydroquinone; TCP, tricalcium phosphate; TTCP, tet-
racalcium phosphate; DCPD, dicalcium phosphate dihydrate; MCPM, monocalcium phosphate monohydrate; GMA, glycidyl dimethacrylate;
EMA, ethoxydimethacryylate; TEGDMA, triethyleneglycol dimethacrylate.
b
Compositional details for the acrylic bone cements and chronOs Inject
VR
cement were taken from products brochures.
174 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
inconsistent with the relative MPRs for the cements; speci-
cally, MPR for Osteopal V is lower than that of Vertebro-
plastic,
59
leading to the expectation of higher creep resist-
ance of specimens of the former cement.
Polymerization pressure. Polymerization pressure (p)
is the pressure that is applied to the cement dough during
the preparation of a test specimen. For both Mendec and
KyphX cement specimens, over a range 170 kPa p
3200 kPa, mean creep strain, as determined in dynamic
compression tests on specimens in Ringers solution, at
37

C, decreased with increase in p, a trend that was attrib-

uted to an increase in cement density (and, hence, decrease
in porosity of the specimens) accompanying the increase
in p.
47
Cement mixing method. Under quasi-static compressive
loading, over the stress range of 3050 MPa, the mean
creep strain of unconstrained specimens of Palacos R and
Zimmer R, kept moist, was signicantly lower on specimens
fabricated from vacuum-mixed cement compared to hand-
mixed cement, which was attributed to a signicant reduc-
tion in porosity brought about with vacuum mixing.
39
Duration of cement mixing. An increase in the time
interval between the beginning of vacuum mixing of the
cement constituents and injection of the curing dough into
the specimen mold (from 90 s (standard injection) to
270 s (delayed injection)) signicantly increased the creep
strain of unconstrained Palacos R specimens subjected to
quasi-static compressive loading while immersed in saline
at 37

C.
40
Similar trends in strength values were attributed
to the formation of laminations within delayed injection
specimens.
60
Length of aging time
Under quasi-static tension loading (stress 3 MPa), the
creep rate of specimens of a PMMA bone cement, at any
creep time, decreased with increase in length of aging (7
24 days) in a given test medium (air, water, Ringers solu-
tion, or Intralipid (a fat solution designed to simulate the
fat in the bone cavity)), a trend that was consistent with
work on physical aging.
42
For unconstrained Surgical Simplex P specimens sub-
jected to quasi-static four-point bending, creep deection
decreased signicantly with increase in the aging time of
the specimens, t
a
(dened as the time interval between
immersion of the specimen in saline at 37

C (1 h t
a

28 days) and testing in saline at 37

C).
43
This trend was
attributed to the reduction of the plasticizing inuence of
the liquid monomer with increase in t
a
as the monomer
content was reduced by continued polymerization.
43
For unconstrained Palacos RG and SmartSet GHV speci-
mens subjected to quasi-static three-point bending, creep
compliance decreased signicantly with increase in aging
time (dened as the time interval between immersion of
the specimen in water, at 37

C, and testing in Ringers solu-

tion, at 37

C) (over the range 45 min to 2.5 years), a trend

that was related to the mobility of the polymer chains.
51
For both SmartSet GHV and Palacos RG specimens, the
inuence of length of the time the specimens were aged (in
demineralized water, at 37

C) prior to the creep test (t

e
), on
the creep of the specimens was the same; specically, linear
increase of log t
o
with log t
e
and linear increase of g
0
with log t
e
.
51
While the experimental evidence shows unanimity that
increase in aging time led to decrease in a given creep
parameter,
42,43,51
various explanations have been put
forward for this trend.
Test medium composition. Under quasi-static loading, the
mean creep strain rate of Sulx 6 and Zimmer LVC speci-
mens was signicantly lower when tested in water than in
air, which points to the possibility that the creep resistance
of the bone cement in a cemented TJR may not be compro-
mised.
61
Under quasi-static compressive loading, the mean
creep strain rate of unconstrained Surgical Simplex P speci-
mens tested in intramedullary fat at a given temperature
(37

C or 40

C) was between 2.34 and 2.52 times that when

the testing medium was saline, a trend that was attributed
to the plasticizing effect of the fat.
43
Under quasi-static tension loading, the creep rate of
specimens of a poly(ethyl methacrylate) (PEMA) bone
cement (aged and tested in the same solution, at 24

C), at
any test temperature, was signicantly inuenced by the
test medium, with the rate being similar in distilled water
and Ringers solution, each rate of which was higher than in
Intralipid, which, in turn, was higher than in air. These
trends were explained by the plasticization by each of the
water-based media (water and Ringers solution) and the
increase of leaching of the monomer from specimens tested
in Intralipid.
42
Test medium temperature. Under quasi-static tension load-
ing (stress 3 MPa), the creep rate of specimens of a
PEMA bone cement, tested in a given medium (air, water,
Ringers solution, saline, or Intralipid) increased with
increase in the medium temperature (T); for example, in air,
in the range 24

C T 50

C, there was a very small

increase in the rate in going from 24

C to 30

C and from
30

C to 40

C, and a very large increase between 40

C and
50

C.
42
In dynamic loading tests on restrained hand-mixed
CMW 1 and Palacos R specimens, creep strain when the
specimens were tested at body temperature was substan-
tially higher than when tested at room temperature, after
the initial creep stage (i.e., at number of test cycles >
1,271,400 cycles).
54
These trends
54
suggest that an increase
in test medium temperature increases the effects of plastici-
zation and are consistent with creep in a given test medium
being considered a thermally activated process.
62
Constraint of test specimen. Under dynamic creep condi-
tions, the creep strain of fully restrained hand-mixed
CMW2000 specimens, in room-temperature air, was signi-
cantly lower than when the specimens were semi-
restrained.
53
This trend is consistent with creep being
described as a consequence of stretching and realignment of
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 175
TABLE II. Empirical Relationships for Creep Strain of Commercially Available PMMA Bone Cement Specimens
Cement brand Test Conditions Empirical Relationship
a,b
Reference
Cemex Dynamic compression log e 0.3386 log N 4.449 Verdonschot and Huiskes
41
Isoplastic Hand-mixed
Unconstrained
Saline, at 38.5

C
Cemex RX Dynamic compression log e 0.3743 log N 4.366 Verdonschot and Huiskes
41
Hand-mixed
Unconstrained
Saline, at 38.5

C
Cemex Dynamic compression log e 0.3101 log N 4.148 Verdonschot and Huiskes
41
System Mixed within a syringe
Unconstrained
Saline, at 38.5

C
CMW1 Dynamic tension log e [0.13 log r 0.42] log N Jeffers et al.
48
Vacuum-mixed [3.12 log r 2.61]
Unconstrained
Distilled water, at 37

C
CMW1 Dynamic compression e (%) 0.099 ln N 1.178 Liu et al.
54
Hand mixed
Fully constrained
Test medium temperature:
Room temperature
CMW1 Dynamic compression e (%) 0.176 ln N 2.151 Liu et al.
54
Hand mixed
Fully constrained
Test medium temperature:
Body temperature
CMW2000 Dynamic compression e (%) 0.088 ln N 1.029; Liu et al.
53
Hand-mixed r
2
0.925
Fully constrained
CMW2000 Dynamic compression e (%) 0.088 ln N 0.7989; Liu et al.
53
Hand-mixed r
2
0.898
Semiconstrained
Palacos R-40 Dynamic compression e (%) 0.069 ln N 0.622 Liu et al.
54
Hand-mixed
Fully constrained
Test medium temperature:
Room temperature
Palacos R-40 Dynamic compression e (%) 0.2002 ln N 2.371 Liu et al.
54
Hand mixed
Fully constrained
Test medium temperature:
Body temperature
SmartSet Dynamic compression e (%) (0.448N)/(1,063,111 N); Liu et al.
55
GHV Hand mixed r
2
0.96
Semiconstrained
Test medium temperature:
Room temperature
SmartSet Dynamic compression e (%) (1.787N)/(180,332 N); Liu et al.
55
GHV Hand mixed r
2
0.99
Semiconstrained
Test medium temperature:
Body temperature
SmartSet Dynamic compression e (%) (0.410N)/(1,184,562 N); Liu et al.
55
GHV Hand mixed r
2
0.97
Fully constrained
Test medium temperature:
Room temperature
Surgical Dynamic compression e
c
1.22 10
5
N
0.31
10
0.03r
Verdonschot and Huiskes
39
Simplex P Hand-mixed
Unconstrained
Saline, at 38.5

C
Surgical Dynamic compression log e 0.3488 log N 4.426 Verdonschot and Huiskes
41
Simplex P Hand-mixed
Unconstrained
Saline, at 38.5

C
Zimmer Quasi-static compression e 1.76 10
9
r
1.858
t
0.283
Chwirut
36
Regular Hand-mixed e 3.02 10
4
e
(9.37 10-4r)
t
0.283
Unconstrained
Saline, at 37

C
a
e is creep strain; r is applied stress (in MPa) (except, Chwirut,
36
in which r is in lbs in
2
); t is test time (in h); N is number of loading cycles.
b
r
2
is the coefcient of multiple determination of the tted equation.
molecule chains in the cement in that, in a fully restrained
specimen, there is a limited amount of these processes.
54
Nature of applied loading. The number of test cycles (N)
(and, hence, time) required until the creep strain equals the
elastic strain of an unconstrained cement specimen
(applied stress on specimen/elastic modulus of cement),
at a given stress level, may be computed using a best-t
relationship (derived from experimental results; for exam-
ples, see Table II). This time (which is inversely pro-
portional to the creep rate) was signicantly shorter under
cyclical tensile load than under cyclical compressive load, at
stresses > 5 MPa.
39
Furthermore, these times, as obtained
from dynamic compression tests, were signicantly higher
than under quasi-static compression, at stresses > 5
MPa.
36,39
Magnitude of applied stress
Under quasi-static tension loading, the creep rate of speci-
mens of a PEMA bone cement, in a given test medium (air,
distilled water, Ringers solution, or Intralipid), increased
markedly with increases in the magnitude of the applied
stress, which reects the fact that, with increase in stress in
a given test medium, there is increase in the plasticization
effect of the medium.
42
Empirical relationships and modeling. A number of em-
pirical relationships have been derived from experimental
results (Table II), any of which may be used to obtain esti-
mates of long-term creep strain.
In terms of modeling, the time-temperature superposi-
tion principle (TTSP), Struiks effective time method
(SETM),
63
and the integrated time function method (ITFM)
have been applied to compliance (or creep) results for a
commercial acrylic cement and an experimental cement
(PEMA cement).
44,50
TTSP involves three steps. The rst is to compute the
horizontal shift factor, a
T
, using, in most cases, the Struik
equation for compliance, D, at a given test temperature and
test time, t, along with a
T
. Thus, the governing equation for
D(t) is
63
Dt D
o
expt:a
T
=s
m
; (1)
where D
o
is the initial compliance and s and m are con-
stants. For the PEMA cement, at T 37

C, the best-t val-

ues of the constants were: D
o
3.33 GPa
1
, s 7305 s,
and m 0.276.
50
The second step is to determine the qual-
ity of the t of the Williams-Landel-Ferry (WLF) equation to
the experimentally obtained results for the variation of a
T
with T. This equation is given as
64
loga
T

C
1
T T
s

C
2
T T
s

(2)
where T is the temperature of the test medium, T
s
is a ref-
erence temperature (usually, taken to be the glass transition
temperature of the cement) and C
1
and C
2
are constants
(Figure 1). The third step is to generate the master time-
temperature extrapolated creep compliance (or creep rate)
plot. For the commercial acrylic cement, it was found that,
with C
1
17.4 and C
2
75 K, the t to the experimental
creep compliance (and, hence, rate) results was excellent
(Figure 2).
SETM is used to account for the inuence of aging of
the specimen. The essence of this method is that it may be
used to determine the effective time of a creep test (k),
which is dened as the time required to achieve the same
creep strain if aging had been ongoing. The expression used
to compute k is as follows:
k t
e
t
c
a
t
e
1
_ _
1=a
1
_ _
(3)
where t
e
is the aging time, t
c
is the actual creep time, and
a (1-l), with l (the aging rate) being the slope of the
plot of log a
T
versus log t
e
. For a PEMA cement with experi-
mentally obtained compliance-time results, at 1 MPa, 37

C,
and 1 day of prior aging, the superior performance of
SETM compared with when TTSP was used is evident
50
(Figure 3).
ITFM involves three steps. The rst is to generate the
momentary creep curve, with physical aging not being con-
sidered important. This is done by obtaining the t between
the experimental creep data, on one hand, and either the
Struick equation [Eq. (4)] or the Williams-Watts equation
65
[Eq. (5)], on the other.
Dt D
0
exp
t
s
_ _
m
(4)
Dt D
o
DD
a
1 expt=s
m
(5)
FIGURE 1. Variation of shift factor, a
T
, with test temperature, T, and
the t between the Williams-Landel-Ferry (WLF) equation and the ex-
perimental results, for a poly (ethyl methacrylate) bone cement. (With
kind permission from Springer ScienceBusiness Media; Journal of
Materials Science: Materials in Medicine, Prediction of the long-term
creep behaviour of hydroxyapatite-lled polyethylmethacrylate bone
cements, volume 18, 2007, page 1854, J. C. Arnold and N. P. Venditti,
Figure 6).
REVIEW ARTICLE
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 177
where D, t, D
o
, s, and m have the same meanings as given
before and DD
a
is a material constant.
The second step is to use results from a long-term creep
test, where aging is important, to obtain values of C and b
as used in the integrated time function. This is accom-
plished thus: (1) plot the equation
FDt
t
st
(6)
with the F(D(t)) applicable to the Struik equation [see
Eq. (7)] or to the Williams-Watts equation [see Eq. (8)].
Dt D
0
exp
_
t
0
du
u
_
_
_
_
m
(7)
Dt D
0
DD
a
1 exp
_
t
0
du
u
_
_
_
_
m
_
_
_
_
(8)
where u is a dummy time variable.
(2) The slope of this plot [i.e., of Eq. (6)] gives the varia-
tion of s(t), whence C and b may be obtained using the
following equation
_
t
0
du
su
where s
2
t s
2
C
2
t
2b
(9)
The third step is to use the values of the constants
obtained (D
o
, s, m, C, and b, if Eq (7) is used or D
o
, s, m, C,
b, and DD
a
if Eq (8) is used) to construct predictive curves
from which the long-term creep data may be read. For a
PEMA cement, the best-t values of the material constants
found were found to be: D
o
2.558, s 2.097 s, m
0.245, C 0.240, and b 0.817 (for t between Eq. (7)
and the experimental data) and D
o
3.900, s 8.00 10
7
s, m 0.601, C 2820, b 0.674, and DD
a
400 GPa
1
,
(for t between Eq. (8) and the experimental data).
50
A
comparison of the creep compliance versus creep time
results, for one set of experimental conditions, to the predic-
tions using the two variants of the ITFM [i.e., via use of
Eq (7) or of Eq (8)] is shown in Figure 4.
FIGURE 3. Experimentally obtained long-term creep compliance-ver-
sus-test time data (recorded data) for a poly (ethyl methacrylate) bone
cement, together with the master curve generated using the time-tem-
perature superposition method and the data computed using Struiks
effective time method. (Experimental data obtained at 1 MPa; Ringers
solution, at 37

C; and 1 day of aging in Ringers solution, at 37

C.)
(With kind permission from Springer ScienceBusiness Media; Jour-
nal of Materials Science: Materials in Medicine, Prediction of the
long-term creep behaviour of hydroxyapatite-lled polyethylmethacry-
late bone cements, volume 18, 2007, page 1855, J. C. Arnold and N.
P. Venditti, Figure 11).
FIGURE 2. Extrapolated creep compliance results at 37

C and 2 MPa
for a commercial acrylic cement, obtained using the time-tempera-
ture superposition method. The temperatures shown are the test tem-
peratures used. Plots were obtained using the following best-t
values for the parameters in the Williams-Landel-Ferry equation: C1
17.4 and C2 75 K. (With kind permission from Springer Science-
Business Media; Journal of Materials Science: Materials in Medicine,
Creep behavior of bone cement: a method for time extrapolation
using time-temperature equivalence, volume 14, 2003, page 324, R. l.
Morgan, D. F. Farrar, J. Rose, H. Forster, and I. Morgan, Figure 5(b)).
FIGURE 4. Experimentally obtained long-term creep compliance-ver-
sus-test time data (recorded data) for a poly (ethyl methacrylate) bone
cement, together with predictions computed using integrated time
functions given by Sruik [Eq. (7)] and Williams and Watts [Eq. (8)].
(Experimental data obtained at 1 MPa; Ringers solution, at 37

C; and
1 day of aging in Ringers solution, at 37

C.) (With kind permission

from Springer ScienceBusiness Media; Journal of Materials Science:
Materials in Medicine, Prediction of the long-term creep behaviour of
hydroxyapatite-lled polyethylmethacrylate bone cements, volume 18,
2007, page 1857, J. C. Arnold and N. P. Venditti, Figure 12).
178 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
A phenomenological description of the creep compliance
(J(t)) of Palacos RG and SmartSet GHV specimens,
obtained in three-point bending (range of specimen aging
time in demineralized water, at 37

C: 45 min to 2.5 years;

test medium: Ringers solution, at 37

C; applied stress (r):

10 MPa or 25 MPa) has been given in terms of the Struik 3-
parameter creep law.
51
This law is given as
Jt J
0
exp
t
t
0
_ _
m
_ _
(10)
where J
o
, t
o
, and m are the parameters.
A physical description of the creep deformation of the
aforementioned Palacos RG and SmartSet GHV specimens
was presented in terms of the modied Burgers model,
51
which is given by
et r
1
E
0

1
E
r
1 e
t=sr

t
g

1
E
c
1 e
t=sc

_ _
(11)
where E
o
is the modulus of elasticity of the cement; 1/E
r
and s
r
are the weight and time constant of the viscoelastic
relaxation, respectively; g is the viscosity of the cement;
and 1/E
c
and s
c
are the weight and time constant of the pri-
mary creep phase, respectively.
Summary. Two observations are in order here. First, in
spite of the existence of results from a multitude of studies,
the inuence of various intrinsic and extrinsic factors on
the creep performance of commercially available PMMA
bone cement brands is unclear. This is because the majority
of these studies were not designed to delineate these
aspects. As a result, many of the studies are limited by the
presence of confounding variable(s), the most common of
which was the use of different commercially available
brands. This situation makes it difcult to, for example,
assess the impact of a combination of extrinsic factors that
are clinically relevant (for example, cement mixing method,
nature of applied stress, and magnitude of stress) on the
creep performance of a given cement brand. Second, there
is limited information on the appropriate model(s) for the
creep behavior of PMMA bone cements. This hampers the
development of rational method(s) of synthesizing a cement
brand from the perspective of creep deformation.
Stress relaxation
Cement composition and cement brand. For a surgical
grade cement, at a constant compressive strain of 1%, at a
given value of time during the test, the extent of stress
relaxation increased when the cement was reinforced by
incorporating 2 wt/wt % chopped carbon ber into the
cement powder.
35
The rate of stress relaxation was signicantly higher in
Palacos R (stress relaxed to practically zero after 6 weeks)
compared with both CMW1 and Simplex P (in both, stress
relaxed to 100 kPa after one year).
66
During unconstrained stress relaxation tests, conducted
under quasi-static four-point bending, the relaxation of the
load in Surgical Simplex P specimens, with time, when
tested in saline solution at 37

C, was not signicantly differ-

ent from that for Palacos
VR
R specimens tested in the same
medium.
44
The loads for both of these sets of specimens
were, however, signicantly different than those obtained
when specimens fabricated from the family of CMW were
used.
43
The trend in the above results for Surgical Simplex P
and CMW1
43
were different from that determined from
three-point bend tests on CMW1-G and Surgical. Simplex P
specimens, at initial strain of 0.3% or 0.6%, or 0.9%.
67
In
the latter case, the reduced stress functions for these two
cements were the same.
67
For a given combination of con-
stant strain and time, the stress in specimens of either
CMW1-G and Surgical Simplex P was higher than in speci-
mens of another commercially available cement, Braxell.
67
Aging time. At any time during unconstrained stress relaxa-
tion tests, conducted under quasi-static four-point bending,
the stress in Surgical Simplex P specimens, when tested in
saline solution at 37

C, increased signicantly with increase

in conditioning time of specimens in the solution, t
m
(1 h
t
m
10 weeks).
43
This same trend was seen when the
tests were carried out, in air at room temperature under
tension (1 h t
m
7 days)
43
and in another series of four-
point bending tests (conducted in water, at 37

C.)
68
The trend in these results
43,68
was attributed to reduction
of the plasticizing effect of the monomer with increase
in t
m
.
43
Empirical relationships and modeling. The experimental
evidence (Table III) indicates that, for a given cement, the
relaxation of compressive stress with time in the specimen
may be modeled using the Maxwell viscoelastic model.
Experimental data obtained on hand-mixed Surgical Sim-
plex P specimens, tested in four-point bending, in water at
37

C, were described by the Maxwell double-exponential

model (Figure 5); thus, the stress (r)-versus-t relationship
is of the form
r ae
t=b
ve
t=d
c; (12)
where a, b, v, d, c are constants, each of which is related to
a material property; for example, b g
1
/E
1
and d g
2
/E
2
.
For specimens aged, in air, at 37

C, for 70 days, the best-t

values of a, b, v, d, c were found to be 3.51, 5.10, 10.52,
159.31, and 10.70, respectively.
68
From the results on three-point bend tests on Braxell,
CMW1-G, and Surgical Simplex P specimens, conducted in
water at 37

C (together with those from damping tests

these are discussed in the next section of this review), the
constitutive equation that links the drop of elastic modulus,
E, with time, t, was found to be
67
Et E
1
DEt E
1
C
1
expt=s
1

_
1
0
Ks expt=sds (13)
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 179
with K(s) C
2
/s C
3
/s
n
and E
1
, C
1
, C
2
, C
3
, s, and n are
constants. That is, this drop is describable using one main
relaxation time (s
1
) superimposed on a continuous spec-
trum of relaxation times. For example, for Surgical Simplex
P specimens, the best-t values of E
1
, C
1
, C
2
, C
3
, s, and n
were found to be 1000 MPa, 1300 MPa, 130 MPa, 15, 9
10
4
s, and 1.1, respectively.
67
Each of these models [Eqs. (12) and (13)] allows a pre-
diction of the long-term extent of stress relaxation of a
cement specimen on the basis of results obtained in the
short-term.
Summary. The literature is very limited in a number of
respects, such as studies on only a few commercially avail-
able cement specimens, investigations of only a few inu-
encing factors, and a few contributions in the area of
modeling.
Damping
Background. The ability of a viscoelastic material, such as
an ABC, to dissipate strain energy as heat can be deter-
mined using a dynamic test. Such a testing mode is relevant
to ABC being used in a TJR, in which, during activities of
daily living, the cement mantle is subjected to cyclical load-
ing. The essential relationship in damping studies recog-
nizes that a given modulus of the cement is a complex
parameter; for example, the complex elastic modulus (E) is
E E
0
iE
00
(14)
where E
0
is the storage modulus and characterizes the mate-
rials elasticity, and E is the loss modulus and characterizes
its internal damping capacity.
Thus,
Loss=damping factor; tan d E
00
=E
0
(15)
(Note that Eqs. (14) and (15) may also be written in terms
of the shear modulus, G.)
Test mode. With one exception, dynamic mechanical ther-
mal analysis (DMTA) (sometimes referred to as dynamic
mechanical analysis, DMA), operated in three-point bending
mode, has been used to determine E
0
, E
00
, and tan d, as a
function of the cured cement specimens temperature, T
0
(at
a xed test frequency, f).
6971
In a DMTA test, typical speci-
men size is 25.040.0 mm 10.0 mm 1.01.5 mm, and
typical test conditions are: displacement, 64 lm; static force,
60 mN; dynamic force, 40 mN; rate of heating of specimen,
24

C min
1
; range of T
0
: 20200

C; and range of f 1
30 Hz.
6971
The exception is a study in which the DMTA
tests were performed on cured cement specimens, in a dis-
placement control mode; that is, using a frequency sweep
(0.01100 Hz) and a temperature sweep (1757

C).
67
Damping properties may also be obtained using a plate-
plate congured rheometer (typical radius of plates and gap
between them 2025 mm and 2 mm, respectively), oper-
ated in a dynamic oscillation (constant strain) mode
FIGURE 5. Schematic drawing of the spring-dashpot model for the
stress relaxation behavior of a PMMA bone cement. (Reprinted from
Proceedings of the Institution of Mechanical Engineers, Part H: Jour-
nal of Engineering in Medicine, volume 216, number 3, O. R. Eden, A.
J. C. Lee, and R. M. Hooper, Stress relaxation modeling of polyme-
thylmethacrylate bone cement, pages 195-199, copyright (2002), with
permission from Professional Engineering Publishing).
TABLE III. Empirical Relationships for Stress Relaxation of Commercially Available PMMA Bone Cement Specimens
Cement Test Conditions Empirical Relationship
a,b
Unit for t Reference
Braxell Hand-mixed r 4.18 e
0.0054t
; s De Santis et al.
67
Stored in distilled water, at 37

C, r
2
0.643
for 21 d
Tested in water
Three-point bend loading
Palacos R Hand-mixed r 20.49 e
0.020t
; h Lee et al.
43
Stored in saline, at 37

C, for 7 d r
2
0.766
Tested in saline, at 37

C
Four-point bend loading
Simplex P Hand-mixed r 19.14 e
0.0104t
; min Eden et al.
68
Stored in air, at 37

, for 6 h r
2
0.889
Tested in water, at 37

C
Four-point bend loading
Surgical grade r 18.91 e
0.286t
h Pal and Saha
35
a
r is stress, in MPa.
b
Empirical relationship was given explicitly in the article by Pal and Saha,
35
but each of the other three empirical relationships was derived
by the present author from experimental results given in the original article.
180 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
(typically, strain amplitude and frequency 1% and 1
5 Hz, respectively), with the curing cement being tested at a
xed temperature.
7275
Typically, results in a damping study are presented as
(1) the variation of the storage modulus, the loss modulus,
and/or tan d with specimen temperature, at a xed test fre-
quency [Figure 6(a)] and/or (2) the variation of the storage
modulus, the loss modulus, and/or tan d with test time (t)
at a xed combination of T
0
and f [Figure 6(b)].
Inuence of cement composition. In the case of a PMMA
bone cement, in which the radiopacier was provided by
BaSO
4
particles (10% p/p) in the cement powder, when dry
cured specimens were used, the storage modulus, at a given
T
0
, was practically the same as when radiopacity was pro-
vided by incorporating an iodine-containing monomer, 4-
iodophenol methacrylate (IPMA) (520% v/v), in the liquid
phase.
70
The same trend was found for the tan d results.
70
In the case of a PMMA bone cement in which the radio-
pacier was provided by BaSO
4
particles (10%) in the
cement powder, when dry cured specimens were used,
the storage modulus, at a given T
0
(f xed), was practically
the same as when radiopacity was provided by any one of
three other radiopaciers (10% bismuth salicylate (BS)
incorporated in the powder; BS coated with polyethylene
oxide incorporated in the powder (BSPEO); and BS dis-
solved in the liquid monomer (BSDM)).
71
The same trend
was found for the tan d results.
71
Up to t
m
$16 min, the
pattern of increase of G
0
with increase in time from com-
mencement of mixing of the cement, t
m
(at a xed combina-
tion of T
0
and f) was practically the same when the radiopa-
cier was 10 wt % BaSO
4
particles in the powder as when
any one of three other radiopaciers incorporated in the
cement powder (10 wt % strontium hydroxyapatite (SrHA),
10 wt % SrHA treated with MMA (SrHA-m), and 20 wt %
SrHA-m).
75
For t
m
> $16 min, there were similarities and
differences seen in the plots for the four cements: for the
10 wt % BaSO
4
-containing cement, there was a sharp rise
in G
0
(corresponding to an increase in polymerization); for
the 20 wt % SrHA-m-containing cement, there was a slow
rise in G
0
for up to t
m
$10 min, followed by a sharp rise
thereafter; and for each of the other two cements, G
0
increased at the same rate as during t
m
$16 min.
75
All of
the aforementioned patterns were also seen in the G
00
results.
75
Inuence of cement brand. In a displacement control
mode experiment, (1) up to f 10 Hz, the mean value of
tan d for the cured Braxell specimens was about the same
as for the cured CMW1 and Surgical Simplex P specimens;
(2) in the range 10 Hz < f < 100 Hz, tan d for the cured
Braxell specimens was marginally higher than for the other
two cured cement specimens; and (3) the increase in tan d,
with increase in f, was slightly greater for the cured Braxell
specimens compared with those of the other cements.
67
These results suggest that the main factor that inuences
the damping factor in a PMMA bone cement is the constitu-
ent of the main polymer chain; in other words, since PMMA
is the main polymer in Braxell, CMW1, and Surgical Simplex
P, their tan d-f prole was about the same.
67
Inuence of size of PMMA beads. For experimental PMMA
bone cements designed for use in VP and BKP, at a given
value of t
m
(for a xed combination of T
0
and f), a decrease
in the ratio of large PMMA beads (mean diameter 118
lm) to small ones (mean diameter 70 lm) (we designate
this ratio R, in wt /wt %) in the powder led to an increase
in both G
0
and G
00
.
72
This trend was attributed to the disso-
lution of the small beads (and, hence, the beginning of
increasing polymerization rate) appearing earlier as R
increases.
72
Inuence of state of hydration of test specimens. In the
case of a PMMA bone cement in which the radiopacier was
provided either by adding BaSO
4
particles (10% p/p) to the
cement powder or by incorporating IPMA (520% v/v) in
the liquid phase, for both dry and wet cured specimens, at a
given T
0
(f xed), the pattern of change of storage modulus
with test temperature was unaffected by the state of hydra-
tion of the test specimen.
70
For the tan d results, (1) for
each cement, there was a broadening of the plots when wet
specimens were used compared to when dry ones were
used, which was attributed to a plasticizing process
70
; and
FIGURE 6. (a) Typical variation of the storage modulus and the loss
angle (tan d) with temperature of a cured PMMA bone cement speci-
men, obtained at 2 Hz. (b) Typical variation of storage modulus, loss
modulus, and tan d of a curing PMMA bone cement dough, with test
time, obtained at room temperature of 22

C and test frequency of

1 Hz.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 181
(2) there was a slight reduction of the temperature at which
the peak occurred, dropping from a mean of $127

C when
dry cured specimens were used to a mean of $115

C when
wet cured ones were used in the case of the BaSO
4
-contain-
ing cement and from a mean of $129

C to a mean of
$116

C when dry and wet cured IPMA-containing cement

specimens were used, respectively.
70
These same trends
were obtained in the case of a PMMA bone cement in which
the radiopacity was provided by BS, BSPEO, or BSDM.
71
Inuence of test frequency, f. In a displacement control
mode experiment, for a given cement (Braxell, CMW1, or
Surgical Simplex P), with tests conducted on cured speci-
mens immersed in water, after conditioning them in distilled
water, at 37

C, for 21 days, each of the dynamic properties

(storage modulus, loss modulus, and loss factor) increased
with increase in f.
67
It has been suggested that this phenom-
enon may provide an explanation for the fact that, although
PMMA bone cement is brittle, under quasi-static loading,
it provides excellent resistance to dynamic loading (that
is, it acts as a shock absorber), as is experienced in
the cement in a TJR during many activities of daily living,
notably gait.
76
Inuence of test temperature (T). In a displacement con-
trol mode experiment on Surgical Simplex P specimens, at a
given value of f (0.1 Hz 1 f 10.0 Hz), there was a trend
of increase of tan d with increase in T,
67
a trend that is con-
sistent with damping of the cement being a thermally acti-
vated process.
62
Modeling. From the results on three-point bend tests on
cured Braxell, CMW1, and Surgical Simplex P specimens,
conducted in water (together with those from stress relaxa-
tion testsstress relaxation results are presented in a pre-
vious subsection of this review), it was found that an appli-
cable model is one that contains an exponential part (which
would provide an excellent t to the stress relaxation
results) and a continuous spectrum (which will provide an
excellent t to the DMTA results) [see Eq. (13)].
67
Thus, the
following expressions were found to describe the increase
of E
0
and E
00
with increase in f (x 2pf)
77
:
E
0
x E
1
x
_
1
0
DEs sinxsds (16)
E
00
x x
_
1
0
DEs cosxsds (17)
where E
1
is a material constant and E is the viscoelastic
modulus.
Summary. There is a modest number of studies on inu-
encing factors, from which it appears that a signicant
intrinsic parameter is the powder particle size distribu-
tion while test frequency and test temperature are signif-
icant extrinsic factors. Furthermore, there is a plasticizing
effect on tan d and there is a dearth of work on
modeling.
Rheological properties
Variation of viscosity of cement with time. The primary
rheological parameter is the variation of the viscosity of the
polymerizing cement with time. Four approaches have been
taken for such determination.
In the rst, a rotational or capillary extrusion rheo-
meter/viscometer was used.
7881
With this set-up, the vari-
ation of the pressure gradient (P) with t
m
is obtained,
which leads to the variation of the apparent or false viscos-
ity of the cement (l) through use of the Hagen-Poiseuille
equation:
l
pPR
4
8LQ
(18)
where R is the radius of the capillary/die, L is the length of
the capillary, and Q is the volumetric ow rate of the
cement dough (or the rate at which the cement dough is
injected into the capillary). A typical l-time plot is given in
Figure 7(a).
FIGURE 7. (a) Typical results for false or apparent viscosity of a
curing PMMA bone cement dough, obtained at ambient temperature
of 22

C, and a shear rate of 0.5 s

1
. (b) Typical results for complex
viscosity of a curing PMMA bone cement dough, obtained at ambient
temperature of 22

C.
182 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
In the second approach, the viscosity tests were per-
formed using a commercially available device that basically
involved placing the cement dough in a cartridge and con-
tinuously recording the force needed to immerse a cone-
shaped measuring tool (diameter and surface area 28
mm and 610 mm
2
, respectively), at a dened speed (typi-
cally, 0.03 mm/s), into the dough as it polymerizes. In the
present review, we shall designate the plot of the results
obtained using this device as the force viscosity-versus-t
m
plot.
82,83
In the third approach, the cement dough was placed into
the cup of a rheometer that has a cup-and-plate congura-
tion (or on the lower plate of a rheometer that has a plate-
plate conguration), bringing the plate or top plate to touch
the dough, and then performing the test in a dynamic
oscillation mode (i.e., the plate or top plate is subjected to a
displacement (typically, 6 10 lm) at a xed frequency (typ-
ically, 15 Hz).
7275,8486
) The rheometer is a force-reso-
nance analyzer which means that the peak compressive
force transferred from the curing cement (F) to the plate is
tracked by a force transducer, as a function of t
m
. The F
t
m
results are exported to a computer containing a soft-
ware that converts these results to complex viscosity (g*)-
versus-t
m
results.
8486
Typical g*-t
m
results are given in
Figure 7(b).
The fourth approach involved using a coaxial cylinder-
type self-sensing rheometer that is comprised of an oscillat-
ing spindle that is inserted in the cement dough and is driven
by a computer-controlled electromagnetic actuator.
87
The
actuator uses a model to obtain both the displacement and
the torque without the use of sensors, from which the
storage modulus (G
0
) and the loss modulus (G
00
) of the curing
are obtained. A software package in the computer converts
these moduli to g* using the following relationships:
g
0
G
00
=x; g
00
G
0
=x; g g
0
ig
00
(19)
The issue of comparability in the viscosity-t
m
results
based on the viscosity measurement method used has
received very limited attention, with one study being on
CMW3.
84
For this cement, at a given value of t
m
, it was
found that g* is markedly higher than l, a nding that is in
consonance with the Cox-Merz rules.
88
A caveat should be
attached to this result because, g* was experimentally
determined in one study
84
but the corresponding l result
was taken from another study/report.
17
Categorization of cement brands. Results of the variation
of l with t
m
has been used to categorize commercially avail-
able cements into low-viscosity cements (for example,
Zimmer LVC; l 1 kPa s at t
m
5 min); medium-viscos-
ity cements (for example, Surgical Simplex P; l 5 kPa s
at t
m
5 min) and high-viscosity cements (for example,
Palacos R; l 14 kPa s at t
m
5 min).
89
Explanation of viscosity-time prole. When g* is deter-
mined, it is seen that, with increase in t
m
, there is an initial
steady rise, followed by a nal rapid rise. The former stage
is due to swelling and dissolution of the polymer beads in
the liquid monomer as the powder is wetted by the mono-
mer, while the latter stage is due to the polymerization
reaction.
84,90
Inuencing factors. The importance of the composition of
the powder beads in a PMMA bone cement is exemplied
by the clear differences in the force viscosity-versus-t
results for two commercially available PMMA bone cements;
specically, a tobramycin-loaded cement (Simplex with
Tobramycin) showed a lower initial value of median force
viscosity than a gentamicin-loaded cement (Palacos RG).
In Simplex with Tobramycin, the beads are of MMA-styrene
copolymer and, thus, are more hydrophobic (take longer to
dissolve in the liquid monomer) than the MMA-MA beads in
Palacos RG.
83
On the basis of the force viscosity-versus-time results
obtained from three variants of a commercially available
gentamicin-loaded PMMA bone cement (Refobacin Palacos
R, Palacos RG, and Refobacin Bone Cement), it was sug-
gested that, for a gentamicin-loaded cement, the median
force viscosity, at a given t
m
, may be inuenced by varia-
tion in the polymer/copolymer particle size ratio.
82
Appa-
rent contradictions in the force viscosity-versus-t
m
results
for Palacos RG and Refobacin Bone Cement from the same
research group
82,83
point to the need for further study of
the issue of the signicance of variation in composition of a
given gentamicin-loaded PMMA bone cement vis a vis curing
cement properties.
The fact that cements belong to the same viscosity cate-
gorization group (i.e., high-viscosity, medium-viscosity or
low-viscosity) does not necessarily mean that their g*-t
m
proles are of the same form. Thus, differences were noted
in this prole for Cemex Isoplastic, CMW1, and Palacos R,
each of which is a high-viscosity brand.
73
Specically, dur-
ing the early stages of curing, Cemex Isoplastic was the
most viscous, and Palacos R the least viscous, with CMW1
becoming the most viscous in the latter stages of curing.
73
For an experimental cement, whose radiopacity was pro-
vided by ZrO
2
(530%), for a given amount of ZrO
2
, l was
signicantly higher when cross-linked PMMA nanospheres
were added to the powder than when cross-linked PMMA
macrospheres were added. This was attributed to (1) the
higher surface area of the nanospheres, which translates to
high diffusion of the liquid monomer
81
; and (2) increase in
the volume fraction of particles in the powder mixture.
91
Each of three experimental cements designed for use in
VP and BKP (radiopacier: 10%BaS0
4
; radiopacier: 10%
BaSO
4
5% ciprooxacin (CFX); and radiopacier: 10%
BaS0
4
3% CFX 3% vancomycin) displayed g*-t
m
char-
acteristics, in the initial stage, that are very similar to those
for a commercially available PMMA bone cement (Osteopal
G) at t
m
< $6 min.
74
Because of delayed setting, however,
g* remains constant and low for much longer (up to t
m
>
$11 min) before a nal sharp rise in the case of the experi-
mental cements.
74
The inuence of radiopacier on the g*-t prole of an
ABC depends on the section of the curve being considered.
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Thus, for an experimental cement, for t
m
$15 min, the
g*-t curve was practically the same when the radiopacier
was 10 wt % BaSO
4
particles in the powder as when any
one of three other radiopaciers (10 wt % SrHA, 10 wt %
SrHA treated with MMA (SrHA-m), and 20 wt % SrHA-m)
was blended into the powder.
75
For t
m
> $15 min, there
were similarities and differences seen in the plots for the
four cements. For the 10 wt % BaSO
4
-containing cement,
there was a very sharp rise in g* (which corresponds to an
increase in polymerization). For the 20 wt % SrHA-m-con-
taining cement, there was a slow rise in g* for 10 min, fol-
lowed by a sharp rise, whereas for each of the other two
cements, g* rose at a moderate rate.
75
Reducing the modulus of a PMMA cement for use in VP
or BKP, by adding N-methyl-pyrrolidone to the liquid mono-
mer (5060%), led to a signicant reduction in the poly-
merization rate, as manifest through a signicant reduction
in g*, at any given t
m
.
80
This trend is attractive in that it
shows an approach that may be taken to widen the window
for injecting the cement into the cannula during VP or BKP.
The importance of the dispersal of an additive in the
cement on the viscosity-time characteristics is illustrated by
results from two variants of an experimental cement, one in
which a clay (2% sodium montmorillonite (SMMT) or 2%
organophilic montmorillonite (OMMT)) was blended with
the powder and the other in which the clay was added to
the liquid monomer. In each variant, there was an increase
in g*, at a given t
m
(relative to case for the plain cement),
with this trend being likely due to the clay increasing the
shear modulus of the cement.
85
More importantly, however,
at a given t
m
, a cement in which OMMT was added to the
liquid monomer showed the highest g*, this trend being
attributed to the clay in this cement being well dispersed.
85
For Palacos R, a decrease in the temperature at which
the cement was stored prior to mixing (T
st
) led to a
decrease in l throughout the polymerization period.
79
Alter-
natively, for this cement, the time taken to reach a specied
viscosity increases with increase in T
st
.
79
These trends may
be explained in terms of the fact that lowering of T
st
leads
to delay of generation of free radicals, which translates to
delaying the initiation of the polymerization process.
79
The time taken to reach a specied viscosity decreases
with increase in the temperature of the room in which the
cement is mixed (T
a
).
90
This observation highlights the need
to ensure that, during a cemented TJR procedure, the tem-
perature of the operating room does not uctuate at the
early stages; that is, during the time interval between
cement preparation and hardening of the cement in the
bone bed.
The method used to mix the cement is an important
inuencing factor. Thus, for each of three commercially
available PMMA bone cements (Antibiotic Simplex, DP-Pour,
and Vertebroplastic), mean l, at a given time (t
m
), was
markedly higher when the cement was hand/manually
mixed compared to when it was mixed using an oscillating
machine (shaking stroke amplitude and frequency 20 mm
and 10 Hz, respectively).
78
This trend was attributed to the
pseudoplastic behavior of PMMA bone cements; that is, the
thinning of the cement when subjected to a large shear strain
as is experienced during oscillatory mixing. Furthermore, at a
given t, the coefcient of variation (standard deviation/
mean) of the l results, which is a measure of their reprodu-
cibility, was markedly lower when oscillatory mixing was
used compared with when hand mixing was used.
78
This was
attributed to the fact that the oscillatory mixing conditions
were controlled (xed shaker stroke amplitude and fre-
quency) whereas the hand mixing conditions were not.
78
For a given cement, for a given t
m
, l decreases with
increase in shear rate, c, in a manner describable by the fol-
lowing power equation
92
l a
t
t
s
_ _
b
_ _

c
c
s
_ _
ct=tsd
(20)
where t
s
is a characteristic time, c
s
is a characteristic shear
rate, and a, b, c, and d are constants, all of whose values are
determined from the t between the experimental data and
Eq. (20). For example, for Surgical Simplex P, for 3.0 min
t
m
5.0 min and 0.4 s
1
c 100 s
1
, the best-t values
of the constants in Eq. (20) were found to be: t
s
1.0 min,
c
s
1.0 s
1
, a 590.0 Pa s, b 1048.8 Pa s, c
0.026, and d 0.290.
92,93
This observation of l decreas-
ing with increasing c, which shows that curing cement is a
pseudoplastic material, has clinical relevance in that it could
be used by orthopaedic surgeons in making a decision as to
whether to insert the cement dough into the prepared bone
bed rapidly or slowing. Any such decision, however, should
also take cognizance of the inuence of delivery speed on
cement interdigitation; specically, interdigitation is facili-
tated by slow delivery of the cement dough. This same
trend, namely, decrease of viscosity with increase in shear
rate, at given value of t, was seen when g* results were
used.
86
Summary. There is a sizeable literature on the inuence of
an assortment of intrinsic factors, such as cement composi-
tion, and extrinsic factors, such as cement mixing method,
on the viscosity-time prole of a PMMA bone cement. The
ensuing databank of results allows the identication of fac-
tors to be used in order to obtain a desired prole of vis-
cosity-time following commencement of cement mixture.
Relationship between handling, viscosity,
and damping parameters
Three handling parameters that are related to the viscosity-
versus-t
m
prole are: (1) the time of onset of cure
(t
ons
),
72,74
(2) the critical cure rate (CCR),
84
and (3) the
cure time (t
cur
).
73
Both t
ons
and CCR were estimated from
the g*-t
m
results. t
ons
was dened as the time at which
there was a signicant increase in g*
84
or as the time at
which the intersection of the linear ts of the initial and
nal zones in an g*-t
m
plot occurs.
72
From a phenomeno-
logical perspective, t
ons
may be regarded as the time at
which the process that accounts for the viscosity of the
cement changes from dissolution of the PMMA beads in the
liquid monomer to polymerization.
72
CCR was dened as
184 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
the value of the time derivative of the best-t equation to
the initial stage of the g*-t
m
results with t
m
being put equal
to t
ons
in that derivative.
84
For example, for CMW3, the
aforementioned best-t equation was found to be
84
:
g 1713:655t
m
1:691
for 0 t
m
8:5 min r 0:998
(21)
Since t
ons
was found to be 12.03 min,
84
CCR 1.62
10
4
Pa s min
1
.
For PMMA bone cements for use in TJRs, both t
ons
and
CCR increased signicantly with increase in both the rela-
tive amount of small-sized PMMA beads (mean diameter, d,
between 0 and 40 lm) in the cements powder (we desig-
nate this ratio, a) and the relative amount of large-sized
PMMA beads (d > 75 lm) in the cements powder (we des-
ignate this ratio, b).
84
This was explained as follows: during
polymerization, the small-sized PMMA beads are completely
dissolved in the liquid monomer, while the dissolution of
the large-sized PMMA beads takes a longer time; thus, high
a leads to high CCR and high b leads to high t
ons
.
84
Bead size is also important for PMMA bone cements for
use in VP and BKP. For one experimental formulation of such
a cement, an increase in the proportion of small PMMA beads
(mean diameter 70 lm) to large ones (mean diameter
118 lm) (we designate this ratio, H, in wt/wt %) led to an
increase in t
ons
.
72
For example, t
ons
was 7 min and $13 min
for H 0.11 and 9.00, respectively.
72
This trend was attrib-
uted to the dissolution of the beads (and, hence, the onset of
polymerization) appearing earlier as H increases
72
For experimental cements designed for use in VP and
BKP, there is a linear relationship between t
ons
and setting
time (as determined using the international materials test-
ing standard, ISO 5833).
72
This relationship points to,
among other things, the potential of rapid estimation of t
ons
via the testing standard because there is widespread famili-
arity with the standard.
From results of the variation of G
0
, G
00
, and tan d with t
m
,
t
cur
was obtained as the time at which these parameters
reach a maximum, minimum, and minimum, respectively.
73
With this approach, for Cemex Isoplastc, CMW1, and Palacos
R, t
cur
decreased by $50% when the temperature at which
the measurements were made was increased from 25

C to
37

C,
73
which reiterated the point that cement curing is a
thermally activated (Arrhenius) process.
62
Strain rate dependence of mechanical properties
With increase in the strain rate used in a test (e
:
), marked
increases in various mechanical properties of different
cement brands have been reported. Specically, for (1)
shear strength increased by 30% when e
:
was increased
from 0.001 s
1
to 0.1 s
194
; (2) compressive strength of a
commercially available antibiotic-loaded PMMA bone
cement (AKZ) increased by 50% and 67% when the speci-
mens were loaded at 1.8 s
1
and 5.2 s
1
, respectively
(increase relative to value obtained when specimens were
loaded quasi-statically)
95
; and (3) for a carbon ber-rein-
forced PMMA bone cement, compressive strength increased
27% when e
:
was increased from 6.2 10
4
s
1
to 1.24
10
2
s
1
.
96
These ndings,
9496
which underscore the fact that
PMMA bone cement is a viscoelastic material, highlight the
need to state, in comparisons of results from various litera-
ture studies of a specied mechanical property for a given
cement, the loading rates used in these studies.
CALCIUM PHOSPHATE CEMENTS
Viscosity-time and damping proles
Method of determination. For viscosity determination,
two types of rheometers have been used. One is a capillary
rheometer, which leads to determination of false or appa-
rent viscosity (l).
78,97100
The other is a cone-and-plate sys-
tem, in which a predetermined shear rate-versus-time wave
is imposed on the CPC slurry, allowing determination of
shear stress-versus-shear strain rate curve and, hence, if
desired, dynamic viscosity (g*)-versus-t
m
prole.
101103
An adjunctive test, performed in a cone-and-plate rhe-
ometer, involves applying a small-amplitude sinusoidal oscil-
lation strain to the CPC slurry, and then using the resulting
shear stress and shear strain values to determine G
0
and G
00
.
101103
Characteristic features. At a given combination of condi-
tions in a dynamic viscosity test (i.e., for a xed combination
of applied frequency and strain), G
0
, G
00
, and g all increase
with increase in t
m
, in accordance with the following
power-law relationship
S a expbt
m
; (22)
where S is a given rheometric parameter (that is, G
0
, G
00
, or
g*), a represents the initial value of the parameter (i.e., a
value that denotes the state of the grains in the CPC slurry
prior to commencement of the setting reaction), and b is
related to the rate of the setting reaction.
103
For example,
using G
0
results for a slurry of a CPC (powder: equimolar
TTCP (mean particle diameter: 13.3 lm) and dicalcium
phosphate anhydrous (DCPA; mean particle diameter: 0.63
lm); liquid: deionized water), the best-t values of a and b
were found to be 1621 Pa and 6.45 10
3
s
1
, respec-
tively, when the slurry powder-to-liquid ratio (PLR) and test
temperature were 2.00 g mL
1
and 37

C, respectively.
103
The existence of a hysteresis loop in the shear stress-
versus-shear rate prole of a CPC, as obtained from viscos-
ity tests (Figure 8), demonstrates that the slurry is a thixo-
tropic material.
100,103
At a given setting time, there is an
overshoot of the shear stress in the initial stage of the vis-
cosity-versus-shear rate prole when shear rate was less
than 1.5 s
1
(Figure 8), indicating the existence of a yield
stress in the slurry.
103
A CPC slurry is a non-Newtonian
uid that displays shear thinning, evidenced by the facts
that (1) its viscosity decreases with increase in shear rate
(after a critical shear rate, such as 1.5 s
1103
or 15.0 s
1100
;
(2) G
0
, G
00
, and g* all decrease with increase in the shear
strain used in a dynamic viscosity test, for a given test fre-
quency (x)
103
; 3) at x greater than a critical value (for
example, 0.2 rad s
1103
), g* decreased with increase in x
103
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 185
and (4) at x greater than a critical value (for example, 0.7
rad s
1103
), both G
0
, G
00
decreased with increase in x.
103
Inuencing factors. The viscosity of a CPC slurry is sensi-
tive to the incorporation of additives to the basic constitu-
ents of the powder. (Basic constituents are herein dened
to be the various CaP compounds.) Thus, at a given shear
rate, the viscosity of an experimental CPC (powder: 50 wt/
wt % amorphous calcium phosphate (ACP) 50 wt/wt %
DCPD; median powder particle diameter: 3.0 lm; liquid:
deionized water; PLR 2.0 g mL
1
) decreased signicantly
with increase in the amount of strontium carbonate (SrCO
3
;
median diameter; 2.5 lm) added to the cement powder,
over the SrCO
3
content range of 020 wt/wt %.
98
For exam-
ple, at 1 10
2
s
1
, viscosity decreased by a factor of 10
when the content was increased from 0 to 12 wt/wt %.
98
This trend, together with other results (radiopacity, inject-
ability, compressive strength, and pore distribution) sug-
gests that this CPC containing 12 wt/wt % SrCO
3
may have
promise for use in VP and BKP.
98
The particle size in the powder suspension of a CPC
exerts a marked inuence on the viscosity of its slurry. For
example, at a given PLR, the viscosity of a slurry of a b-TCP
CPC increased with increase in the time over which the
powder was milled in a planetary mill, t
m
(3 t
m

30 min), with this trend being a result of the decrease in par-

ticle size in the powder suspension with increase in t
m
.
102
PLR is, arguably, one of the most important inuencing
factors on viscoelastic properties of a CPC slurry. At a given
hydration time, G
0
, G
00
, and g* of the slurry of each of two
experimental CPCs (CPC1: powder: 1M TTCP (median dia-
meter: 0.39 lm18.33 lm) 1M DCPA (median diameter:
8.38 lm21.70 lm) 3.0 wt/wt % hydroxyapatite (HA)
(diameter: 1020 lm); liquid: deionized water; and CPC2:
b-TCP powder deionized water, xanthan, or sodium poly-
acrylate) all increased signicantly with increase in PLR of
the CPC (1.67 PLR 2.50).
102
This trend was attributed
to decrease in particle-particle interaction with decrease in
PLR.
102
The signicance of PLR is also reected in its effect
on the size of the thixotropy loop (in the shear stress-shear
rate plot), with this size decreasing from large (at PLR
2.00 or 2.50 g mL
1
) to practically zero (at PLR 1.67 g
mL
1
) in the case of a CPC in which the powder was pre-
pared by mixing b-cyclodextrin, ACP, and DCPD.
100
At a given PLR, the viscosity of the slurry is inuenced
by the viscosity of the aqueous medium used to prepare the
slurry and the amount of the medium. For example, in
the case of CPC2, using xanthan or sodium polyacrylate as
the medium led to signicant increase or signicant
decrease in viscosity, respectively, relative to when deion-
ized water was used.
102
Furthermore, the viscosity
increased with increase in the content of some additives
(xanthan; 0.1% and 0.2 vol %)
102
but decreased with
increase in the content of some other additive (sodium poly-
acrylate; 0.5 vol % and 1.0 vol %).
102
Xanthan promotes
occulation, which, it is suggested, is brought about by the
adsorption of one polymer molecule onto more than one
suspended particle, bridging the two particles together, and
forming a stable single bloc.
104
In contrast, sodium polya-
crylate, being a dispersing modier, causes an increase in
the electrostatic repulsion forces between the particles.
105
The details of the inuence of cement mixing method on
viscosity results depends on the CPC considered. Thus, for
one commercially available CPC (Biopex), mean l, at a given
t, is, essentially, unchanged when the cement was hand/
manually mixed compared to when it was mixed using an
oscillating machine (shaking stroke amplitude and fre-
quency 20 mm and 10 Hz, respectively).
78
In contrast, for
another commercially available CPC (chronOS Inject), the
mean l, at a given t, was signicantly lower when the
cement was mixed using an oscillating machine (shaking
stroke amplitude and frequency 20 mm and 10 Hz,
respectively) compared to when it was hand mixed.
78
The
latter trend was attributed to the pseudoplastic behavior of
PMMA bone cements; that is, the thinning of the cement
when subjected to a large shear strain as is experienced
during oscillatory mixing. For each of these two cements,
however, at a given t, the coefcient of variation of the l
results was lower when oscillatory mixing was used com-
pared to when hand mixing was used.
78
This, it was postu-
lated, was a consequence of the fact that the oscillatory mix-
ing conditions (shaker amplitude and frequency) were
controllable, whereas the hand mixing conditions were
not.
78
G
0
of the slurry of an experimental CPC (powder: equi-
molar of TTCP (median particle diameter: 13.3 lm) and
DCPA (median particle diameter: 0.63 lm) 3 wt/wt %
HA (particle diameter: 1020 nm); liquid: deionized water;
PLR 2.5 g mL
1
)) increased with increase in the tempera-
ture of the slurry (T
sl
) (15

C T
sl
37

C),
103
consistent
with setting of the CPC slurry being an Arrhenius process.
62
FIGURE 8. Variation of shear stress with shear strain rate for a CPC
slurry after 30 s of setting (CPC powder mixed with deionized water
using a powder-to-liquid ratio of 2.25), obtained using dynamic rheo-
logical testing at 37

C. (Reprinted from Biomaterials, volume 27, C.

Liu, H. Shao, F. Chen, and H. Zheng, Rheological properties of con-
centrated aqueous injectable calcium phosphate slurry, pages 5003-
5013, copyright (2006), with permission from Elsevier).
186 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS
Summary. The methods used for characterizing the visco-
elastic properties of CPCs are the same as those used for
ABCs. More research attention has been given to the inu-
ence of extrinsic factors on the viscoelastic properties of
CPC than to the inuence of intrinsic factors. Studies on
modeling any viscoelastic property of a CPC are lacking.
AREAS FOR FUTURE STUDY
Five areas for consideration for future study are
presented.
The rst is to perform detailed systematic parametric
studies such as (1) inuence of an antibiotic on the creep
deformation of a PMMA bone cement, obtained using fully
constrained specimens subjected to dynamic loading; and
(2) the inuence of intrabatch and interbatch variability on
the dynamic viscosity-versus-time and damping properties
(storage modulus-versus-t, loss modulus-versus-t, and loss
factor-versus-t) of a given commercially available acrylic
bone cement used for TJRs.
The second area is to develop testing standards for
determining various viscoelastic properties of ABCs, CPCs,
and CSCs. A principal aspect of each of these standards
should be a detailed denition of the combination of loading
mode and environmental conditions that simulate clinical
conditions. A complementary project should be establish-
ment of minimum and maximum levels of a given visco-
elastic property, such as creep rate, that will render the
cement useful for clinical application. For example, it was
suggested that, for PMMA bone cements to be used in VP,
the viscosity of the dough upon insertion into the fractured
vertebral body should be in the range of 100200 Pa s,
which is achievable with a shear rate of 40 s
1
.
106
The third area for future research is to enhance the data-
base on viscoelastic properties of IBCs that, to date, have
received little attention. Three such types of cements are rec-
ognized. The rst is the new generation of ABCs that address
one or more of the long list of drawbacks of commercially
available ABCs (in the literature, this new generation of
cements has been designated alternative acrylic bone
cements).
107
Recent examples of alternative acrylic bone
cements are (1) a cement that contains a methacrylate whose
lower toxicity is lower than that of MMA; specically, the
principal liquid constituents for the new cement are 2-ethyl-
hexyl methacrylate (EHMA) and trimethylolpropane while
poly(EHMA/cyclohexyl methacrylate) beads is the principal
powder component
108
; (2) a cement comprising copolymers
of MMA and lauryl methacrylate, in the ratio 1:1 v/v, was
considered suitable for use in BKP
109
; (3) a cement compris-
ing a new class of radiopaque monomer using a copolymer
based on MMA and GMA that is made radiopaque by the
epoxide ring opening of the GMA, followed by the covalent
attachment of elemental iodine
110
; (4) a PMMA cement rein-
forced with variable-diameter ZrO
2
bers
111
; (5) a PMMA
cement that has reduced toxicity and added osteoconductivity
through the incorporation of N-acetyl cysteine in the liquid
monomer
112
; and (6) a PMMA that is reinforced with TiO
2
-
SrO nanotubes that are functionalized using a monomeric
coupling agent (methacrylic acid).
113
The problem of reduced efcacy of antibiotic-loaded
PMMA bone cements (ALBCs) arising from increasing resist-
ance of the relevant microorganisms (such as Staphylococcus
aureus) to the antibiotics that are commonly used in ALBCs
(such as gentamicin sulfate) has been noted.
114
This situa-
tion has created an opportunity for exploring the suitability
of incorporating new classes of antibiotics into ALBCs, lead-
ing to a new generation of commercially available ALBCs.
One such antibiotic is daptomycin, a cyclic lipopeptide that
has been shown to be very effective against a number of
microorganisms in various patient populations, such as dif-
cult bone and joint infections caused by methicillin-resistant
Staphylococcus epidermidis.
115
Thus, an example of this new
generation of ALBCs (which constitutes the second group of
IBCs for future study) is a daptomycin-loaded PMMA bone
cement, for which some in vitro properties have been
determined.
116
The third group of IBCs are those that do not have the
drawbacks of cements that are currently being used for VP
and BKP; for example, modulus and strength being signi-
cantly greater than the corresponding values for osteopor-
otic cancellous bone (PMMA bone cements) and poor inject-
ability (CaP cements). Recent examples of this new
generation of IBCs that may nd use in VP and/or BKP are
(1) a bioactive calcium aluminate cement
117
; (2) a reduced-
modulus PMMA bone cement achieved through manual mix-
ing of a 10% solution of hydroxypropylmethyl cellulose
(4550% aqueous volume fraction) with the PMMA
118
; (3)
a two-solution PMMA cement (each pair of solutions con-
sisting of prepolymerized PMMA powder (80,000 g/mol)
dissolved in MMA, with BPO added to one solution to serve
as initiator of the free radical polymerization reaction and
DMPT added to the other to serve as activator/accelerator
of that reaction) that is modied by incorporation of either
ZrO
2
microspheres or nanospheres (20 wt %)
81
; (4) an
iron-modied a-tricalcium phosphate-CaSO
4
dihydrate
cement
119
; (5) a Sr-containing carbonate apatite cement, in
which the powder constituents are calcium hydrengeno-
phosphate dihydrate, CaO, and SrCO
3
, and the liquid constit-
uent is 0.75M ammonium phosphate
120
; (6) a partially
resorbable composite of CaSO
4
and HA
121
; and (7) an alumi-
num-free, zinc-based glass polyalkenoate cement.
122
The fourth area for future research is to expand the
database on viscoelastic properties of IBCs that, to date,
have not been studied; namely, CSCs for use in VP and BKP,
lamentary composite materials for use in VP and BKP,
and injectable bone void llers/bone graft substitutes.
Recent examples of the materials that may nd use in the
last-mentioned applications include (1) a calcium sulfate-HA
composite
123
; (2) CaCO
3
-CaP cement, comprising at least
40 wt/wt % CaCO
3
in the powder
124
; (3) a CaP-20% mass
fraction chitosan composite
125
; (4) a cement whose constit-
uents are CaP, glycerol (a liquid phase carrier), and polyvi-
nyl alcohol (a biodegradable hydrogel)
126
; and (5) a com-
posite of CaP (equimolar TTCP and DCPA) and CSC
(CaSO
4
.0.5H
2
O)).
127
The fth area is to perform studies on modeling the
creep and stress relaxation of newly developed IBCs. For
REVIEW ARTICLE
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 187
this, results generated from studies conducted in the afore-
mentioned third and fourth areas should be utilized.
SUMMARY
Some of the main points revealed in this review are:
1. The volume of the literature on viscoelastic properties of
injectable bone cements for use in orthopaedic appli-
cations may be characterized as modest, with the pre-
ponderance of the work being on creep, damping, and
viscosity-time characteristics of plain acrylic bone
cements for use in anchoring total joint replacements.
2. Although there have been many studies on the inuence
of a host of variables on various creep performance
measures of acrylic bone cements, the presence of con-
founding variables in many of these studies makes it dif-
cult to make denitive statements on the nature of
most of these inuences.
3. For an acrylic bone cement, a number of important con-
tributions have made in modeling its creep and a wide
collection of empirical relationships have been obtained
for both its creep and stress relaxation.
4. For an acrylic bone cement, powder particle size distri-
bution, test temperature, and test frequency are some of
the variables that appear to exert marked inuence on
its damping behavior.
5. For an acrylic bone cement, there is indication that incor-
porating certain additives has a clear inuence on the
viscosity of the curing cement.
6. The literature is either decient or lacking in studies of
viscoelastic properties of a number of IBCs, such as the
new generation of PMMA bone cements that are
designed to supplant commercially available ones, antibi-
otic-loaded PMMA bone cements, calcium phosphate-
based cements, calcium sulfate-based cements, and bone
void llers/bone graft substitutes.
7. As a result of observations given in items (2), (4), (5),
and (6) above, opportunities abound for future research
in the eld of viscoelastic properties of IBCs for ortho-
paedic applications, with examples being determination
of the inuence of mixing method on damping properties
of ABCs for use in total joint replacements, development
of standards for the determination of viscosity of calcium
phosphate cements for use in balloon kyphoplasty, and
modeling of the stress relaxation of calcium sulfate
cements.
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