Download - Viscoelastic Properties of Inject Able Bone Cements for Orthopeadic Applications State of the Art Review

Review

Viscoelastic properties of injectable bone cements for orthopaedicapplications: 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 fillers/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 influence 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 profile 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 field of viscoelastic proper-

ties of IBCs are described. VC 2011 Wiley Periodicals, Inc. J Biomed

Mater Res Part B: Appl Biomater 98B: 171–191, 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, filling of a bonecyst). On the basis of chemistry, IBCs may be classified asacrylic bone cements (ABCs), calcium phosphate-basedcements (CPCs), calcium sulfate-based cements (CSCs), andfilamentary composite materials. Alternatively, on the basisof the nature of the orthopaedic application, IBCs may begrouped into those for high load-bearing applications(ABCs), medium load-bearing applications (ABCs, someCPCs, and some CSCs), and low load-bearing applications(some CPCs and CSCs).

For the past 50 or so years, ABCs specifically, poly(methyl methacrylate) (PMMA) bone cements have beenwidely used as the anchoring/grouting agent in total hipjoint replacements (THJRs) and total knee joint replace-ments (TKJRs)1,2 as well as in a large variety of other jointreplacements (TJRs), such as those of the ankle,3 elbow,4

the proximal interphalangeal joint,5 and shoulder.6 In acemented TJR, the main functions of the cement are to im-mobilize the implant, transfer body weight and service loadsfrom 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 surgicalmethods for treating osteoporosis-induced pathologicalfractures of the vertebral body (vertebral compressivefractures).8–10 The essence of these methods involves injec-tion of a dough of an IBC through a cannula and under fluo-roscopic guidance either directly into the fractured verte-bral body (VP) or into a cavity created in the fracturedvertebral body by the inflation of an inflatable balloon tamp(BKP).8–10 The goals of these methods are to augment thefractured vertebral body (VP and BKP),8–10 stabilize it (VPand BKP),8–10 and/or restore it to as much of its normalheight and functional state as possible (BKP).8–10

CPCs and CSCs are widely used as injectable bone voidfillers/bone graft substitutes, in which they are injected intosurgically created osseous defects (for example, treatmentof complicated bone cysts in children11) or bone defects cre-ated secondary to traumatic injury to the bone (for example,augmentation of the fixation of displaced intra-articular cal-caneal fractures.12) In the US, there are �900,000 hospital-izations per year to treat fractures13 and �800,000 bonegraft procedures are performed each year.14

For the purposes of the present review, viscoelasticproperties of an IBC refer to creep, stress relaxation, damp-ing, the profile of the viscosity-versus time following

Correspondence to: G. Lewis; e-mail: [email protected]

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 areimportant for the following reasons. First, in the case ofcemented TJRs, the viscosity of the cement dough at thetime of its insertion into the prepared bone bed exerts a sig-nificant influence on the nature and extent of interdigitationof the cement into the contiguous bone, which, in turn,affects the integrity of the cement-bone interface.15 Thisinterface has been identified as one of the three weak zonesin a cemented TJR (the others being the cement mantleitself and the cement-implant interface) and its integrity ispostulated to have a significant impact on the in vivo lon-gevity of a TJR.16 Arguably, the most prominent differenceamong the myriad commercially available PMMA bonecement brands is in the viscosity of the polymerizingcement-versus-mixing time profile.17 Second, it has beensuggested that, in a cemented TJR, a small amount ofcement creep may, in fact, be beneficial, especially in the im-mediate post-implantation period.15 For example, a polished,tapered, collar-less femoral stem of a THJR relies on acertain 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 theimplant and increasing the in vivo longevity of the TJR.15

Furthermore, cement creep may cause stresses in thecement 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 tensilestrength.7 Also, it has been suggested that, in a cementedTJR, cement creep may be beneficial in helping to relieveresidual 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 amountof cement creep is undesirable as it leads or contributes toloosening and/or subsidence of the implant.19 Third, as faras use of IBCs for applications such as VP and BKP is con-cerned, the viscosity of the polymerizing cement-versus-mix-ing time profile is directly correlated with the profile of thevariation of the pressure (force) required to inject thecement paste through the cannula with time of injection. Atany time of injection, one component of that pressure isthat required to overcome the yield strength of the cementpaste and to initiate flow of the cement while the othercomponent is the pressure required to maintain the flowof the cement dough/slurry. This latter component isdirectly related to the viscosity of the cement slurry. Thecement viscosity is important from another perspective;namely, upon injection into either the fractured vertebralbody (VP) or the void created in the fractured vertebralbody by the bone tamp (BKP), the viscosity of the cementdough must be low enough to allow penetration throughthe cancellous bone but not to permit extravasation, whichis a serious complication.20 The aforementioned points indi-cate that the cement’s viscosity-mixing time profile ulti-mately affects both the feasibility and the outcome of VPand BKP.20

Over the years, a number of reviews of the literature onIBCs have appeared but they are limited in a number ofrespects as far as the viscoelastic properties of these materi-als are concerned. First, in reviews that covered a widerange of properties of ABCs, such as those by Lewis,7 Sahaand Pal,21 Hasenwinkel,22 Serbetci et al.,23 Deb,24 andBoesel,25 treatment of viscoelastic properties was eithervery brief and incomplete7,21–23,25 or absent.24 Second, therehas been only one review that focused on viscoelastic prop-erties of ABCs but it only covered the literature on apparentviscosity-versus-mixing time profiles and was publishednearly 30 years ago.17 Third, a number of reviews haveappeared on the properties of CPCs and CSCs that havebeen used or have the potential for use in VP and BKP,26–31

but viscoelastic properties were not discussed in any ofthem. Fourth, the present author is unaware of any reviewof viscoelastic properties of FCMs, as used in VP and BKP.Fifth, viscoelastic properties were not included in reviewsof properties of bone void fillers/bone graft substitutes.32–34

The purposes of the present contribution were to pres-ent a comprehensive review of the literature on all theviscoelastic properties of all chemistries of IBCs and to high-light areas for future research in this field. In support of thefirst-mentioned purpose, a detailed search was conducted ofrelevant databases (such as MEDLINEV

R

/PubMed andPubMed Central), science subjects-specific search engines(such as SCIRUSV

R

) and the table of contents of relevant keyjournals (such as Journal of Biomedical Materials ResearchPart B: Applied Biomaterials, Biomaterials, and Journal ofMaterials Science: Materials in Medicine) for relevant peer-reviewed articles published, over the period 1975-date, inEnglish as well as in other languages. Furthermore, thereferences list of each article, obtained from this search,was manually examined to identify additional relevantarticles. The review is organized into four parts, with thesebeing containing, in order, reviews of the literature on ABCs,reviews of the literature on CPCs, discussion of futureresearch topics, and a summary of the most salient pointsmade in the work.

ACRYLIC BONE CEMENT

Creep deformationSpecimen constraint and loading conditions in experi-mental tests. In a creep test, a specimen is positioned inthe testing machine (typically, the specimen is enclosed inan environmental chamber) and then subjected to a speci-fied type of loading, with the response of the specimen (typ-ically, its deformation) being continuously monitored untileither the specimen fractures or the test is terminated aftera certain length of time. Two types of specimen constraintshave been used; namely, unconstrained and constrained. Inthe former case, the specimen is unsupported along itssides35–52 while, in the latter case, the specimen is placedbetween a steel outer jacket and a stainless steel innercore, simulating the restraint between the implant andthe cancellous bone in a cemented TJR.53–55 Two types ofloading configurations have been used. One is quasi-static;35–38,40,42–46,49–52 specifically, a 10:1 lever-arm

172 LEWIS VISCOELASTIC PROPERTIES OF INJECTABLE BONE CEMENTS

deadweight set up,36 a cantilever-type testing machine,40 afour-point bend test rig,43 or a three-point bend test rig.49,51

The other is dynamic/cyclical, under load control,39,41,47,48,52–55

with some of the tests run on commercially available universalmaterials 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.53–55

Influencing factorsBrand of commercially available cement. There are

many similarities and differences between the large numberof commercially available PMMA cement brands on the basisof a number of parameters, such as composition (Table I),size of the prepolymerized PMMA beads in the powder (Db),powder particle size distribution, mean powder particlesize, molecular weight of the powder, molecular weight ofthe cured cement, and the profile of change in viscosity ofthe curing cement dough as a function of time followingmixing of the powder and liquid monomer.

For unconstrained specimens aged in water, at 37�C, andthen tested in water, at 37�C, using a pneumatic actuator,(1) the creep strain of laboratory-fabricated Palacos R CumGentamicin specimens was significantly higher than that oflaboratory-fabricated CMW3G specimens; and (2) the creepstrain of Palacos R Cum Gentamicin specimens, fabricatedfrom retrievals following revision of THJRs for aseptic loos-ening of the implant, was significantly lower than whenBoneloc specimens, also fabricated from THHR retrievals,were used.52 It has been suggested that, under certaincircumstances, cement creep, in a cemented TJR, may bebeneficial as it allows adaptation between the implant andthe cement. This postulate is supported by good outcomesin two hospital series in which Boneloc was used to anchorthe femoral component of the Exeter THJR.56 (It is notedthat, with most THJR designs, however, outcomes whenBoneloc was used were very poor, loading to withdrawal ofthe cement from the market in 1994.57)

For constrained specimens, tested in ‘‘body temperature’’under dynamic loading conditions, the dynamic creep strain(ec) values, at 250,000 cycles, were 5500 microstrain and4500 microstrain for Palacos R and CMW1 specimens,respectively.54 The volume-weighted mean values of Db forPalacos R and CMW1 are 55 lm and 44 lm, respectively.54

The trends in these ec results54 appear to be in consonance

with the suggestion that, with increase in Db, there isincrease in the potential for formation of crevice (which actas stress risers), culminating in increased creep deformation.54

The trends in the aforementioned ec results obtainedusing constrained Palacos R and CMW1 specimens underdynamic loading conditions have also been explained on thebasis of difference in two other cement parameters.54 Thefirst was the molecular weight of the cement powder(MWp), with the postulate being that since MWp of PalacosR cement is higher than that for CMW1, the beads of theformer cement swell less and dissolve less, leading to morecrevices in the specimens of the former cement.54 The sec-ond parameter was the difference between MWp and themolecular weight of the cement matrix (MWm) for a given

cement, with this difference affecting the magnitude of thecontact stresses at the matrix-bead interface. These stressesare implicated in debonding of beads from the matrix, cul-minating in creation of microcracks. which, under dynamicloading, may propagate through the specimen. In the case ofPalacos R, MWm < MWp, whereas, for CMW1, MWm >

MWp.54

Under quasi-static compressive stress, the mean creepstrain, 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 thanthat for Zimmer Low ViscosityV

R

specimens.36 At any timeduring a quasi-static four-point bending creep test on uncon-strained specimens, at 37 �C, creep deflection of specimens ofPalacos R cement (‘‘high-viscosity’’ brand) was significantlylarger 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 atrend of decrease in creep resistance with increase in cementviscosity.

For unconstrained specimens in a dynamic compressiontest on specimens immersed in Ringer’s solution, at 37�C,the mean creep strain, after 250,000 cycles, was higher forMendec specimens compared with that for KyphX speci-mens, a trend that was consistent with the trend of higherdensity (q) of KyphX cement (and, hence, lower porosity ofKyphX specimens).47 The significance of q in creep resist-ance of a cement is clarified when the results from speci-mens fabricated from a family of cements with essentiallythe same composition are considered. Thus, for uncon-strained hand-mixed specimens immersed in Ringer’ssolution, at 38.5�C, dynamic compressive strain of CemexIsoplastic (high q) specimens were �16% to �34% lowercompared to the values obtained for Cemex System(medium q) and Cemex RX (low q) specimens.41 It thusappears that low creep strain may be correlated with highcement density.

For unconstrained specimens subjected to quasi-staticthree-point bending, the creep deformation, under similarloading profiles and for a given specimen aging time (inwater, at 37�C), of SmartSet GHV specimens was, onaverage, marginally higher than that of Palacos RþG speci-mens,51 a trend that is not consistent with the fact that thecontent of the gentamicin sulfate, which acts, in essence, asa plasticizer, in the former cement is twice that in the latter.It is noteworthy that there were no significant differences ineither to (which is one of the parameters in the expressionthat relates the creep compliance to the time, as given inthe Kohmrausch creep law58 for the cement) or g0 (which isthe viscosity of the damper-element in a modified Burgers’creep constitutive model of the cement) between the twocements.51 For unconstrained specimens aged in water, at37�C, and then tested in water, at 37�C, using a pneumaticactuator, the creep strain of laboratory-fabricated Palacos RCum Gentamicin specimens was significantly higher thanthat of laboratory-fabricated CMW3G specimens,52 eventhough the gentamicin sulfate content of both cements is

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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH B: APPLIED BIOMATERIALS | JUL 2011 VOL 98B, ISSUE 1 173

the same. These results51,52 indicate that the influence ofgentamicin sulfate on creep performance is unclear.

Composition of experimental cement. Under quasi-static compressive stress, reinforcing PMMA bone cementwith either fibers or particulates led to substantial reduc-tion in a specified creep parameter.35,36,50 These reductions(relative to the value for unreinforced cement specimens)amounted to between �33% and �64% in mean creepstrain after a given time when 2 wt/wt % chopped carbonfibers were added to the cement35,36; and between �37%and �68% decrease in creep compliance at 105 s when ei-ther 10 wt/wt % or 20 wt/wt % hydroxyapatite (HA) pow-der was added to a PMMA bone cement, respectively.50 Forthe carbon fiber-reinforced cement, the trends were attrib-uted to the formation, at a given applied stress, of interporecracks in unreinforced cement specimens and their absencein reinforced cement specimens.36 For the HA-reinforcedcement, the trends were consistent with the fact that, after

a creep test, the reinforced cement specimens showedslower and less complete recovery than the unreinforcedones, which may be attributed to some separation of the HAparticles from the polymer matrix during creep.50

For a hydrophilic, partially degradable and bioactivecement, (1) an increase in the amount of the hydrophilicmonomer led to a significant decrease in the cement’s creeprate45; (2) consistent with a priori expectation, incorpora-tion of glass particles into the cement led to a cement withincreased creep resistance under bending, a trend attribut-able to the formation of an apatitic layer46; and (3) in freeswelling, its creep rate is higher than that of commerciallyavailable cements.45

Monomer-to-polymer ratio (MPR). In the case of twocements used in VP (Osteopal V and Vertebroplastic), therewas no significant difference in the creep deformation ofspecimens, as obtained in quasi-static four-point bend testsconducted 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/Constituentsa,b Manufacturer/Supplier

Acrylic Bone CementsCMWTM1 Powder (40.00 g): 35.54 g PMMA, 3.64 g

BaSO4, 0.82 g BPODePuy CMW Blackpool, UK

Liquid (18.37 g): 18.22 g MMA, 0.15 gDMPT, 25 ppm HQ

KyphXVR HV-RTM Powder (20.00 g): 13.60 g MMA-styrene co-polymer; 6.00 g BaSO4, 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

PalacosVR

R Powder (40.00 g): 33.55 g poly(methyl acry-late, MMA), 6.13 g ZrO2, 0.32 g BPO, 1.00mg chlorophyll

Heraeus Kulzer GmbH, Hanau,Germany

Liquid (18.78 g): 18.40 g MMA, 0.38 gDMPT, 0.40 mg chlorophyll

Surgical SimplexVR

P Powder (40.00 g): 29.40 g poly(MMA, sty-rene), 6.00 g PMMA, 4.00 g BaSO4, 0.60 gBPO

Liquid (18.79 g): 18.31 g MMA, 0.48 gDMPT, 80 ppm HQ

Calcium phosphate-basedcements

BiopexVR

a-TCP, TTCP, DCPD Mitsubishi Materials Corp., Tokyo,Japan

chronOS InjectVR

Powder: 42 wt.% b-TCP, 21 wt.% MCPM, 31wt.% b-TCP granules, 5 wt.% Mg hydro-gen phosphate trihydrate, < 1 wt.% so-dium hydrogen pyrophosphate Mg(SO4)2

Oberdorf, Switzerland

Liquid: 0.5% solution of sodium hyaluroneNorianVR Skeletal Repair

Systema-TCP, CaCO3, MCPM Synthes, Inc.,West Chester, PA, USA

Calcium sulfate-based cementsAlloMatrixV

R

CaSO4.0.5H20; demineralized bone matrix Wright Medical Technology,Arlington, TN, USA

MIIGVRX3 CaSO4.0.5H20 Wright Medical TechnologyFilamentary composite cementCortossV

R

bis-GMA, bis-EMA, TEGDMA, glassparticles

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

VRcement were taken from products’ brochures.


inconsistent with the relative MPRs for the cements; specifi-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 duringthe preparation of a test specimen. For both Mendec andKyphX cement specimens, over a range 170 kPa � p �3200 kPa, mean creep strain, as determined in dynamiccompression tests on specimens in Ringer’s solution, at37�C, decreased with increase in p, a trend that was attrib-uted to an increase in cement density (and, hence, decreasein porosity of the specimens) accompanying the increasein p.47

Cement mixing method. Under quasi-static compressiveloading, over the stress range of 30–50 MPa, the meancreep strain of unconstrained specimens of Palacos R andZimmer R, kept moist, was significantly lower on specimensfabricated from vacuum-mixed cement compared to hand-mixed cement, which was attributed to a significant reduc-tion in porosity brought about with vacuum mixing.39

Duration of cement mixing. An increase in the timeinterval between the beginning of vacuum mixing of thecement constituents and injection of the curing dough intothe specimen mold (from 90 s (‘‘standard injection’’) to270 s (‘‘delayed injection’’)) significantly increased the creepstrain of unconstrained Palacos R specimens subjected toquasi-static compressive loading while immersed in salineat 37�C.40 Similar trends in strength values were attributedto the formation of laminations within ‘‘delayed injection’’’specimens.60

Length of aging timeUnder quasi-static tension loading (stress ¼ 3 MPa), thecreep rate of specimens of a PMMA bone cement, at anycreep time, decreased with increase in length of aging (7–24 days) in a given test medium (air, water, Ringer’s solu-tion, or Intralipid (a fat solution designed to simulate thefat in the bone cavity)), a trend that was consistent withwork on physical aging.42

For unconstrained Surgical Simplex P specimens sub-jected to quasi-static four-point bending, creep deflectiondecreased significantly with increase in the aging time ofthe specimens, ta (defined as the time interval betweenimmersion of the specimen in saline at 37�C (1 h � ta �28 days) and testing in saline at 37�C).43 This trend wasattributed to the reduction of the plasticizing influence ofthe liquid monomer with increase in ta as the monomercontent was reduced by continued polymerization.43

For unconstrained Palacos RþG and SmartSet GHV speci-mens subjected to quasi-static three-point bending, creepcompliance decreased significantly with increase in agingtime (defined as the time interval between immersion ofthe specimen in water, at 37�C, and testing in Ringer’s solu-tion, at 37�C) (over the range 45 min to 2.5 years), a trendthat was related to the mobility of the polymer chains.51

For both SmartSet GHV and Palacos RþG specimens, theinfluence of length of the time the specimens were aged (indemineralized water, at 37�C) prior to the creep test (te), onthe creep of the specimens was the same; specifically, linearincrease of log to with log te and linear increase of g0

with log te.51

While the experimental evidence shows unanimity thatincrease in aging time led to decrease in a given creepparameter,42,43,51 various explanations have been putforward for this trend.

Test medium composition. Under quasi-static loading, themean creep strain rate of Sulfix 6 and Zimmer LVC speci-mens was significantly lower when tested in water than inair, which points to the possibility that the creep resistanceof the bone cement in a cemented TJR may not be compro-mised.61 Under quasi-static compressive loading, the meancreep 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 whenthe testing medium was saline, a trend that was attributedto the plasticizing effect of the fat.43

Under quasi-static tension loading, the creep rate ofspecimens of a poly(ethyl methacrylate) (PEMA) bonecement (aged and tested in the same solution, at 24�C), atany test temperature, was significantly influenced by thetest medium, with the rate being similar in distilled waterand Ringer’s solution, each rate of which was higher than inIntralipid, which, in turn, was higher than in air. Thesetrends were explained by the plasticization by each of thewater-based media (water and Ringer’s solution) and theincrease of leaching of the monomer from specimens testedin Intralipid.42

Test medium temperature. Under quasi-static tension load-ing (stress ¼ 3 MPa), the creep rate of specimens of aPEMA bone cement, tested in a given medium (air, water,Ringer’s solution, saline, or Intralipid) increased withincrease in the medium temperature (T); for example, in air,in the range 24�C � T � 50�C, there was a very smallincrease in the rate in going from 24�C to 30�C and from30�C to 40�C, and a very large increase between 40�C and50�C.42 In dynamic loading tests on restrained hand-mixedCMW 1 and Palacos R specimens, creep strain when thespecimens were tested at ‘‘body temperature’’ was substan-tially higher than when tested at ‘‘room temperature,’’ afterthe initial creep stage (i.e., at number of test cycles >

1,271,400 cycles).54 These trends54 suggest that an increasein test medium temperature increases the effects of plastici-zation and are consistent with creep in a given test mediumbeing considered a thermally activated process.62

Constraint of test specimen. Under dynamic creep condi-tions, the creep strain of fully restrained hand-mixedCMW2000 specimens, in room-temperature air, was signifi-cantly lower than when the specimens were semi-restrained.53 This trend is consistent with creep beingdescribed as a consequence of stretching and realignment of

REVIEW ARTICLE


TABLE II. Empirical Relationships for Creep Strain of Commercially Available PMMA Bone Cement Specimens

Cement brand Test Conditions Empirical Relationshipa,b Reference

Cemex Dynamic compression log e ¼ 0.3386 log N – 4.449 Verdonschot and Huiskes41

Isoplastic Hand-mixedUnconstrainedSaline, at 38.5�C

Cemex RX Dynamic compression log e ¼ 0.3743 log N – 4.366 Verdonschot and Huiskes41

Hand-mixedUnconstrainedSaline, at 38.5 �C

Cemex Dynamic compression log e ¼ 0.3101 log N – 4.148 Verdonschot and Huiskes41

System Mixed within a syringeUnconstrainedSaline, at 38.5�C

CMW1 Dynamic tension log e ¼ [�0.13 log r þ 0.42] log N Jeffers et al.48

Vacuum-mixed þ [3.12 log r – 2.61]UnconstrainedDistilled water, at 37�C

CMW1 Dynamic compression e (%) ¼ 0.099 ln N – 1.178 Liu et al.54

Hand mixedFully constrainedTest medium temperature:‘‘Room temperature’’

CMW1 Dynamic compression e (%) ¼ 0.176 ln N – 2.151 Liu et al.54

Hand mixedFully constrainedTest medium temperature:‘‘Body temperature’’

CMW2000 Dynamic compression e (%) ¼ 0.088 ln N – 1.029; Liu et al.53

Hand-mixed r2 ¼ 0.925Fully constrained

CMW2000 Dynamic compression e (%) ¼ 0.088 ln N – 0.7989; Liu et al.53

Hand-mixed r2 ¼ 0.898Semiconstrained

Palacos R-40 Dynamic compression e (%) ¼ 0.069 ln N – 0.622 Liu et al.54

Hand-mixedFully constrainedTest medium temperature:‘‘Room temperature’’

Palacos R-40 Dynamic compression e (%) ¼ 0.2002 ln N – 2.371 Liu et al.54

Hand mixedFully constrainedTest medium temperature:‘‘Body temperature’’

SmartSet Dynamic compression e (%) ¼ (0.448N)/(1,063,111 þ N); Liu et al.55

GHV Hand mixed r2 ¼ 0.96SemiconstrainedTest medium temperature:‘‘Room temperature’’

SmartSet Dynamic compression e (%) ¼ (1.787N)/(180,332 þ N); Liu et al.55

GHV Hand mixed r2 ¼ 0.99SemiconstrainedTest medium temperature:‘‘Body temperature’’

SmartSet Dynamic compression e (%) ¼ (0.410N)/(1,184,562 þ N); Liu et al.55

GHV Hand mixed r2 ¼ 0.97Fully constrainedTest medium temperature:‘‘Room temperature’’

Surgical Dynamic compression ec ¼ 1.22 � 10�5 N0.31100.03r Verdonschot and Huiskes39

Simplex P Hand-mixedUnconstrainedSaline, at 38.5�C

Surgical Dynamic compression log e ¼ 0.3488 log N – 4.426 Verdonschot and Huiskes41

Simplex P Hand-mixedUnconstrainedSaline, at 38.5�C

Zimmer Quasi-static compression e ¼ 1.76 � 10�9 r 1.858 t0.283 Chwirut36

Regular Hand-mixed e ¼ 3.02 � 10�4 e(9.37 � 10-4r)t0.283

UnconstrainedSaline, 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 r2 is the coefficient of multiple determination of the fitted equation.

molecule chains in the cement in that, in a fully restrainedspecimen, 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 theelastic strain of an unconstrained cement specimen(¼applied stress on specimen/elastic modulus of cement),at a given stress level, may be computed using a best-fitrelationship (derived from experimental results; for exam-ples, see Table II). This time (which is inversely pro-portional to the creep rate) was significantly shorter undercyclical tensile load than under cyclical compressive load, atstresses > 5 MPa.39 Furthermore, these times, as obtainedfrom dynamic compression tests, were significantly higherthan under quasi-static compression, at stresses > 5MPa.36,39

Magnitude of applied stressUnder quasi-static tension loading, the creep rate of speci-mens of a PEMA bone cement, in a given test medium (air,distilled water, Ringer’s solution, or Intralipid), increasedmarkedly with increases in the magnitude of the appliedstress, which reflects the fact that, with increase in stress ina given test medium, there is increase in the plasticizationeffect of the medium.42

Empirical relationships and modeling. A number of em-pirical relationships have been derived from experimentalresults (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), Struik’s 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 first is to compute thehorizontal shift factor, aT, using, in most cases, the Struikequation for compliance, D, at a given test temperature andtest time, t, along with aT. Thus, the governing equation forD(t) is63

DðtÞ ¼ Do exp ðt:aT=sÞm; (1)

where Do is the initial compliance and s and m are con-stants. For the PEMA cement, at T ¼ 37�C, the best-fit val-ues of the constants were: Do ¼ 3.33 GPa�1, s ¼ 7305 s,and m ¼ 0.276.50 The second step is to determine the qual-ity of the fit of the Williams-Landel-Ferry (WLF) equation tothe experimentally obtained results for the variation of aTwith T. This equation is given as64

logðaTÞ ¼ C1ðT � TsÞC2 þ ðT � TsÞ (2)

where T is the temperature of the test medium, Ts is a ref-erence temperature (usually, taken to be the glass transitiontemperature of the cement) and C1 and C2 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 C1 ¼ 17.4 and C2 ¼ 75 K, the fit to the experimentalcreep compliance (and, hence, rate) results was excellent(Figure 2).

SETM is used to account for the influence of aging ofthe specimen. The essence of this method is that it may beused to determine the effective time of a creep test (k),which is defined as the time required to achieve the samecreep strain if aging had been ongoing. The expression usedto compute k is as follows:

k ¼ tetc � ate

þ 1

� �1=a

� 1

" #(3)

where te is the aging time, tc is the actual creep time, anda ¼ (1-l), with l (the aging rate) being the slope of theplot of log aT versus log te. 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 ofSETM compared with when TTSP was used is evident50

(Figure 3).ITFM involves three steps. The first is to generate the

momentary creep curve, with physical aging not being con-sidered important. This is done by obtaining the fit betweenthe experimental creep data, on one hand, and either theStruick equation [Eq. (4)] or the Williams-Watts equation65

[Eq. (5)], on the other.

DðtÞ ¼ D0 expt

s

� �m

(4)

DðtÞ ¼ Do þ DDa½1� exp ð�t=sÞm� (5)

FIGURE 1. Variation of shift factor, aT, with test temperature, T, and

the fit between the Williams-Landel-Ferry (WLF) equation and the ex-

perimental results, for a poly (ethyl methacrylate) bone cement. (With

kind permission from Springer ScienceþBusiness Media; Journal of

Materials Science: Materials in Medicine, Prediction of the long-term

creep behaviour of hydroxyapatite-filled polyethylmethacrylate bone

cements, volume 18, 2007, page 1854, J. C. Arnold and N. P. Venditti,

Figure 6).

REVIEW ARTICLE


where D, t, Do, s, and m have the same meanings as givenbefore and DDa is a material constant.

The second step is to use results from a long-term creeptest, where aging is important, to obtain values of C and bas used in the integrated time function. This is accom-plished thus: (1) plot the equation

FðDðtÞÞ ¼ t

sðtÞ (6)

with the F(D(t)) applicable to the Struik equation [seeEq. (7)] or to the Williams-Watts equation [see Eq. (8)].

DðtÞ ¼ D0 expZt

0

duðuÞ

24

35m

(7)

DðtÞ ¼ D0 þ DDa 1� exp �Zt

0

du

ðuÞ

0@

1A

m24

35 (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 thefollowing equation

Z t

0

dusðuÞ where s2ðtÞ ¼ s2 þ C2t2b (9)

The third step is to use the values of the constantsobtained (Do, s, m, C, and b, if Eq (7) is used or Do, s, m, C,b, and DDa if Eq (8) is used) to construct predictive curvesfrom which the long-term creep data may be read. For aPEMA cement, the best-fit values of the material constantsfound were found to be: Do ¼ 2.558, s ¼ 2.097 s, m ¼0.245, C ¼ 0.240, and b ¼ 0.817 (for fit between Eq. (7)and the experimental data) and Do ¼ 3.900, s ¼ 8.00 � 107

s, m ¼ 0.601, C ¼ 2820, b ¼ 0.674, and DDa ¼ 400 GPa�1,(for fit between Eq. (8) and the experimental data).50 Acomparison of the creep compliance versus creep timeresults, for one set of experimental conditions, to the predic-tions using the two variants of the ITFM [i.e., via use ofEq (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 Struik’s

effective time method. (Experimental data obtained at 1 MPa; Ringer’s

solution, at 37�C; and 1 day of aging in Ringer’s solution, at 37�C.)(With kind permission from Springer ScienceþBusiness Media; Jour-

nal of Materials Science: Materials in Medicine, Prediction of the

long-term creep behaviour of hydroxyapatite-filled 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-fit

values for the parameters in the Williams-Landel-Ferry equation: C1 ¼17.4 and C2 ¼ 75 K. (With kind permission from Springer Scienceþ-

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; Ringer’s solution, at 37�C; and1 day of aging in Ringer’s solution, at 37�C.) (With kind permission

from Springer ScienceþBusiness Media; Journal of Materials Science:

Materials in Medicine, Prediction of the long-term creep behaviour of

hydroxyapatite-filled polyethylmethacrylate bone cements, volume 18,

2007, page 1857, J. C. Arnold and N. P. Venditti, Figure 12).


A phenomenological description of the creep compliance(J(t)) of Palacos RþG and SmartSet GHV specimens,obtained in three-point bending (range of specimen agingtime in demineralized water, at 37�C: 45 min to 2.5 years;test medium: Ringer’s 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

JðtÞ ¼ J0 � exp tt0

� �m� �(10)

where Jo, to, and m are the parameters.A physical description of the creep deformation of the

aforementioned Palacos RþG and SmartSet GHV specimenswas presented in terms of the modified Burgers’ model,51

which is given by

eðtÞ ¼ r � 1

E0þ 1

Er� ð1� e�t=sr Þ þ t

gþ 1

Ec� ð1� e�t=scÞ

� �(11)

where Eo is the modulus of elasticity of the cement; 1/Erand sr are the weight and time constant of the viscoelasticrelaxation, respectively; g is the viscosity of the cement;and 1/Ec and sc are the weight and time constant of the pri-mary creep phase, respectively.

Summary. Two observations are in order here. First, inspite of the existence of results from a multitude of studies,the influence of various intrinsic and extrinsic factors onthe creep performance of commercially available PMMAbone cement brands is unclear. This is because the majorityof these studies were not designed to delineate theseaspects. As a result, many of the studies are limited by thepresence of confounding variable(s), the most common ofwhich was the use of different commercially availablebrands. This situation makes it difficult to, for example,assess the impact of a combination of extrinsic factors thatare clinically relevant (for example, cement mixing method,nature of applied stress, and magnitude of stress) on thecreep performance of a given cement brand. Second, thereis limited information on the appropriate model(s) for thecreep behavior of PMMA bone cements. This hampers thedevelopment of rational method(s) of synthesizing a cementbrand from the perspective of creep deformation.

Stress relaxationCement composition and cement brand. For a ‘‘surgicalgrade’’ cement, at a constant compressive strain of 1%, at agiven value of time during the test, the extent of stressrelaxation increased when the cement was reinforced byincorporating 2 wt/wt % chopped carbon fiber into thecement powder.35

The rate of stress relaxation was significantly higher inPalacos R (stress relaxed to practically zero after 6 weeks)compared with both CMW1 and Simplex P (in both, stressrelaxed to 100 kPa after one year).66

During unconstrained stress relaxation tests, conductedunder quasi-static four-point bending, the relaxation of the

load in Surgical Simplex P specimens, with time, whentested in saline solution at 37�C, was not significantly differ-ent from that for PalacosV

R

R specimens tested in the samemedium.44 The loads for both of these sets of specimenswere, however, significantly different than those obtainedwhen specimens fabricated from the family of CMW wereused.43

The trend in the above results for Surgical Simplex Pand CMW143 were different from that determined fromthree-point bend tests on CMW1-G and Surgical. Simplex Pspecimens, at initial strain of 0.3% or 0.6%, or 0.9%.67 Inthe latter case, the reduced stress functions for these twocements were the same.67 For a given combination of con-stant strain and time, the stress in specimens of eitherCMW1-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 insaline solution at 37�C, increased significantly with increasein conditioning time of specimens in the solution, tm (1 h �tm � 10 weeks).43 This same trend was seen when thetests were carried out, in air at ‘‘room temperature’’ undertension (1 h � tm � 7 days)43 and in another series of four-point bending tests (conducted in water, at 37�C.)68

The trend in these results43,68 was attributed to reductionof the plasticizing effect of the monomer with increasein tm.

43

Empirical relationships and modeling. The experimentalevidence (Table III) indicates that, for a given cement, therelaxation of compressive stress with time in the specimenmay 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 at37�C, were described by the Maxwell double-exponentialmodel (Figure 5); thus, the stress (r)-versus-t relationshipis of the form

r ¼ aet=b þ ve�t=d þ c; (12)

where a, b, v, d, c are constants, each of which is related toa material property; for example, b ¼ g1/E1 and d ¼ g2/E2.For specimens aged, in air, at 37�C, for 70 days, the best-fitvalues 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 inwater at 37�C (together with those from damping tests—these are discussed in the next section of this review), theconstitutive equation that links the drop of elastic modulus,E, with time, t, was found to be67

EðtÞ ¼ E1 þ DEðtÞ ¼ E1 þ C1 expð�t=s1ÞþZ 1

0KðsÞ expð�t=sÞds (13)

REVIEW ARTICLE


with K(s) ¼ C2/s þ C3/sn and E1, C1, C2, C3, s, and n are

constants. That is, this drop is describable using one mainrelaxation time (s1) superimposed on a continuous spec-trum of relaxation times. For example, for Surgical SimplexP specimens, the best-fit values of E1, C1, C2, C3, s, and nwere found to be 1000 MPa, 1300 MPa, 130 MPa, 15, 9 �104 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 acement specimen on the basis of results obtained in theshort-term.

Summary. The literature is very limited in a number ofrespects, such as studies on only a few commercially avail-able cement specimens, investigations of only a few influ-encing factors, and a few contributions in the area ofmodeling.

DampingBackground. The ability of a viscoelastic material, such asan ABC, to dissipate strain energy as heat can be deter-mined using a dynamic test. Such a testing mode is relevantto ABC being used in a TJR, in which, during activities ofdaily 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 complexparameter; for example, the complex elastic modulus (E) is

E ¼ E0 þ iE00 (14)

where E0 is the storage modulus and characterizes the mate-rial’s elasticity, and E’’ is the loss modulus and characterizesits internal damping capacity.

Thus,

Loss=damping factor; tan d ¼ E00=E0 (15)

(Note that Eqs. (14) and (15) may also be written in termsof the shear modulus, G.)

Test mode. With one exception, dynamic mechanical ther-mal analysis (DMTA) (sometimes referred to as dynamicmechanical analysis, DMA), operated in three-point bendingmode, has been used to determine E0, E00, and tan d, as afunction of the cured cement specimen’s temperature, T0 (ata fixed test frequency, f).69–71 In a DMTA test, typical speci-men size is 25.0–40.0 mm � 10.0 mm � 1.0–1.5 mm, andtypical test conditions are: displacement, 64 lm; static force,60 mN; dynamic force, 40 mN; rate of heating of specimen,2–4�C min�1; range of T0: 20–200�C; and range of f ¼ 1–30 Hz.69–71 The exception is a study in which the DMTAtests were performed on cured cement specimens, in a dis-placement control mode; that is, using a frequency sweep(0.01–100 Hz) and a temperature sweep (17–57�C).67

Damping properties may also be obtained using a plate-plate configured rheometer (typical radius of plates and gapbetween them ¼ 20–25 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 Relationshipa,b Unit for t Reference

Braxell Hand-mixed r ¼ 4.18 e�0.0054t; s De Santis et al.67

Stored in distilled water, at 37�C, r2 ¼ 0.643for 21 dTested in waterThree-point bend loading

Palacos R Hand-mixed r ¼ 20.49 e�0.020t; h Lee et al.43

Stored in saline, at 37�C, for 7 d r2 ¼ 0.766Tested in saline, at 37�CFour-point bend loading

Simplex P Hand-mixed r ¼ 19.14 e�0.0104t; min Eden et al.68

Stored in air, at 37�, for 6 h r2 ¼ 0.889Tested in water, at 37�CFour-point bend loading

‘‘Surgical grade’’ r ¼ 18.91 e�0.286t h Pal and Saha35

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.


(typically, strain amplitude and frequency ¼ 1% and 1–5 Hz, respectively), with the curing cement being tested at afixed temperature.72–75

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 fixed test fre-quency [Figure 6(a)] and/or (2) the variation of the storagemodulus, the loss modulus, and/or tan d with test time (t)at a fixed combination of T0 and f [Figure 6(b)].

Influence of cement composition. In the case of a PMMAbone cement, in which the radiopacifier was provided byBaSO4 particles (10% p/p) in the cement powder, when drycured specimens were used, the storage modulus, at a givenT0, was practically the same as when radiopacity was pro-vided by incorporating an iodine-containing monomer, 4-iodophenol methacrylate (IPMA) (5–20% v/v), in the liquidphase.70 The same trend was found for the tan d results.70

In the case of a PMMA bone cement in which the radio-pacifier was provided by BaSO4 particles (10%) in thecement powder, when dry cured specimens were used,the storage modulus, at a given T0 (f fixed), was practicallythe same as when radiopacity was provided by any one ofthree other radiopacifiers (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 trendwas found for the tan d results.71 Up to tm � �16 min, thepattern of increase of G0 with increase in time from com-mencement of mixing of the cement, tm (at a fixed combina-tion of T0 and f) was practically the same when the radiopa-cifier was 10 wt % BaSO4 particles in the powder as whenany one of three other radiopacifiers incorporated in thecement powder (10 wt % strontium hydroxyapatite (SrHA),10 wt % SrHA treated with MMA (SrHA-m), and 20 wt %SrHA-m).75 For tm > �16 min, there were similarities anddifferences seen in the plots for the four cements: for the10 wt % BaSO4-containing cement, there was a sharp risein G0 (corresponding to an increase in polymerization); forthe 20 wt % SrHA-m-containing cement, there was a slowrise in G0 for up to tm �10 min, followed by a sharp risethereafter; and for each of the other two cements, G0

increased at the same rate as during tm � �16 min.75 All ofthe aforementioned patterns were also seen in the G00

results.75

Influence of cement brand. In a displacement controlmode experiment, (1) up to f ¼ 10 Hz, the mean value oftan d for the cured Braxell specimens was about the sameas for the cured CMW1 and Surgical Simplex P specimens;(2) in the range 10 Hz < f < 100 Hz, tan d for the curedBraxell specimens was marginally higher than for the othertwo cured cement specimens; and (3) the increase in tan d,with increase in f, was slightly greater for the cured Braxellspecimens compared with those of the other cements.67

These results suggest that the main factor that influencesthe damping factor in a PMMA bone cement is the constitu-ent of the main polymer chain; in other words, since PMMAis the main polymer in Braxell, CMW1, and Surgical SimplexP, their tan d-f profile was about the same.67

Influence of size of PMMA beads. For experimental PMMAbone cements designed for use in VP and BKP, at a givenvalue of tm (for a fixed combination of T0 and f), a decreasein the ratio of large PMMA beads (mean diameter ¼ 118lm) to small ones (mean diameter ¼ 70 lm) (we designatethis ratio R, in wt /wt %) in the powder led to an increasein both G0 and G00.72 This trend was attributed to the disso-lution of the small beads (and, hence, the beginning ofincreasing polymerization rate) appearing earlier as Rincreases.72

Influence of state of hydration of test specimens. In thecase of a PMMA bone cement in which the radiopacifier wasprovided either by adding BaSO4 particles (10% p/p) to thecement powder or by incorporating IPMA (5–20% v/v) inthe liquid phase, for both dry and wet cured specimens, at agiven T0 (f fixed), the pattern of change of storage moduluswith test temperature was unaffected by the state of hydra-tion of the test specimen.70 For the tan d results, (1) foreach cement, there was a broadening of the plots when wetspecimens were used compared to when dry ones wereused, which was attributed to a plasticizing process70; 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.

REVIEW ARTICLE


(2) there was a slight reduction of the temperature at whichthe peak occurred, dropping from a mean of �127�C whendry cured specimens were used to a mean of �115�C whenwet cured ones were used in the case of the BaSO4-contain-ing cement and from a mean of �129�C to a mean of�116�C when dry and wet cured IPMA-containing cementspecimens were used, respectively.70 These same trendswere obtained in the case of a PMMA bone cement in whichthe radiopacity was provided by BS, BSPEO, or BSDM.71

Influence of test frequency, f. In a displacement controlmode experiment, for a given cement (Braxell, CMW1, orSurgical Simplex P), with tests conducted on cured speci-mens immersed in water, after conditioning them in distilledwater, at 37�C, for 21 days, each of the dynamic properties(storage modulus, loss modulus, and loss factor) increasedwith increase in f.67 It has been suggested that this phenom-enon may provide an explanation for the fact that, althoughPMMA bone cement is brittle, under quasi-static loading,it provides excellent resistance to dynamic loading (thatis, it acts as a shock absorber), as is experienced inthe cement in a TJR during many activities of daily living,notably gait.76

Influence of test temperature (T). In a displacement con-trol mode experiment on Surgical Simplex P specimens, at agiven value of f (0.1 Hz �1 f � 10.0 Hz), there was a trendof 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 oncured Braxell, CMW1, and Surgical Simplex P specimens,conducted in water (together with those from stress relaxa-tion tests—stress 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 (whichwould provide an excellent fit to the stress relaxationresults) and a continuous spectrum (which will provide anexcellent fit to the DMTA results) [see Eq. (13)].67 Thus, thefollowing expressions were found to describe the increaseof E0 and E00 with increase in f (x ¼ 2pf)77:

E0ðxÞ ¼ E1 þ xZ 1

0DEðsÞ sinðxsÞds (16)

E00ðxÞ ¼ xZ 1

0DEðsÞ cosðxsÞds (17)

where E1 is a material constant and E is the viscoelasticmodulus.

Summary. There is a modest number of studies on influ-encing factors, from which it appears that a significantintrinsic parameter is the powder particle size distribu-tion while test frequency and test temperature are signif-icant extrinsic factors. Furthermore, there is a plasticizingeffect on tan d and there is a dearth of work onmodeling.

Rheological propertiesVariation of viscosity of cement with time. The primaryrheological parameter is the variation of the viscosity of thepolymerizing cement with time. Four approaches have beentaken for such determination.

In the first, a rotational or capillary extrusion rheo-meter/viscometer was used.78–81 With this set-up, the vari-ation of the pressure gradient (P) with tm is obtained,which leads to the variation of the apparent or false viscos-ity of the cement (l) through use of the Hagen-Poiseuilleequation:

l ¼ pPR4

8LQ(18)

where R is the radius of the capillary/die, L is the length ofthe capillary, and Q is the volumetric flow rate of thecement dough (or the rate at which the cement dough isinjected into the capillary). A typical l-time plot is given inFigure 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.


In the second approach, the viscosity tests were per-formed using a commercially available device that basicallyinvolved 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 ¼ 28mm and 610 mm2, respectively), at a defined speed (typi-cally, 0.03 mm/s), into the dough as it polymerizes. In thepresent review, we shall designate the plot of the resultsobtained using this device as the ‘‘force viscosity’’-versus-tmplot.82,83

In the third approach, the cement dough was placed intothe cup of a rheometer that has a cup-and-plate configura-tion (or on the lower plate of a rheometer that has a plate-plate configuration), bringing the plate or top plate to touchthe dough, and then performing the test in a dynamicoscillation mode (i.e., the plate or top plate is subjected to adisplacement (typically, 6 10 lm) at a fixed frequency (typ-ically, 1–5 Hz).72–75,84–86) The rheometer is a force-reso-nance analyzer which means that the peak compressiveforce transferred from the curing cement (F) to the plate istracked by a force transducer, as a function of tm. The F–tm results are exported to a computer containing a soft-ware that converts these results to complex viscosity (g*)-versus-tm results.84–86 Typical g*-tm results are given inFigure 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 drivenby a computer-controlled electromagnetic actuator.87 Theactuator uses a model to obtain both the displacement andthe torque without the use of sensors, from which thestorage modulus (G0) and the loss modulus (G00) of the curingare obtained. A software package in the computer convertsthese moduli to g* using the following relationships:

g0 ¼ G00=x; g00 ¼ G0=x; g� ¼ g0 � ig00 (19)

The issue of comparability in the viscosity-tm resultsbased on the viscosity measurement method used hasreceived very limited attention, with one study being onCMW3.84 For this cement, at a given value of tm, it wasfound that g* is markedly higher than l, a finding that is inconsonance with the Cox-Merz rules.88 A caveat should beattached to this result because, g* was experimentallydetermined in one study84 but the corresponding l resultwas taken from another study/report.17

Categorization of cement brands. Results of the variationof l with tm has been used to categorize commercially avail-able cements into ‘‘low-viscosity’’ cements (for example,Zimmer LVC; l ¼ 1 kPa s at tm ¼ 5 min); ‘‘medium-viscos-ity’’ cements (for example, Surgical Simplex P; l ¼ 5 kPa sat tm ¼ 5 min) and ‘‘high-viscosity’’ cements (for example,Palacos R; l ¼ 14 kPa s at tm ¼ 5 min).89

Explanation of viscosity-time profile. When g* is deter-mined, it is seen that, with increase in tm, there is an initialsteady rise, followed by a final rapid rise. The former stage

is due to swelling and dissolution of the polymer beads inthe liquid monomer as the powder is wetted by the mono-mer, while the latter stage is due to the polymerizationreaction.84,90

Influencing factors. The importance of the composition ofthe powder beads in a PMMA bone cement is exemplifiedby the clear differences in the ‘‘force viscosity-versus-tresults for two commercially available PMMA bone cements;specifically, a tobramycin-loaded cement (Simplex withTobramycin) showed a lower initial value of median ‘‘forceviscosity’’ than a gentamicin-loaded cement (Palacos RþG).In Simplex with Tobramycin, the beads are of MMA-styrenecopolymer and, thus, are more hydrophobic (take longer todissolve in the liquid monomer) than the MMA-MA beads inPalacos RþG.83

On the basis of the ‘‘force viscosity’’-versus-time resultsobtained from three variants of a commercially availablegentamicin-loaded PMMA bone cement (Refobacin PalacosR, Palacos RþG, and Refobacin Bone Cement), it was sug-gested that, for a gentamicin-loaded cement, the median‘‘force viscosity,’’ at a given tm, may be influenced by varia-tion in the polymer/copolymer particle size ratio.82 Appa-rent contradictions in the ‘‘force viscosity’’-versus-tm resultsfor Palacos RþG and Refobacin Bone Cement from the sameresearch group82,83 point to the need for further study ofthe issue of the significance of variation in composition of agiven gentamicin-loaded PMMA bone cement vis a vis curingcement 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*-tmprofiles are of the same form. Thus, differences were notedin this profile for Cemex Isoplastic, CMW1, and Palacos R,each of which is a ‘‘high-viscosity’’ brand.73 Specifically, dur-ing the early stages of curing, Cemex Isoplastic was themost viscous, and Palacos R the least viscous, with CMW1becoming the most viscous in the latter stages of curing.73

For an experimental cement, whose radiopacity was pro-vided by ZrO2 (5–30%), for a given amount of ZrO2, l wassignificantly higher when cross-linked PMMA nanosphereswere added to the powder than when cross-linked PMMAmacrospheres were added. This was attributed to (1) thehigher surface area of the nanospheres, which translates tohigh diffusion of the liquid monomer81; and (2) increase inthe volume fraction of particles in the powder mixture.91

Each of three experimental cements designed for use inVP and BKP (radiopacifier: 10%BaS04; radiopacifier: 10%BaSO4 þ 5% ciprofloxacin (CFX); and radiopacifier: 10%BaS04 þ 3% CFX þ 3% vancomycin) displayed g*-tm char-acteristics, in the initial stage, that are very similar to thosefor a commercially available PMMA bone cement (OsteopalG) at tm < �6 min.74 Because of delayed setting, however,g* remains constant and low for much longer (up to tm >

�11 min) before a final sharp rise in the case of the experi-mental cements.74

The influence of radiopacifier on the g*-t profile of anABC depends on the section of the curve being considered.

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Thus, for an experimental cement, for tm � �15 min, theg*-t curve was practically the same when the radiopacifierwas 10 wt % BaSO4 particles in the powder as when anyone of three other radiopacifiers (10 wt % SrHA, 10 wt %SrHA treated with MMA (SrHA-m), and 20 wt % SrHA-m)was blended into the powder.75 For tm > �15 min, therewere similarities and differences seen in the plots for thefour cements. For the 10 wt % BaSO4-containing cement,there was a very sharp rise in g* (which corresponds to anincrease 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 twocements, g* rose at a moderate rate.75

Reducing the modulus of a PMMA cement for use in VPor BKP, by adding N-methyl-pyrrolidone to the liquid mono-mer (50–60%), led to a significant reduction in the poly-merization rate, as manifest through a significant reductionin g*, at any given tm.

80 This trend is attractive in that itshows an approach that may be taken to widen the windowfor injecting the cement into the cannula during VP or BKP.

The importance of the dispersal of an additive in thecement on the viscosity-time characteristics is illustrated byresults from two variants of an experimental cement, one inwhich a clay (2% sodium montmorillonite (SMMT) or 2%organophilic montmorillonite (OMMT)) was blended withthe powder and the other in which the clay was added tothe liquid monomer. In each variant, there was an increasein g*, at a given tm (relative to case for the plain cement),with this trend being likely due to the clay increasing theshear modulus of the cement.85 More importantly, however,at a given tm, a cement in which OMMT was added to theliquid monomer showed the highest g*, this trend beingattributed to the clay in this cement being well dispersed.85

For Palacos R, a decrease in the temperature at whichthe cement was stored prior to mixing (Tst) led to adecrease in l throughout the polymerization period.79 Alter-natively, for this cement, the time taken to reach a specifiedviscosity increases with increase in Tst.

79 These trends maybe explained in terms of the fact that lowering of Tst leadsto delay of generation of free radicals, which translates todelaying the initiation of the polymerization process.79

The time taken to reach a specified viscosity decreaseswith increase in the temperature of the room in which thecement is mixed (Ta).

90 This observation highlights the needto ensure that, during a cemented TJR procedure, the tem-perature of the operating room does not fluctuate at theearly stages; that is, during the time interval betweencement preparation and hardening of the cement in thebone bed.

The method used to mix the cement is an importantinfluencing factor. Thus, for each of three commerciallyavailable PMMA bone cements (Antibiotic Simplex, DP-Pour,and Vertebroplastic), mean l, at a given time (tm), wasmarkedly higher when the cement was hand/manuallymixed compared to when it was mixed using an oscillatingmachine (shaking stroke amplitude and frequency ¼ 20 mmand 10 Hz, respectively).78 This trend was attributed to thepseudoplastic behavior of PMMA bone cements; that is, the

thinning of the cement when subjected to a large shear strainas is experienced during oscillatory mixing. Furthermore, at agiven t, the coefficient of variation (standard deviation/mean) of the l results, which is a measure of their reprodu-cibility, was markedly lower when oscillatory mixing wasused compared with when hand mixing was used.78 This wasattributed to the fact that the oscillatory mixing conditionswere controlled (fixed shaker stroke amplitude and fre-quency) whereas the hand mixing conditions were not.78

For a given cement, for a given tm, l decreases withincrease in shear rate, c, in a manner describable by the fol-lowing power equation92

l ¼ at

ts

� �þ b

� �� c

cs

� ��cðt=tsÞþd

(20)

where ts is a characteristic time, cs is a characteristic shearrate, and a, b, c, and d are constants, all of whose values aredetermined from the fit between the experimental data andEq. (20). For example, for Surgical Simplex P, for 3.0 min �tm � 5.0 min and 0.4 s�1 � c � 100 s�1, the best-fit valuesof the constants in Eq. (20) were found to be: ts ¼ 1.0 min,cs ¼ 1.0 s�1, a ¼ 590.0 Pa s, b ¼ �1048.8 Pa s, c ¼�0.026, and d ¼ �0.290.92,93 This observation of l decreas-ing with increasing c, which shows that curing cement is apseudoplastic material, has clinical relevance in that it couldbe used by orthopaedic surgeons in making a decision as towhether to insert the cement dough into the prepared bonebed rapidly or slowing. Any such decision, however, shouldalso take cognizance of the influence of delivery speed oncement interdigitation; specifically, interdigitation is facili-tated by slow delivery of the cement dough. This sametrend, namely, decrease of viscosity with increase in shearrate, at given value of t, was seen when g* results wereused.86

Summary. There is a sizeable literature on the influence ofan assortment of intrinsic factors, such as cement composi-tion, and extrinsic factors, such as cement mixing method,on the viscosity-time profile of a PMMA bone cement. Theensuing databank of results allows the identification of fac-tors to be used in order to obtain a desired profile of vis-cosity-time following commencement of cement mixture.

Relationship between handling, viscosity,and damping parametersThree handling parameters that are related to the viscosity-versus-tm profile are: (1) the time of onset of cure(tons),

72,74 (2) the critical cure rate (CCR),84 and (3) thecure time (tcur).

73 Both tons and CCR were estimated fromthe g*-tm results. tons was defined as the time at whichthere was a significant increase in g*84 or as the time atwhich the intersection of the linear fits of the initial andfinal zones in an g*-tm plot occurs.72 From a phenomeno-logical perspective, tons may be regarded as the time atwhich the process that accounts for the viscosity of thecement changes from dissolution of the PMMA beads in theliquid monomer to polymerization.72 CCR was defined as


the value of the time derivative of the best-fit equation tothe initial stage of the g*-tm results with tm being put equalto tons in that derivative.84 For example, for CMW3, theaforementioned best-fit equation was found to be84:

g� ¼ 1713:655tm1:691 ðfor 0 � tm � 8:5minÞ r ¼ 0:998

(21)

Since tons was found to be 12.03 min,84 CCR ¼ 1.62 �104 Pa s min�1.

For PMMA bone cements for use in TJRs, both tons andCCR increased significantly with increase in both the rela-tive amount of small-sized PMMA beads (mean diameter, d,between 0 and 40 lm) in the cement’s powder (we desig-nate this ratio, a) and the relative amount of large-sizedPMMA beads (d > 75 lm) in the cement’s powder (we des-ignate this ratio, b).84 This was explained as follows: duringpolymerization, the small-sized PMMA beads are completelydissolved in the liquid monomer, while the dissolution ofthe large-sized PMMA beads takes a longer time; thus, higha leads to high CCR and high b leads to high tons.

84

Bead size is also important for PMMA bone cements foruse in VP and BKP. For one experimental formulation of sucha cement, an increase in the proportion of small PMMA beads(mean diameter ¼ 70 lm) to large ones (mean diameter ¼118 lm) (we designate this ratio, H, in wt/wt %) led to anincrease in tons.

72 For example, tons was 7 min and �13 minfor H ¼ 0.11 and 9.00, respectively.72 This trend was attrib-uted to the dissolution of the beads (and, hence, the onset ofpolymerization) appearing earlier as H increases72

For experimental cements designed for use in VP andBKP, there is a linear relationship between tons and settingtime (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 tonsvia the testing standard because there is widespread famili-arity with the standard.

From results of the variation of G0, G00, and tan d with tm,tcur was obtained as the time at which these parametersreach a maximum, minimum, and minimum, respectively.73

With this approach, for Cemex Isoplastc, CMW1, and PalacosR, tcur decreased by �50% when the temperature at whichthe measurements were made was increased from 25�C to37�C,73 which reiterated the point that cement curing is athermally activated (Arrhenius) process.62

Strain rate dependence of mechanical propertiesWith increase in the strain rate used in a test (e

:), marked

increases in various mechanical properties of differentcement brands have been reported. Specifically, 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 acommercially available antibiotic-loaded PMMA bonecement (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 wereloaded quasi-statically)95; and (3) for a carbon fiber-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 findings,94–96 which underscore the fact thatPMMA bone cement is a viscoelastic material, highlight theneed to state, in comparisons of results from various litera-ture studies of a specified mechanical property for a givencement, the loading rates used in these studies.

CALCIUM PHOSPHATE CEMENTS

Viscosity-time and damping profilesMethod of determination. For viscosity determination,two types of rheometers have been used. One is a capillaryrheometer, which leads to determination of false or appa-rent viscosity (l).78,97–100 The other is a cone-and-plate sys-tem, in which a predetermined shear rate-versus-time waveis imposed on the CPC slurry, allowing determination ofshear stress-versus-shear strain rate curve and, hence, ifdesired, dynamic viscosity (g*)-versus-tm profile.101–103

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 resultingshear stress and shear strain values to determine G0

and G00.101–103

Characteristic features. At a given combination of condi-tions in a dynamic viscosity test (i.e., for a fixed combinationof applied frequency and strain), G0, G00, and g all increasewith increase in tm, in accordance with the followingpower-law relationship

S ¼ a expðbtmÞ; (22)

where S is a given rheometric parameter (that is, G0, G00, org*), a represents the initial value of the parameter (i.e., avalue that denotes the state of the grains in the CPC slurryprior to commencement of the setting reaction), and b isrelated to the rate of the setting reaction.103 For example,using G0 results for a slurry of a CPC (powder: equimolarTTCP (mean particle diameter: 13.3 lm) and dicalciumphosphate anhydrous (DCPA; mean particle diameter: 0.63lm); liquid: deionized water), the best-fit values of a and bwere found to be 1621 Pa and 6.45 � 10�3 s�1, respec-tively, when the slurry powder-to-liquid ratio (PLR) and testtemperature were 2.00 g mL�1 and 37�C, respectively.103

The existence of a hysteresis loop in the shear stress-versus-shear rate profile 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 anovershoot of the shear stress in the initial stage of the vis-cosity-versus-shear rate profile when shear rate was lessthan 1.5 s�1 (Figure 8), indicating the existence of a yieldstress in the slurry.103 A CPC slurry is a non-Newtonianfluid that displays shear thinning, evidenced by the factsthat (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) G0, G00, and g* all decrease with increase in the shearstrain used in a dynamic viscosity test, for a given test fre-quency (x)103; 3) at x greater than a critical value (forexample, 0.2 rad s�1103), g* decreased with increase in x103

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and (4) at x greater than a critical value (for example, 0.7rad s�1103), both G0, G00 decreased with increase in x.103

Influencing 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 definedto be the various CaP compounds.) Thus, at a given shearrate, the viscosity of an experimental CPC (powder: 50 wt/wt % amorphous calcium phosphate (ACP) þ 50 wt/wt %DCPD; median powder particle diameter: 3.0 lm; liquid:deionized water; PLR ¼ 2.0 g mL�1) decreased significantlywith increase in the amount of strontium carbonate (SrCO3;median diameter; 2.5 lm) added to the cement powder,over the SrCO3 content range of 0–20 wt/wt %.98 For exam-ple, at 1 � 10�2 s�1, viscosity decreased by a factor of 10when 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 % SrCO3 may havepromise for use in VP and BKP.98

The particle size in the powder suspension of a CPCexerts a marked influence on the viscosity of its slurry. Forexample, at a given PLR, the viscosity of a slurry of a b-TCPCPC increased with increase in the time over which thepowder was milled in a planetary mill, tm (3 � tm �30 min), with this trend being a result of the decrease in par-ticle size in the powder suspension with increase in tm.

102

PLR is, arguably, one of the most important influencingfactors on viscoelastic properties of a CPC slurry. At a givenhydration time, G0, G00, and g* of the slurry of each of twoexperimental CPCs (CPC1: powder: 1M TTCP (median dia-meter: 0.39 lm–18.33 lm) þ 1M DCPA (median diameter:8.38 lm–21.70 lm) þ 3.0 wt/wt % hydroxyapatite (HA)

(diameter: 10–20 lm); liquid: deionized water; and CPC2:b-TCP powder þ deionized water, xanthan, or sodium poly-acrylate) all increased significantly with increase in PLR ofthe CPC (1.67 � PLR � 2.50).102 This trend was attributedto decrease in particle-particle interaction with decrease inPLR.102 The significance of PLR is also reflected in its effecton the size of the thixotropy loop (in the shear stress-shearrate plot), with this size decreasing from large (at PLR ¼2.00 or 2.50 g mL�1) to practically zero (at PLR ¼ 1.67 gmL�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 influencedby the viscosity of the aqueous medium used to prepare theslurry and the amount of the medium. For example, inthe case of CPC2, using xanthan or sodium polyacrylate asthe medium led to significant increase or significantdecrease in viscosity, respectively, relative to when deion-ized water was used.102 Furthermore, the viscosityincreased with increase in the content of some additives(xanthan; 0.1% and 0.2 vol %)102 but decreased withincrease in the content of some other additive (sodium poly-acrylate; 0.5 vol % and 1.0 vol %).102 Xanthan promotesflocculation, which, it is suggested, is brought about by theadsorption of one polymer molecule onto more than onesuspended particle, bridging the two particles together, andforming a stable single bloc.104 In contrast, sodium polya-crylate, being a dispersing modifier, causes an increase inthe electrostatic repulsion forces between the particles.105

The details of the influence of cement mixing method onviscosity results depends on the CPC considered. Thus, forone commercially available CPC (Biopex), mean l, at a givent, is, essentially, unchanged when the cement was hand/manually mixed compared to when it was mixed using anoscillating machine (shaking stroke amplitude and fre-quency ¼ 20 mm and 10 Hz, respectively).78 In contrast, foranother commercially available CPC (chronOS Inject), themean l, at a given t, was significantly lower when thecement was mixed using an oscillating machine (shakingstroke amplitude and frequency ¼ 20 mm and 10 Hz,respectively) compared to when it was hand mixed.78 Thelatter trend was attributed to the pseudoplastic behavior ofPMMA bone cements; that is, the thinning of the cementwhen subjected to a large shear strain as is experiencedduring oscillatory mixing. For each of these two cements,however, at a given t, the coefficient of variation of the lresults 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) werecontrollable, whereas the hand mixing conditions werenot.78

G0 of the slurry of an experimental CPC (powder: equi-molar of TTCP (median particle diameter: 13.3 lm) andDCPA (median particle diameter: 0.63 lm) þ 3 wt/wt %HA (particle diameter: 10–20 nm); liquid: deionized water;PLR ¼ 2.5 g mL�1)) increased with increase in the tempera-ture of the slurry (Tsl) (15�C � Tsl � 37�C),103 consistentwith 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).


Summary. The methods used for characterizing the visco-elastic properties of CPCs are the same as those used forABCs. More research attention has been given to the influ-ence of extrinsic factors on the viscoelastic properties ofCPC than to the influence of intrinsic factors. Studies onmodeling any viscoelastic property of a CPC are lacking.

AREAS FOR FUTURE STUDY

Five areas for consideration for future study arepresented.

The first is to perform detailed systematic parametricstudies such as (1) influence of an antibiotic on the creepdeformation of a PMMA bone cement, obtained using fullyconstrained specimens subjected to dynamic loading; and(2) the influence of intrabatch and interbatch variability onthe dynamic viscosity-versus-time and damping properties(storage modulus-versus-t, loss modulus-versus-t, and lossfactor-versus-t) of a given commercially available acrylicbone cement used for TJRs.

The second area is to develop testing standards fordetermining various viscoelastic properties of ABCs, CPCs,and CSCs. A principal aspect of each of these standardsshould be a detailed definition of the combination of loadingmode and environmental conditions that simulate clinicalconditions. 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 thecement useful for clinical application. For example, it wassuggested that, for PMMA bone cements to be used in VP,the viscosity of the dough upon insertion into the fracturedvertebral body should be in the range of 100–200 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, havereceived little attention. Three such types of cements are rec-ognized. The first is the new generation of ABCs that addressone or more of the long list of drawbacks of commerciallyavailable ABCs (in the literature, this new generation ofcements has been designated ‘‘alternative acrylic bonecements’’).107 Recent examples of alternative acrylic bonecements are (1) a cement that contains a methacrylate whoselower toxicity is lower than that of MMA; specifically, theprincipal liquid constituents for the new cement are 2-ethyl-hexyl methacrylate (EHMA) and trimethylolpropane whilepoly(EHMA/cyclohexyl methacrylate) beads is the principalpowder component108; (2) a cement comprising copolymersof MMA and lauryl methacrylate, in the ratio 1:1 v/v, wasconsidered suitable for use in BKP109; (3) a cement compris-ing a new class of radiopaque monomer using a copolymerbased on MMA and GMA that is made radiopaque by theepoxide ring opening of the GMA, followed by the covalentattachment of elemental iodine110; (4) a PMMA cement rein-forced with variable-diameter ZrO2 fibers111; (5) a PMMAcement that has reduced toxicity and added osteoconductivitythrough the incorporation of N-acetyl cysteine in the liquidmonomer112; and (6) a PMMA that is reinforced with TiO2-SrO nanotubes that are functionalized using a monomericcoupling agent (methacrylic acid).113

The problem of reduced efficacy of antibiotic-loadedPMMA bone cements (ALBCs) arising from increasing resist-ance of the relevant microorganisms (such as Staphylococcusaureus) 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 suitabilityof 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 thathas been shown to be very effective against a number ofmicroorganisms in various patient populations, such as diffi-cult bone and joint infections caused by methicillin-resistantStaphylococcus epidermidis.115 Thus, an example of this newgeneration of ALBCs (which constitutes the second group ofIBCs for future study) is a daptomycin-loaded PMMA bonecement, for which some in vitro properties have beendetermined.116

The third group of IBCs are those that do not have thedrawbacks of cements that are currently being used for VPand BKP; for example, modulus and strength being signifi-cantly greater than the corresponding values for osteopor-otic cancellous bone (PMMA bone cements) and poor inject-ability (CaP cements). Recent examples of this newgeneration of IBCs that may find use in VP and/or BKP are(1) a bioactive calcium aluminate cement117; (2) a reduced-modulus PMMA bone cement achieved through manual mix-ing of a 10% solution of hydroxypropylmethyl cellulose(45–50% aqueous volume fraction) with the PMMA118; (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 serveas initiator of the free radical polymerization reaction andDMPT added to the other to serve as activator/acceleratorof that reaction) that is modified by incorporation of eitherZrO2 microspheres or nanospheres (20 wt %)81; (4) aniron-modified a-tricalcium phosphate-CaSO4 dihydratecement119; (5) a Sr-containing carbonate apatite cement, inwhich the powder constituents are calcium hydrengeno-phosphate dihydrate, CaO, and SrCO3, and the liquid constit-uent is 0.75M ammonium phosphate120; (6) a partiallyresorbable composite of CaSO4 and HA121; and (7) an alumi-num-free, zinc-based glass polyalkenoate cement.122

The fourth area for future research is to expand thedatabase on viscoelastic properties of IBCs that, to date,have not been studied; namely, CSCs for use in VP and BKP,filamentary composite materials for use in VP and BKP,and injectable bone void fillers/bone graft substitutes.Recent examples of the materials that may find use in thelast-mentioned applications include (1) a calcium sulfate-HAcomposite123; (2) CaCO3-CaP cement, comprising at least40 wt/wt % CaCO3 in the powder124; (3) a CaP-20% massfraction chitosan composite125; (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(CaSO4.0.5H2O)).

127

The fifth area is to perform studies on modeling thecreep and stress relaxation of newly developed IBCs. For

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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 ofinjectable bone cements for use in orthopaedic appli-cations may be characterized as modest, with the pre-ponderance of the work being on creep, damping, andviscosity-time characteristics of plain acrylic bonecements for use in anchoring total joint replacements.

2. Although there have been many studies on the influenceof a host of variables on various creep performancemeasures of acrylic bone cements, the presence of con-founding variables in many of these studies makes it dif-ficult to make definitive statements on the nature ofmost of these influences.

3. For an acrylic bone cement, a number of important con-tributions have made in modeling its creep and a widecollection of empirical relationships have been obtainedfor both its creep and stress relaxation.

4. For an acrylic bone cement, powder particle size distri-bution, test temperature, and test frequency are some ofthe variables that appear to exert marked influence onits damping behavior.

5. For an acrylic bone cement, there is indication that incor-porating certain additives has a clear influence on theviscosity of the curing cement.

6. The literature is either deficient or lacking in studies ofviscoelastic properties of a number of IBCs, such as thenew generation of PMMA bone cements that aredesigned to supplant commercially available ones, antibi-otic-loaded PMMA bone cements, calcium phosphate-based cements, calcium sulfate-based cements, and bonevoid fillers/bone graft substitutes.

7. As a result of observations given in items (2), (4), (5),and (6) above, opportunities abound for future researchin the field of viscoelastic properties of IBCs for ortho-paedic applications, with examples being determinationof the influence of mixing method on damping propertiesof ABCs for use in total joint replacements, developmentof standards for the determination of viscosity of calciumphosphate cements for use in balloon kyphoplasty, andmodeling of the stress relaxation of calcium sulfatecements.

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