Materials Science and Engineering C 69 (2016) 1328–1334

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Materials Science and Engineering C

journal homepage: www.elsevier.com/locate/msec

Acrylic bone cement and starch: Botanical variety impact on curing

parameters and degradability
Céline Aubrun-Fillâtre, Francine Monchau, Philippe Hivart ⁎
Equipe Biomatériaux Artois, Laboratoire de Génie Civil et géoEnvironnement (LGCgE EA4515), Université d'Artois, Béthune, France

a r t i c l e i n f o a b s t r a c t

Article history: Acrylic bone cements are a conventional solution to heal bone defects. Starch is often added to the cement to
Received 13 June 2016 improve its degradability and resorbability. The most used botanical variety is corn starch; few studies or
Received in revised form 18 July 2016 applications deal with other varieties. This study focuses on classical formulations based on 2-
Accepted 8 August 2016
hydroxyethylmethacrylate but incorporating different starches: waxy maize, corn, amylo maize, wheat, pea or
Available online 9 August 2016
potato, with or without enzyme (α-amylase).
Keywords:
A thermocouple is used to determine the curing parameters: setting time and maximal temperature. The water
Bone cement uptake depends on the cement immersion time in a biological fluid and it is studied through sample mass vari-
HEMA ation analysis. The weight loss is determined after immersion (function of the time) and drying.
Starch Starch botanical variety and enzyme presence do not impact curing parameters and water uptake but strongly
Curing parameters influence degradability. Water uptake involves advantageous swelling in situ filling the defect. This study
Degradability shows that starch accessibility by the enzyme explains this impact. Grain spatial configuration, specific surface
area and starch distribution in cement give a complementary explanation of the well-known influence of the
ratio amylopectin/amylose. Acrylic cements incorporating starch can be classified according to their
degradability.
© 2016 Elsevier B.V. All rights reserved.

1. Introduction 1.2. Acrylic cement

1.1. Bone cements: context
Bones may present pathological or trauma defects. These ones can
be filled by natural or synthetic bone substitutes [1,2]: scaffolds (rigid
or flexible bulk materials) or cements (taking the defect shape and us-
able for sealing). Cement is composed by a liquid phase and a solid
phase; after mixing, they set and harden. The liquid phase nature
leads to differentiate mineral hydraulic cements such as calcium phos-
phate cements [3] and polymer cements [4,5]. Polymer cements have
shorter setting time and better mechanical properties than the hydrau-
lic ones. Used for sealing hip prostheses since the 1960s, [5–7] acrylic
polymer cements are now also used to fill bone defects issued for in-
stance from osteoporosis, primary or secondary tumors or fractures
[8–11]. These acrylic cements are injectable and compatible with percu-
taneous techniques. They harden in situ and fill perfectly the bone de-
fect. [12]. This technique allows safer surgery with fewer risks for the
patient. Thus, cement is a very interesting surgery solution.
⁎ Corresponding author at: IUT/GMP, 1230, rue de l'Université, CS 20819, F-62408
Béthune Cedex, France.
E-mail address: philippe.hivart@univ-artois.fr (P. Hivart).
Most commonly used bone cements are composed of methyl meth-
acrylate (MMA) for the liquid phase and of polymethyl methacrylate
balls (PMMA) for the solid phase. This formulation has some disadvan-
tages: non-resorbability [13], shrinkage after polymerization which can
lead to implant loosening and fibrous tissue development [14,15], exo-
thermic reaction [16] which can damage surrounding tissue.
Many researches aim to improve cements properties, especially
resorbability. Indeed, after bone defect filling, this property consists in
the progressive cell colonization of the cement and its replacement by
a new bone tissue [11,17].
Various elements [8] can be added to the solid phase, for instance:
barium sulfate or zirconium oxide (radio-opacifiers), ceramic
(tricalcium phosphate TCP, hydroxyapatite HA) or bioglasses [18]
(osteoconductivity) or mixture starch (biodegradability) - cellulose ac-
etate (mechanical properties) [4].
The liquid phase can also be significantly modified, particularly by
substitution of all or part of MMA with another monomer, for instance
acrylic acid, styrene, lactic acid or 2-hydroxyethylmethacrylate [8,19,20].
Formulating cement with this last one (HEMA) [4,19,21]
strengthens its biodegradable nature and remove shrinkage problem.
HEMA gives swelling properties to the cement [22,23] while maintain-
ing desirable properties of PMMA cements: rapid polymerization,

http://dx.doi.org/10.1016/j.msec.2016.08.023
0928-4931/© 2016 Elsevier B.V. All rights reserved.
 C. Aubrun-Fillâtre et al. / Materials Science and Engineering C 69 (2016) 1328–1334 1329

injectability and good mechanical properties. This improvements lead Table 2

to a new cement class: hydrophilic, partially degradable and bioactive Initial characteristics of starch grains.

acrylic cements (HDBCs) [4]. Amidon % % Average grain Specific surface Supplier
variety amylose amylopectin size (μm) area (m2·g−1)
1.3. Studied cements: HEMA and starch Amylo 60 40 7.10 0.30 Roquette,
maize France
Among the possible components, starch is particularly interesting Corn 25 75 13.45 0.65
Waxy 1 99 15.70 0.75
because leading to cement resorbability. Indeed, starch can be degraded
maize
by an enzyme, the α-amylase present in human body [24]. It is com- Pea 35 65 18.20 0.67
monly used for bone substitutes [25,26] or drug delivery system [27] be- Wheat 25 75 18.86 0.30
cause of this property. This is consequently a solution widely studied [4, Potato 20 80 45.48 0.20
19,28–30]. α-amylase may be initially incorporated into the cement:
starch and thus the cement are more effectively degraded [31–33]. Po-
rous network created by starch resorption can be used by osteocytes:
by colonizing cement they are in contact with incorporated ceramics
fillers [34]. starch is visible by impregnation of fresh section with iodinated water
However, most studies, to our knowledge, focus on corn starch, (Lugol's liquor, Panreac, Germany). Through binocular device, starch
modified (e.g. gelatinized or acetylated) or not [19]. Indeed, corn starch distribution appears with a purple coloration.
is widely produced and used on Earth although many other varieties Cement is prepared by adding liquid phase to solid phase then hand
exist. However using starch from amylo maize, corn, waxy maize, pea, mixing in silicone mold. A formulation is developed with or without en-
wheat and potato allows varying amylose/amylopectin rate, particle zyme for each starch variety. For each, three samples are made at least.
size and specific surface area [35]. Starches with different characteristics Cements are designated by plant initial (Am: amylo maize, Co: corn,
are so an interesting way. Wa: waxy-maize, Pe: pea, Wh: Wheat, Po: potato), preceded by letter
We so study in this paper starch botanical variety impact on several E if enzyme.
properties of acrylic bone cement formulated with HEMA, with or with-
out α-amylase: curing parameters, water uptake, and degradation
through weight loss in biological fluid. These parameters are usually 2.2. Cements characterization
taken into account for the study of bone cements and commonly appear
in literature. Indeed they are important parameters for cements de- The study concerns cement curing parameters (setting time and
signed for surgical applications. maximum temperature reached) and sample behavior (after curing)
in biological fluid (water uptake and weight loss).
2. Materials and methods
2.2.1. Curing parameters
2.1. Cements formulations A type T thermocouple (a copper wire and a constantan wire) is
placed in the center of a silicone mold (diameter 10 mm, height
Formulations commonly used for biodegradable cements [18,19,22, 15 mm). After mixing, cement is poured in this mold. In order to get
23] are chosen for this study. 2-hydroxyethyl methacrylate (HEMA, rid of lab temperature variations, mold and components are initially
Acros Organics, USA) composes the liquid phase of our acrylic cement. kept at 10 °C in a cooled enclosure. Each second cement temperature
Dimethyl-p-toluidine (DMT, Acros Organics, USA) and benzoyl peroxide during cure is measured through the thermocouple connected to a ded-
(BPO, Acros Organics, USA) are respectively polymerization activator icated device (datalogger portable USB, YCT).
and initiator. Solid fillers are added to this liquid phase constituting Drawn temperature curves allow to determine maximum tempera-
the cement binder. Solid/liquid (S/L) ratio is 60/40 by mass. Solid ture reached by cement during cure (Tmax) and setting time (ts) [37].
phase is composed (by mass) of 50% tricalcium phosphate, a bioactive Setting time is time required for cement to reach its average tempera-
calcium phosphate ceramic powder (TCP, Acros Organics, USA), 25% cel- ture: arithmetic average of maximum temperature and ambient tem-
lulose acetate (Acros Organics, USA) and 25% starch (Roquette, France). perature. Tmax and ts are curing parameters.
Our aim is to study starch botanical variety impact. So each formulation For each formulation, three curves at least are plotted.
is composed of starch issued from a different plant [36]: amylo maize,
corn, waxy maize, pea, wheat and potato. BPO is incorporated to solid
phase at a molar concentration of 0.001 with respect to the HEMA 2.2.2. Water uptake and weight loss in biological fluid
amount, and DMT to liquid phase at a molar concentration of 0.67 Cement samples (pellets diameter 15 mm, height 2 mm) are im-
with respect to the BPO amount. For use, TCP is calcined for 9 h at mersed (static test) in simulated body fluid (SBF) at 37 °C, up to
900 °C. Enzyme is bacillus licheniformis α-amylase (500 units·ml− 1, 6 weeks.
Sigma Aldrich, France), added to liquid phase just before cement mixing To determine water uptake (WU), a sample is weighed (after being
(1.6% of HEMA mass; [19,30]). out of SBF, rinsed with distilled water and blotted with filter paper) then
Cement components characteristics are given in Tables 1 and 2. Fig. 1 replaced in SBF. This protocol is realised on days 1, 2, 3, 4, 6, 7, 14, 21 and
gives grain shape and grain size of starch powders. After cement curing, 42 over the 6 weeks. Each time, water uptake is determined (Eq. (1))

Table 1
Molar mass and volume of components of studied acrylic cements.

Component Molar mass g·mol−1 Density g·cm−3 Average grain size (μm) Specific surface area (m2·g−1) Supplier

Cellulose acetate 60.05 1.37 264.20 6.73 Acros Organics, USA

TCP (calcined) 127.88 3.19 2.29 2.48
BPO 242.23 1.33
DMT 135.21 0.93
HEMA 130.14 1.07
1330 C. Aubrun-Fillâtre et al. / Materials Science and Engineering C 69 (2016) 1328–1334
Fig. 1. Starch grains issued from several plants (SEM).
and a curve WU - immersion time is plotted.
WU ¼ ½ðmti −mi Þ=mi   100
mi initial mass (before first immersion).
mti pellet mass after i immersion days.
To determine weight loss (WL), cement samples are taken at 7, 14
and 21 days, dried in an oven at 37 °C for 24 h and then in a desiccator
for 24 h (Orange Indicating Silica Gel, AGM, USA). Samples are weighed
to determine WL (Eq. (2)) and a curve WL - immersion time is plotted.
WL ¼ ½ðmi −m f Þ=mi   100
mi initial mass (before first immersion).
mf final mass after drying.
3. Results and discussion
3.1. Curing parameters
Temperatures measured for each cement without enzyme during
cure (Fig.2) and curing parameters (Table 3) show that studied starch
varieties have very few influence. Indeed, temperature-time evolutions
are similar, as well as maximum temperature (about 70 °C) and setting
time (about 5 min).
Fig. 2. Temperature evolution during cure (cements without enzyme).
Tests with enzyme show same results and therefore no impact on
curing parameters.
ð1Þ Values are consistent with those reported in literature. Commercial
cements currently used for orthopedic applications, primarily formulat-
ed with PMMA, lead to a maximum temperature between 55 and 90 °C
and even above 100 °C and setting time between 3 min and more than
10 min [22]. HEMA based cements studied in different articles lead to a
maximum temperature between 77 and 96 °C for a setting time be-
tween 1 and 4 min [4,19].
If handling time remains appropriate to clinical surgical applications
needs, maximum temperature should ideally be below tissue necrosis
temperature, 47 °C according to some studies [38,39]. In our case, tem-
ð2Þ
perature is above 47 °C only for a maximum period of 2 min. This time is
permissible for some authors who consider that, from a point of view of
energy, temperature and duration are linked and must be simulta-
neously taken into account [40,41].
It is logically advocated to increase S/L ratio [16] because liquid
phase determines cure and temperature rise. Other authors make use
of retarders such as hydroquinone [42–44]. Nevertheless, our results,
for constant S/L ratio, allow asserting that starch botanical variety
does not affect maximum temperature.
3.2. Water uptake
Water uptake curves (Fig.3, without error segments to improve clar-
ity) show that cement is filling by liquid from first immersion days,
 C. Aubrun-Fillâtre et al. / Materials Science and Engineering C 69 (2016) 1328–1334 1331

Table 3 loss is more important for formulations with enzyme. Without enzyme,
Maximum temperature (Tmax) and setting time (ts; cements without enzyme). it is less than 5% whereas with enzyme it varies from 9.18% to 20.14% on
Am Co Wa Wh Pe Po day 21. Moreover, weight loss, different for each starch, shows that each
Tmax (°C) 68.03 69.57 67.93 73.33 71.80 73.37
one reacts differently to enzymatic attack. Waxy maize and pea starch
SD (°C) 3.36 5.88 4.10 0.51 3.98 2.33 are more quickly and most degraded by enzyme whereas potato starch
ts 5 min 33 s 4 min 57 s 4 min 59 s 4 min 49 s 5 min 7 s 4 min 49 s is much less degraded.
SD (s) 5.03 1.53 4.62 11.02 7.00 9.29 Starches are made up of molecules of D glucose bonded to each
other, their difference being in bond type [47]. Glucosidic bonds α-
(1,4) lead to a linear polymer called amylose, while α-(1,6) lead to a
regardless of formulation. Sample mass increases by more than 30% by branched polymer called amylopectin. Starch is composed of these
24 h. During this period, the enzyme presence in cement does not im- two polymers, the ratio depending on botanical variety (Table 2).
pact. However, this enzyme leads to starch degradation and thus to a ce- Depending on their type and on their own mode of action, enzymes
ment weight loss (showed below), so, it explains the few decrease after attack one or the other of these bonds. The endo-enzyme used in this
24 h for the cements with enzyme (Fig.3b). Afterwards the evolution is study is α-amylase Bacillus licheniformis, allowing the α-(1,4) bond hy-
similar in both cases, with or without enzyme, as well as obtained WU drolysis. This enzyme attacks sequentially and randomly but it is
values. This mass increase by hydration leads to swelling. Should be stopped by α-(1,6) bond, constraining to go to another site [48]. This
noted that cement cure conditions do not allow, in our case, starch mod- enzyme is selected for this study because it withstands temperature
ification which could cause such swelling [45]. HEMA, hydrophilic [4], is [49] and it is the same type as an enzyme present in human body, unlike
here the main cause of this variation. This swelling is advantageous for β-amylases for example.
implantation in bone site. It allows to fill bone defect whereas shrinkage However Fig. 5a shows that weight loss increases with amylopectin
(PMMA-based cement for example) [15] promotes deleterious fibrous percentage (except for potato starch) whereas α-(1,6) bonds are not af-
tissue development at the bone-cement interface [46]. fected by enzyme. This apparent paradox comes from deterioration in
Therefore, in our study case, starch botanical variety does not affect enclosed space: enzyme cannot easily migrate across the cement. A
water uptake. first contact starch/enzyme is necessary. Even owning more α-(1,6)
bonds, not attackable by the enzyme, amylopectin, with a branched
3.3. Weight loss structure, provides more attack and binding sites than amylose, with a
linear structure [47].
Weight loss curves (Fig.4) show strong impact of adding α-amylase In addition, grains with larger amylose proportion are smaller and
to the cement. For each formulation, regardless of starch variety, weight thus more spaced into the material (Fig.5b). Potato starch case shows

WU (%) a

30

20

10

Time (days)
0
0 10 20 30 40

WU (%) b

30

20

10

Time (days)
0
0 10 20 30 40

Fig. 3. Cement water uptake (WU) as a function of immersion time in SBF: a. without α-amylase, b. with α-amylase.
1332 C. Aubrun-Fillâtre et al. / Materials Science and Engineering C 69 (2016) 1328–1334

WL (%)

20

10

without enzyme
sans enzyme with
avec enzyme

Time (days)
0
0 7 14 21

Fig. 4. Cement weight loss (WL; with or without α-amylase) as a function of immersion time in SBF.

that it is about accessibility factor: degradation increases with specific Fig. 6 confirms our hypothesis through visualization of starch grains
surface area (Fig.5c). This phenomenon is similar to the one known in distribution for the two extreme cases (waxy maize and potato). En-
literature as percolation threshold [19][30]. zyme action depends on temperature and environment [50]. Our tests

WL (%) a
20

10

Amylopectin (%)
0
0 20 40 60 80 100

WL (%) b
20

10

Average diameter of starch grains (μm)

0
0 10 20 30 40 50

WL (%) c
20

10

specific surface area of starch grains (μm)

0
0.0 0.2 0.4 0.6 0.8

Fig. 5. Cements (with α-amylase) weight loss according to starch characteristics: a. % amylopectin, b. grain size, c. specific surface area.
 C. Aubrun-Fillâtre et al. / Materials Science and Engineering C 69 (2016) 1328–1334
Fig. 6. Distribution of starch grains in a freshly cut cement sample (with α-amylase): (Wa: waxy maize, Co: corn, Po: potato, test Lugol®): - before immersion in SBF (Wa 0, Co 0 and Po 0), -
after a week of immersion (Wa 7, Co 7 and Po 7).
have however shown that cement temperature and its evolution are al-
most the same for all studied starches, during cure and later in the same
environment, and even buffered for SBF. In our case, temperature and
environment settings are not explanatory factors.
Potato starch grains have the highest average diameter and a high
amylopectin percentage. This starch leads to very low weight loss.
This is an effect due to low accessibility with a joint effect of particle
size and distribution.
Amylo maize starch grains have the lowest average diameter but
also lead to a low cement weight loss. This effect is due to amylose pro-
portion and α-(1,6) bonds. A low quantity of α-(1,6) bonds leads to few
branching, unfavourable to the encounter enzyme-starch.
Our results show that the highlighted accessibility factor covers sev-
eral concepts.
Enzyme and starch concentrations and grains size determine en-
counter statistical probability, meaning accessibility of enzyme to
starch.
Specific surface area conditions access to amylopectin and amylose
of the starch grain. It has to do with grain surface state, variable accord-
ing to botanical origins. Glucosidic bonds type and structure determine
starch grain degradability.
Additive effects indeed explain different cements behaviours.
For degradable cement, accessibility to starch is a key factor, objec-
tive being to achieve percolation threshold. It consists to obtain contin-
uous starch network into the cement. On the one hand, enzyme can
access to starch gradually as it is degrading. On the other hand this deg-
radation leads to interconnected porous network formation facilitating
material colonization by bone cells.
These tests guide choice towards starch with high amylopectin per-
centage, low grain size and high specific surface area. This properties in-
crease encounter probability with endo-enzyme, α-amylase. In our
conditions and for our formulations, waxy maize leads to the best starch
to be used in our cement.
4. Conclusion
The study of acrylic bone cements formulated with HEMA and incor-
porating starch in solid phase brings out little starch botanical variety
impact (amylo maize, corn, waxy maize, pea, wheat, or potato) on cur-
ing parameters, with or without enzyme (α-amylase). Setting time is in
any case about 5 min and maximal temperature is about 70 °C. These
data are consistent with those reported in literature, and their values
are average.
1333
Starch botanical variety has also small impact on water uptake. En-
zyme presence slightly modifies these parameters, but overall, in all
cases, mass increase is similar, and about 30% on average. With mass in-
crease we observe a swelling. This property, whatever the starch, allows
to avoid space between cement and bone tissue and fibrous tissue de-
velopment at the interface.
However, starch nature and enzyme presence or absence have
strong impact on cement degradability and on cement resorbability
properties. The study shows that accessibility factor of enzyme to starch
predominates, even more in our case, enzyme accessibility to α-(1,4)
bonds. Grains shape, size and distribution, spatial amylose and amylo-
pectin configuration and specific surface area offset usual reasoning,
based on single amylopectin/amylose ratio. This ratio proves to be the
third factor in influence order on cement degradability.
Optimum will also be:
– fine particles in large number (low average diameter, maximized
statistical dispersion),
– surface state able to promote enzymatic attack (macro/microporos-
ity or starch enzymatic pretreatment),
– highest amylopectin percentage.
Most favorable to this degradation is waxy maize. Its amylopectin
percentage and its specific surface area are the highest among those
studied, for an average diameter grain.
Using other starches than conventional and commonly used, i.e. corn
starch, so allows to adapt rate and kinetic of degradation. Cement can be
adapted to a given clinical use. Choice can thus be turned to other
starches that will be both more accessible by enzyme because of their
spatial configuration (size and porosity for example) and more able to
be hydrolysed.
Acknowledgements
The authors are thankful to Roquette compagny, and particularly to
Mr. Thierry Feron, Head of Customer Technical Services - GBU Industry,
for providing graciously the different commercial starches used in this
study.
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Céline Aubrun-Fillâtre (Physical and chemistry graduated
teacher) is preparing a PhD in mechanical engineering at
the Équipe Biomatériaux Artois of the Laboratoire Génie Civil
et géoEnvironnement (Université d'Artois). She specialized in
biomaterials in the field of bone acrylic cements.
Francine Monchau is an assistant professor at Université
d'Artois. She is specialized (Équipe Biomatériaux Artois of the
Laboratoire de Génie Civil et géoEnvironnement) in the field
of calcium phosphate bone substitutes. She is a teacher in
materials science at Institut de Technologie de Béthune.
Philippe Hivart is founder and head of the Équipe
Biomatériaux Artois of the Laboratoire de Génie Civil et
géoEnvironnement (EA 4515). Specialized and teacher in me-
chanical engineering, he is developing researches on tech-
nology for health care at Université d'Artois.