CaCO3 vaterite microparticles for biomedical and personal care applications

Materials Science and Engineering C 45 (2014) 644–658

Contents lists available at ScienceDirect

Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec

CaCO3 vaterite microparticles for biomedical and personal care applications Daria B. Trushina a,b, Tatiana V. Bukreeva c,d, Mikhail V. Kovalchuk c,d, Maria N. Antipina a,⁎ a

Institute of Materials Research and Engineering, A*STAR, Singapore 117602, Singapore Lomonosov Moscow State University, Faculty of Physics, Moscow 119991, Russia National Research Centre “Kurchatov Institute”, Moscow 123098, Russia d A.V. Shubnikov Institute of Crystallography, Moscow 119333, Russia b c

a r t i c l e

i n f o

Article history: Received 16 January 2014 Accepted 21 April 2014 Available online 14 May 2014 Keywords: Calcium carbonate (CaCO3) Biomineral Vaterite polymorph Co-precipitation Crystal growth

a b s t r a c t Among the polymorph modifications of calcium carbonate, the metastable vaterite is the most practically important. Vaterite particles are applied in regenerative medicine, drug delivery and a broad range of personal care products. This manuscript scopes to review the mechanism of the calcium carbonate crystal growth highlighting the factors stabilizing the vaterite polymorph in the most cost efficient synthesis routine. The size of vaterite particles is a crucial parameter for practical applications. The options for tuning the particle size are also discussed. © 2014 Elsevier B.V. All rights reserved.

1. Introduction Vaterite is a mineral, a polymorph of calcium carbonate (CaCO3). Vaterite is usually colorless, having spherical shape and porous inner structure. The diameter of a vaterite particle ranges from 0.05 to 5 μm. Like aragonite, vaterite is a metastable phase of CaCO3 at ambient conditions at the surface of the earth. Being less stable than either calcite or aragonite, vaterite has a higher solubility than either of these phases. Therefore, vaterite transforms to calcite or aragonite once it is exposed to water. Temperatures below 60 °C facilitate the formation of calcite, and at the higher temperatures, recrystallization to aragonite occurs [1,2]. Despite being metastable, vaterite can still be found in nature, for instance, in mineral springs. It usually occurs as a minority component of a larger structure or as a result of a pathological process in humans and animals. Thus, vaterite is found in fish otoliths, freshwater pearls, healed scars of some mollusk shells, gallstones and urinary calculi [3]. In those circumstances, some impurities (metal ions or organic matter) may stabilize the vaterite and prevent its transformation into calcite or aragonite. Like other polymorphs of calcium carbonate, vaterite rapidly dissolves at acidic pH, and thus it can undergo degradation both in vivo

⁎ Corresponding author. Tel.: +65 68741974; fax: +65 68720785. E-mail address: [email protected] (M.N. Antipina).

http://dx.doi.org/10.1016/j.msec.2014.04.050 0928-4931/© 2014 Elsevier B.V. All rights reserved.

and in vitro. Biodegradation of vaterite may occur in body fluids or some acidic extracells, or upon the cellular phagocytosis and absorption. Body fluid contains a number of acidic metabolites, such as citrate, lactate and acid hydrolysis enzymes, which provide acidic environment for dissolution of the material. After entering cells (mainly macrophages) by phagocytosis, vaterite particles are split into ions under the effect of cytoplasmic and lysosomal enzymes, and then the degradation 2+ products, Ca2+ and CO2− can then 3 , can be transferred to extracell. Ca participate in the formation of new tissue without causing organic damage and pathological tissue calcification [4]. Vaterite microparticles can be produced in a number of ways, however, the majority of them is laborious, or requires extreme conditions and special equipment. The main industrial manufacturing method is based on CO2 bubbling through a calcium containing solution, also referred as the Kitano approach [5–8]. Among the other popular methods are the double emulsion approach [9], solvothermal growth in autoclave above 100 °C [10], and biomineralization [4,11,12]. Synthesis is often carried out in a double jet reactor vessel [13] applying ultrasound [14–16] or magnetic field [14,17,18]. The simplified method comprises mixing of saturated aqueous stock solutions containing calcium and carbonate ions. The mixing method is highly cost efficient, fast and easy to perform. Moreover, it may be scaled up for industrial production of vaterite particles [19–23]. However, the mixing method may result in unwanted recrystallization of vaterite to more stable polymorphs of calcium carbonate. Therefore, a detailed understanding of the CaCO3 crystal growth process is essential for the success in vaterite production.

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Here we introduce the current opinions on the vaterite crystal growth and review the conditions promoting the vaterite polymorph of calcium carbonate. Due to its biodegradability, low cost and unique physical and chemical properties, vaterite is highly demanded in biomedicine and is an essential component of a big variety of personal care products. Besides being actively used in bone implants, abrasives, cleaners and absorbers, vaterite is playing a key role in encapsulation and drug delivery. However, the size of the vaterite particles is often a crucial parameter. Possible ways to influence the particle size are also discussed in the manuscript. 2. Introduction to the CaCO3 crystal growth The formation of a new solid phase is initiated through nucleation in supersaturated solution. Solid state precipitates initially in an amorphous sediment of spherical granules with a diameter of 10 nm– 70 nm [5,17,19,20,24,25]. Then, the transformation and dissolution– recrystallization processes result in a mixture of calcium carbonate crystalline hydrated forms (hexahydrate and monohydrate) and three anhydrous crystalline polymorphs (vaterite, aragonite and calcite). Vaterite nucleation and growth are of special interest, and the vaterite particle formation mechanism is a subject of on-going debate [25]. Two explanations for the formation of primary polycrystalline vaterite spheres exist in the literature. The nano-aggregation concept claims that the spheres are the result of rapid aggregation of initially formed nano-sized crystals [6,16,22,26,27]. However, only relatively insoluble substances develop high supersaturations, so that precipitation can also be considered as crystallization of sparingly soluble substances. Thus, the concept of classical spherulitic growth shown schematically

Fig. 1. Stages and pathways of precipitation processes [15].

645

in Fig. 1 advocates that a sphere of vaterite with polycrystalline features originates from the formation of a single nucleus followed by branching of this small crystal (often mentioned as ripening of crystallites) [26,28, 29]. It is also supposed that a final particle can be a result of both crystallization processes taking place at a time [30]. According to the crystal growth theory, precipitation starts from nucleation. The initially formed nuclei grow into crystallites. The crystal growth process occasionally entailed with the formation of secondary nuclei causes significant changes in the initial concentrations of calcium and carbonate ions in solution. The crystal growth itself is a complex process comprising two elementary processes taking place either at some distance from the crystal surface or at the crystal–solution interface. These elementary processes are 1) diffusion and/or convection of growth units through the bulk towards the crystal–solution interface, and 2) surface integration processes at the crystal–solution interface. The slowest of these consecutive processes determines the overall crystal growth rate. The solid phase thus formed (crystals) undergoes further changes in physical and chemical properties. These secondary changes occur under conditions close to equilibrium signifying the tendency of the system to establish equilibrium. Theoretically, precipitation terminates when the crystals present in the system form one crystal which is in equilibrium with the saturated solution. In practice, precipitation is completed when crystals reach a size that causes sedimentation. The process that leads to equilibrium is called ageing and takes place through several possible ways. Dissolution of small and simultaneous growth of large particles (also referred as Ostwald ripening) and recrystallization are the mechanisms that probably always occur in the early stages of the precipitate formation. Coagulation and agglomeration followed by sintering change the initial dispersion of the system by the formation of more stable large aggregates (Fig. 1). The preference for vaterite formation exists when starting ionic activity productIAP ¼ aCa2þ  aCO2− lies between thermodynamic solubility 3 product for amorphous calcium carbonate KSP(ACC) and the solubility product for vaterite KSP(Vaterite) [26]. The logarithmic ion activity product of Ca2+ and CO2− 3 in the suspension at 25 °C is shown as a function of time in Fig. 2a. Regions I, II and III in Fig. 2 correspond to unstable stage, metastable stage and stable stage, respectively. Under condition within the region I (unstable stage), calcium carbonate nanoparticles randomly emerge as an amorphous sediment at all temperatures. Onwards, nanoparticles line up along specific crystallographic orientations, resulting in a phase change from poorly crystalline to crystalline. The crystalline CaCO3 begins to form around the time when the IAP curve shows the “inflection point” (Fig. 2a) [19]. As the crystals continue to precipitate, the supersaturation status decreases causing the nucleation force to decrease as shown in Fig. 2b, and the subsequently formed nanoparticles begin to attach to each other in a crystallographically oriented fashion, which is thermodynamically more stable than random attachment. The transformation of amorphous calcium carbonate (ACC) is completed just before the steep decrease in the IAP, and all ACC particles disappear forming clusters a few micrometres in diameter. The polymorph composition of precipitated particles in the early metastable stage was presented as a function of temperature in Fig. 3. Initial ACC transformed to the combination of vaterite and calcite at low temperatures (14 °C to 30 °C). Vaterite polymorph occurs predominantly at 30 °C–40 °C. At intermediate temperatures (40 °C to 50 °C) the formation of all three polymorphs is observed. Elevating the temperature above 60 °C stabilizes aragonite polymorph of calcium carbonate. The abundance of a certain modification also depends on supersaturation [11,13,19,26]. The effect of supersaturation has been described by the Ostwald's law of stages: at sufficiently high supersaturation the most soluble and the least stable form crystallizes first [32]. At the beginning of the stage II, the system is supersaturated with respect to all polymorphic forms, thus the least stable and higher-energy form of vaterite is the first to crystallize. The crystallization of the vaterite

646

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Fig. 2. The change in logarithmic ion activity product of calcium and carbonate, log IAP, with time at 25 °C (a) (plotted from [19]); the dependence of nucleation rate on supersaturation (b) (plotted from [31]).

form will proceed until the supersaturation value decreases down to reach the solubility for this form (Fig. 4a). At the same time, as the system is supersaturated with respect to all forms, the crystallization of the second more soluble form (aragonite) begins. Dissolving vaterite contributes to further crystallization of the aragonite form until completely transformed [32]. Complete dissolution of vaterite induces steep decrease in the IAP value to Ksp of the next polymorph (aragonite) with subsequent transformation to the most stable calcite [19]. Fig. 4b provides a range of respective Ksp values for the vaterite, aragonite and calcite forms at different temperatures. It can be seen from Fig. 4b that the solubility product of all forms decreases at the higher temperatures that is quite uncommon for both organic and inorganic substances. As the vaterite form has the highest solubility among the polymorphs and precipitates first, it appears to be the most challenging to stabilize its nuclear and suspend the formation of other modifications. During the metastable stage, all crystals are finally transformed to the most stable modification of calcite at all temperatures as a result of water induced dissolution–recrystallization process, Fig. 5. The implication of the theory reveals that by controlling the supersaturation and harvesting crystals at an appropriate time, it should be possible to isolate the certain polymorphic form [32]. The stable stage corresponds to particle growth in size without further changes in morphology. The value of IAP stabilizes at the solubility

product of calcite and nuclei grow persistently up to a certain size (Fig. 2a) [23]. Factors influencing the morphology of CaCO3 crystals are those affecting supersaturation. The activity of the calcium and carbonate ions is connected with the ionic strength and temperature. As shown in Fig. 6, the time required to reach the metastable stage (Tm) of the polymorph mix decreases with increasing temperature. Temperature is an important parameter for bulk crystallizations as it allows to control the product solubility making it possible to obtain only the thermodynamically stable lowest-free-energy form at any given value [32]. Temperature variations may change the rank order of the thermodynamic stability reflecting the changes in the free energies of the polymorphs. Such a change in terms of solubilities is shown in Fig. 7. The change in rank order is characterized by a transition temperature Tc. From these considerations it is clear that the thermodynamic stability of the polymorphs must be taken into account in studies on crystallization of polymorphs [32]. Changes in the initial pH values have an impact on the ionic strength of the solution, which is related to supersaturation. A higher pH leads to a higher concentration of carbonate ions and a higher supersaturation. When the initial pH value is higher than 7 but is lower than 11, the precipitation of calcium carbonate follows the ACC–vaterite pathway described above [35]. The vaterite abundance and its crystal size increase with higher initial concentrations of Ca2+ and CO2− 3 ions. The change in its dominance with time for the two solutions of different supersaturation values is shown in Fig. 8a. In spite of practically equal ion activity of calcium and carbonate in the initial solutions in (A) and (B), the suspension which contains an excess of Ca2+ (A) gives a higher vaterite abundance. Using a computer program, the rate of crystal growth was determined by numerical differentiation and the growth kinetics was found to be parabolic (Fig. 8b) [15], which is in good agreement with the experimental data obtained elsewhere [33]. Surprisingly, a rather weak dependence of the vaterite growth rate on the ionic strength was found [15].

3. Vaterite characterization and properties 3.1. Structure

Fig. 3. Plots of abundance of crystalline calcium carbonates at the early metastable stage as a function of temperature (plotted from [19]).

Being a metastable polymorph, vaterite rarely exists in nature in the pure form, and large single crystals of vaterite are difficult for obtaining in-vitro. Because of that, it has been a big challenge to resolve the structure of vaterite for almost a century.

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

647

Fig. 4. The effect of supersaturation on the crystallization of polymorphs. The circles indicate different supersaturations (a) (plotted from [32]); solubility of the anhydrous crystalline polymorphs at 1 bar (b) (plotted from [33]).

The most widely accepted fact is that vaterite has a hexagonal crystal symmetry [10,14,20,29,36,37] and P63/mmc space group [16,25,38], with unit pseudo-cell parameters a′ = 4.13 Å and c′ = 8.49 Å. The specific gravity measurements reveal that this cell contains two CaCO3 (Z′ = 2) [25]. Five weak reflections also observed by (X-ray diffraction) XRD initially could not be indexed, and were attributed to the true cell rotated byp 30° ffiffiffi about the c axis from the main one, with lattice parameters a = a0 3 3 = 7.16 Å, c = 2c′ = 16.98 Å, and Z = 12 [25]. The atomic arrangement shown in Fig. 9 is constructed based on the symmetry elements of space group P63/mmc. This model posits 100% occupancy by the calcium and one-third occupancy by the carbonate groups. When the carbon atom was placed in the centre of the prism and the vertical carbonate group was oriented so that each oxygen atom was equidistant from the two nearest calcium atoms, the resultant calcium–oxygen interatomic distances were found to have the expected values [25]. In [38] another structure is suggested. The basic unit cell is essentially in agreement with the previous model but the site symmetry of the carbonate groups is different. It was emphasized that additional spectral features observed in diffraction data (diffuse streaks along the c axis and

satellite reflections) are attributable to stacking faults perpendicular to the c axis, leading to doubling or tripling of the c lattice parameter, as reflected in Fig. 10. The principal debate has arisen on whether the vaterite symmetry is hexagonal or orthorhombic, although recently it was claimed that none of the proposed models is consistent with Raman spectra indicated by the presence of two or more carbonate groups in the asymmetric unit [39]. Based on the spectroscopy data, the possibility of at least three structurally independent carbonate groups in the unit cell of vaterite was proposed. A Raman spectrum of vaterite discussed in [39] is characterized by the presence of at least eight relatively broad bands at frequencies corresponding to the external lattice modes whereas the other bands are split into two or three distinct peaks (Fig. 11). Vaterite peaks in Raman spectra often have high value of full width at half-maximum in comparison with other polymorphs, which implies that the crystal structure of vaterite is not well ordered. The peak broadening is possibly affected as a result of the stacking faults, layer shifts or syntactic intergrowth irregularities, making it difficult to determine the parameters of the crystal structure.

Fig. 5. Schematic depiction of the formation of CaCO3 spherulites and the transformation from amorphous phase to typical calcite [34].

648

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Fig. 6. Plot of the time required to reach the metastable stage (Tm) as a function of temperature (plotted from [19]).

Different variations of the model were proposed, resulting in the unit cell with P6522 or Ama2 space group or modified orthorhombic unit cell. Based on diffraction tomography and transmission electron microscopic data, two structures with very low symmetries (a monoclinic unit cell and a triclinic one) were suggested in [40]. Taking into account all the diffraction data obtained in the study, the lowest symmetries were hypothesized. Nevertheless, the most recent report claims that vaterite should be considered as a combination of two different crystal structures that coexist within a pseudo-single crystal [3]. The structure of vaterite crystal is possibly predominantly hexagonal with at least one other coexisting minor crystallographic structure. The minor atomic structure, existing as nanodomains within the major matrix, is still unknown. The coexistence of two structures of different symmetries largely explains the

amount of contradicting results previously obtained by different research groups all over the world. There are at least three different theoretical models equally well describing the vaterite structure at room temperature. These distinct models, each comprising multiple structures, can explain the disorder of vaterite in terms of different orientations of the carbonate anions, multiple stacking sequences of the carbonate layers, and possible chiral forms. Hence, vaterite is not a single “disordered” structure but should instead be considered as a combination of different forms, and each form can exhibit rapid interchange between multiple structures that possess similar average properties. Besides explaining the existence of several vaterite forms it suggests that perhaps not all samples of vaterite might be the same, while still exhibiting similar spectroscopic properties [41]. The polycrystalline nature of the vaterite particle compared to monocrystalline calcite is evident from diffraction diagrams recorded from areas within the two particle slices displayed in Fig. 12a and b [42]. Random orientation of the crystallites within the vaterite particle should produce continuous circles on the diffraction diagram. The points of increased intensity along the circle reveal the preferential alignment of the crystallites. The fact that these diffraction spots are elongated indicates a certain degree of variation in the crystal orientation. Interestingly, however, the broken ring pattern of electron diffraction obtained from a micrometer-scale area exhibited 6-fold symmetry. For example, the diffraction rings of (110) and (114) were composed of six bright and six dark segments (Fig. 12c). That means that the crystallographic direction of the nanocrystals in the mosaic is not random but roughly arranged in the same orientation. The presence of texture in the vaterite sample supports the concept of spherulitic growth but does not provide sufficient evidence, since a hypothetical ordered aggregation process could give the same diffraction pattern. High resolution TEM image (Fig. 12d) displays the size of the individual crystallites. The diffraction rings in Fig. 12e are more continuous indicating less systematic orientation, emphasizing the variability of the vaterite structure [42]. Fig. 13 reveals an XRD pattern of vaterite power obtained by solvothermal synthesis in the presence of ethylene glycol. The powder XRD exhibits the characteristic reflections of vaterite, which correspond to lattice planes hkl and d-spacings shown in Table 1 [16]. Diffractograms of vaterite spherulites composed of nanocrystalline sub-domains or grains usually reveal relatively broad peaks of low intensity, which still can be analysed by the Scherrer equation relating the grain size and peak width [20,24]. The phase composition can be refined from X-ray diffractograms by Rietveld analysis [14,29,40]. 3.2. Shape and morphology

Fig. 7. Schematic diagram illustrating the solubility relationship between two polymorphic forms as a function of temperature close to the phase transition temperature Tc (plotted from [32]).

The particle morphology may be the most uncertain characteristic because it displays a great deal of variety. The main crystal structure of polycrystalline vaterite is hexagonal with typically a spherical crystal habit like the one shown in Fig. 14a [5,9,13,17,24,43–47]. The spherical form is also called framboid [5] or raspberry [27] (translation of ‘la framboise’ from French). A detailed examination of particle surface showed that spheroids are composed of smaller single crystal subunits (Fig. 14b) arranged with some degree of order as mentioned earlier. The most common interior feature is the presence of grooves radiating from the centre of the particle as radial fibre-like (or channellike) structures (Fig. 14c). Fracture cross-section images display nanograins developed into oriented rods (Fig. 14d). The deviation angle of each main bundle of the oriented rods was roughly estimated to be about 60° (Fig. 14e). A so-called “sheaf of wheat” inner structure of spherulites was observed in [5,48]. One can imagine this structure as a bundle of fibres tied together at the centre, so that the ends fan out. While the number of growing fibres increases their ends close off to form a sphere. The particle growth scenario called “sphere-to-dumbbell-to-sphere” (Fig. 14f) is currently one of the most explored [21,24,29,49].

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

649

Fig. 8. Plots of vaterite abundance as a function of time in metastable stage as 25 °C with initial concentrations of calcium and carbonate (a). Initial concentrations: (A) 0.11 M CaCl2–0.10 M Na2CO3 and (B) 0.10 M CaCl2–0.11 M Na2CO3 (plotted from [19]). Plots of the square root of the growth rate as a function of the relative supersaturations and various ionic strengths (b) [15].

Besides the typical spheroidal structure, in vitro precipitation of vaterite often results in a variety of complex shapes: fried-egg shape, different kinds of layered flower-like (Fig. 15a, b) or rosette-shaped structures (Fig. 15c) united with 6-fold symmetry [24,31,36,50,51]. Fig. 15d, e, and f represents a typical SEM image and a suggested a formation scheme for such hexagonal-shaped vaterite composed of small hexagonal units. Other reported shapes of vaterite [16,35,50,52] are plates and lenses (Fig. 16a and b). Plate morphology is probably the characteristic for the intermediate stage of cauliflower-like particle growth, since other petals growing on plane regions can be seen (Fig. 16b). However, the development mechanisms, resulting textures, and common features of all different shapes are yet to be explored. Importantly, in minor cases, calcite could also have a spherical habit [42], so the particle analysis must not rely solely on SEM images, but be supplemented with the methods discovering more exhaustive information about the phase, e.g., XRD.

3.3. Porosity High specific surface area and porosity of vaterite particles are of particular importance for their practical applications. Brunauer– Emmett–Teller (BET) analysis reveals the specific surface area of the vaterite framboids to be 3.2–8.8 m2 g−1 for different precipitation conditions [5,43,53–55]. Vaterite particles with the highest surface area

24.72 m2 g−1 were achieved via coprecipitation with inulin [56]. Besides, the pore size distribution displayed an average pore size of 20– 60 nm for the particles with a medium diameter of 4–6 μm [43]. Theoretical equation evidently indicates that specific surface area is subject to exponential decay with increasing particle size [5]. 3.4. Absorption spectrum Fourier transformation infrared spectroscopy (FTIR) is a very useful technique to identify the polymorph composition of CaCO3 particles [21,50,57]. The absorption bands of the different crystallographic varieties of CaCO3 are listed in Table 2. Pure vaterite exhibits the characteristic vibrational bands at 1480, 1070, 1087, 877, 848 and 745 cm−1, where the last three of the listed bands are the most typical and informative [17,18,35,53,58]. The selected FTIR spectrum for vaterite samples precipitated in mono-ethylene glycol solution at 40 °C (Fig. 17) shows representative bands at 1088, 874 and 744 cm−1 attributing to the deformation modes of CO3 in the vaterite polymorph [14]. The shifts of peak positions in FTIR spectra indicate interactions between calcium ions and chemical groups of additional molecules in the reaction medium (additives or impurities) [10,14,16,18]. Shift magnitude directly corresponds to the strength of such interactions. 3.5. Chemical and physical properties Owing to the mass density (2.54 g·cm−3), solid vaterite is used in regenerative medicine [5] for doping of implant scaffolds. Besides, calcium carbonate is quite inert and biocompatible. CaCO3 structure has good stability at neutral and alkaline pH but begins to dissolve at

Fig. 9. Vertical projection of vaterite showing orientation of carbonate group relative to calcium atoms [25].

Fig. 10. Structure of the vaterite unit cell [38].

650

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Fig. 11. Raman spectra of vaterite [39].

slightly acid conditions opening an opportunity of using pH to trigger disassembly in practical applications [44]. The solubility of calcium carbonate is different for different polymorphs and was found to be lg Ksp = −7.913 for vaterite at 25 °C [23,35,55]. Moreover, the solubility of vaterite particles is in direct relationship with the concentration of CO2 gas in water medium [59]. The increase of CO2 content leads to the high CO23 − concentration in the solution, which, as discussed in [8], increases the fraction of vaterite. 4. Facilitating vaterite formation The morphology and polymorph composition of CaCO3 is very sensitive to synthesis conditions. Many efforts have been made to favour the growth of vaterite over the other calcium carbonate polymorphs. Various experimental conditions are supposed to promote synthesis of this metastable phase. Among those, the use of highly saturated salt solutions, alkaline pH, and temperature control induces the vaterite formation with high yield of stable particles [18,23,35,49,60]. The sources of calcium and carbonate ions have significant effect on the morphology and phase of CaCO3. CaCl2 salt appears to be the most

Fig. 13. X-ray diffraction pattern of vaterite [10].

popular compound [9,17–19,30,43,61–64]. Ca(NO3)2 is less frequently used [22,42,54]. The most common source of carbonate ions is sodium carbonate Na2CO3 [19,43,62,42,22,30], other sources are sodium bicarbonate NaHCO3 [54,61,63], ammonium carbonate (NH4)2CO3 [9,4,17, 64] and ammonium bicarbonate NH4HCO3 [18]. Facilitating factors include the presence of certain additives in the aqueous medium, which are thought to influence the crystallization of vaterite polycrystals by several different mechanisms. Generally, interaction between added molecules and calcium and carbonate ions individually lowers the concentration of freely available ions in bulk medium and decreases the actual thermodynamic driving force for nucleation. Lower nucleation rate delays the formation of more stable polymorphs of aragonite and calcite promoting the vaterite fraction. Additives can also influence the kinetics of crystal growth. The additive molecules may have greater affinity with certain faces of a particular

Fig. 12. Electron diffraction patterns of vaterite with a certain degree of variation in crystal orientation (a) and calcite (b) [42]; electron diffraction pattern of vaterite with nanocrystals arranged in the same orientation (c) [24]; a high-resolution image of primary crystals of vaterite (d); electron diffraction diagram of vaterite with crystallites in random orientation (e) [42].

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658 Table 1 XRD data (hkl indices and corresponding d-spacings) for vaterite [16]. h

k

l

dobs/Å

0 1 1 1 2 2 1 2 0 3 3 1 2 2 2

0 1 1 1 1 0 1 1 0 0 0 1 2 0 2

4 0 2 4 1 5 6 3 8 0 4 8 0 8 4

4.254 3.591 3.307 2.741 2.327 2.287 2.223 2.167 2.122 2.070 1.860 1.826 1.792 1.752 1.650

polymorph and will adsorb strongly onto these faces, delaying the nucleation or retarding the growth of the affected polymorphs to the advantage of others. Besides, it is mentioned that when the basicity of the basic additive increases (e.g. urea, sodium hydroxide), the sizes of CaCO3 structures decrease [4,10]. Vaterite precipitation is promoted by inorganic additives (for instance ammonia, ammonium ions, nitric acid) [4,12,31,50,65], certain organic substances such as amino acids [53,63,66], protein molecules (e.g., bovine serum albumin, ovalbumin, gelatin, casein, polyglycine, fibrin, pelovaterin) [6,11,25,53,57,61–63,67–69], and sucrose [61].

651

Other frequently used compounds are poly(styrenesulfonate) [22,24], polyacrylic acid [23,27,64], polyvinylpyrrolidone [23,34], poly(vinyl alcohol) [22,23], polycarboxylic acid [30], carboxymethyl inulin [56]), copolymers [58,60], including double-hydrophilic block copolymers (DHBCs) [13,21,49,52], dendrimers [17,70], and calixarene [36]. Besides, DHBCs and dendrimers were mixed with surfactants [52,70]. Moreover, ionic liquid surfactant can be utilized as an effective polymorph control agent on its own [16,35]. Different kinds of alcohols are also referred as the vaterite promoters and stabilizers [4,14,21,29,37,42,59,71].

4.1. Nitrogen containing compounds A number of amino acids (lysine, glycine, alanine, glutamic acid, leucine) were found to stabilize the vaterite polymorph [53,66]. It is assumed that calcium ions are attracted by strong electric field caused by shifting the negative charge of the C_O bond towards the oxygen atom. The electrostatic interactions temporarily fixed Ca2 + ions near C_O groups that along with the diffused carbonate ions towards the fixed Ca2 + initiate the vaterite critical nucleus formation. Onwards, the amino acids interact with Ca2 + ions of the crystal surface with their side terminal carboxyl groups or through hydrogen bonding. Crystallization in the presence of nitric acid, organic amines, and tetrasodium etidronate resulted in vaterite nucleation as well [7,65]. Biotic experiments [12] suggest that tight binding between amide groups and vaterite surface via NH\O hydrogen bonds controls CaCO 3 polymorph selection providing long-term stabilization of vaterite.

Fig. 14. SEM-images of calcium carbonate vaterite crystals: top view (a), surface (b) [47], interior (c) [43], cross-section (d) and detailed fibre-like structure (e) [24], and possible particle growth scenario (f) [24].

652

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Fig. 15. Vaterite particles of different shapes. Flower-like vaterite particle (a), a magnified SEM image of the particle surface (b) [31], rosette-shaped vaterite (c) [36], hexagonal-shaped vaterite and particle magnified surface (d) [24], and possible growth mechanism (e) [31].

4.2. Proteins Proteins like bovine serum albumin (BSA) have been successfully used to manipulate the polymorphic phases [61,67] and crystal morphology of calcium carbonate and have shown strong influence on the oriented crystallization and growth. Moreover, the reduction of crystal size by albumin is also reported [11,63]. During the formation of vaterite spheres, the nucleation and growth of the crystals might be affected by the protein through electrostatic matching, and structural and interfacial molecular recognition. The role of BSA in the formation of vaterite attributes to a big variety of functional groups: C_O, HO\, N\H, C\N, etc. [11,61,62,67]. In [11] it was demonstrated that ovalbumin from chicken egg white displayed a distinguished stabilizing effect on the vaterite phase by ovalbumin adsorption onto the unstable surface of the crystal. As an acidic protein, ovalbumin could capture Ca2 + through carboxylates at the periphery of the protein, thereby leading to a local enrichment of calcium ions. Upon introduction of CO2− and 3 diffusion into the solution, their distributions would be enriched by Ca2+ ions around the protein. According to the Ostwald rule, the metastable crystalline form may tend to precipitate under a higher local supersaturation, resulting in the production of vaterite crystals around the protein molecules. Furthermore, ovalbumin will adsorb onto the

surface of vaterite crystals upon their formation, thereby retarding its transformation into more stable crystalline forms. The special peptide–pelovaterin, extracted from eggshells of a softshelled turtle, was synthesized specifically to induce the nucleation and stabilization of the vaterite phase in solution [69]. It is a glycinerich peptide with 42 amino acid residues and three disulphide bonds. Compared with proteins containing no phosphonate groups, phosphoproteins (ovalbumin, casein) might have specific and prominent influences on mediating the mineralization process [57]. It has been found that organophosphorus compounds adsorb to ionic crystals much more strongly than other additives. They preferentially interact with kinks on the crystal nucleus surface [57] and adsorb onto the sites of active growth [54] and thus efficiently inhibit the crystal growth and lead to the generation of the least stable vaterite. The effect of phosphonates on the crystal habit must be related to the affinity of a compound to Ca2 +, which influence the crystallization rate and change the morphology of crystals [22,54]. Besides proteins, some other compounds with phosphonate groups are also known to facilitate the vaterite formation [7,13]. In short, the effects of proteins on the vaterite stabilization and growth are attributed to the enriching of calcium ions around their molecules due to new bond formation.

Fig. 16. SEM-images of the vaterite particles of lens (a) [50] and plate (b) [52] shape.

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658 Table 2 Assignment of the IR absorption bands of the three polymorphs [16]. IR absorption band

Vaterite Aragonite Calcite

ν1, cm−1

ν2, cm−1

ν3, cm−1

1087 1080 1080

877 866 879

745 706 706

4.3. Polymers It can be claimed that the growth of crystalline CaCO3 is a surfacecontrolled process, which means that the adsorption of water-soluble polymers should have strong influence on both velocity and habit of the crystal growth, changing their morphology and structure. It was found that the presence of polyvinylpyrrolidone (PVP) leads to spherical vaterite particles [23] (but has a very slight effect) and alters the surface morphology of vaterite at high PVP concentrations [34]. The PVP easily absorbs on the surface of the initially formed spheres of amorphous CaCO3, and consequently, the loops and trains of the absorbed polymer molecules make the cauliflower-shaped spherulites more incompact and rough [27,34]. This could be easily understood by referring to the hypothesis of the formation mechanism illustrated in Fig. 18 [49]. Polyacrylic acid (PAA) is also known to control crystal size, quality, and shape by increasing the induction time of vaterite [23]. Polymer inclusion in vaterite modifies the parameters of unit-cell in the respective phases [27]. Taken in a low concentration, PAA completely dissociates in water, and liberates protons into bulk solution: PAA ↔ PAA(COO−) + H+. In the resulting acidic conditions, CaCl2 solubility is increased, giving rise to more Ca 2 + and thus Ca 2 +–polyelectrolyte complexes as a result of chemical reaction: PAA(COO −) + Ca 2 + ↔ PAA(COO)Ca + . The PAA(COO)Ca + complexes are formed rapidly, and it seems reasonable to hypothesize that this reaction takes place wherever highly energetic sites are present. It is well known that vaterite crystals predominately grow in the direction of their c-axes upon crystallization from supersaturated solution, and highly energetic sites in vaterite occur preferentially on faces parallel to the c-axes, i.e. where oxygen atoms from carbonate groups are most located. Resultantly, the complex adsorbs preferentially on these faces that block further growth to another axes and prevent vaterite transformation [27]. Pores of the spherical vaterite particles are filled by further vaterite growing under PAA complexes, giving rise to the raspberry shapes by aggregation of several spheres

653

(or to further development of each initial conglomerate under PAA influence). The surface morphology (smooth or rough) and crystal interior (radiating features) depend on the moment the polymer is interfering with the crystallization process and polyelectrolyte chain length (Fig. 19). Ca2+-activity measurements show that polymers are partially incorporated into the forming crystals [30]. At that, the polymer contaminated CaCO3 particles exhibit strong resistance towards aggregation into flocs and are stable to recrystallization process in water attributed to the formation of a polymer shell [27,30]. Particle stabilization can be of permanent or temporary nature depending on the amount of polymer in the system. Temporary effect is achieved when the amount of polymer is insufficient to cover the surface of all formed nanoparticles. Uncoated nanoparticles will then undergo dissolution and recrystallization. Sufficient amount of polymer enables permanent stabilizing effect [30]. The effect of polymers on the crystal habit is shown to be related with the affinity between polymer and Ca2+ and even distribution of polymer molecules over the volume of CaCO3 crystals [22]. This mechanism is probably attributed to a variety of polymers. Among the polymers employed for vaterite promotion, the PAA and polystyrene sulfonate (PSS) are obviously the most effective in the retention of spherical shape [22,24,64]. Anionic groups or lone pair electrons in polymers are supposed to play a role in arranging calcium ions and regulating the crystal form. Besides, the clusters can be formed by the addition of multivalent ions (like Ca2 +) to polyacrylic acid [72–74]. At a certain point, the clusters become large enough to precipitate out, which is known as the “gel point” [72]. Therefore, the precipitation obtained from the supersaturated solution in the presence of PAA may consist of both vaterite and calcium polyacrylate clusters and the sample composition should be examined particularly carefully. As for phosphorus containing polymers, sodium polyphosphate has been successfully used [7]. Moreover, phosphonate groups in copolymers strongly promote vaterite formation and their influence becomes significant with increasing the number of phosphonate groups [13]. 4.4. Double-hydrophilic block copolymers Double-hydrophilic block copolymers (DHBCs) consist of a hydrophilic poly(ethylene glycol) (PEG) block and a second hydrophilic moiety which strongly binds alkaline earth ions effectively inhibiting the CaCO3 precipitation [49]. This was explained by the block copolymer character and the related “sharing of responsibilities”: the COOHfunctionalized block interacts with nanocrystals or nuclei, whereas another block keeps the microcrystals in solution by steric stabilization without interaction with the dissolved ions. Since both tasks do not interfere with each other, both blocks can be independently optimized with respect to polymorph composition, size, functionality and structure [13,49]. And it is clear that an optimal functional block length should exist [13,21]. Copolymers with poly(ethylenimine)-poly(acetic acid) (PEG-PEIPA) functional block are shown as very efficient templates to promote pure vaterite crystals of smaller size when used in moderate concentration [13,21]. 4.5. Dendrimers

Fig. 17. FT-IR spectra of vaterite [14].

Owing to spherical three-dimensional morphology and highlyfunctionalized terminal surface dendrimers are successfully used as a central initiating core for vaterite particle formation [17,70]. The commonly utilized poly(amido amine) (PAMAM) has enough amine branches (nitrogen moieties) serving as the complexation sites to ions [17]. Another dendrimer, poly(propylene imine), combined with a cationic surfactant was proposed as a template to attract carbonate ions preferentially forming a stabilized surface ready to absorb more ions for subsequent vaterite formation [70]. Elsewhere [17] vaterite surface

654

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Fig. 18. Proposed mechanism of vaterite formation: (a) The polymer-stabilized amorphous nanoparticles; (b) formation of spherical vaterite precursors; (c) aggregation of the vaterite nanoparticles [49].

is stabilized by the carboxylate-terminated dendrimer with a long lasting effect: incubation in water for 1 week did not change the crystal morphology. Increasing the concentration of additive and the generation number of the dendrimer, allows to reduce the size of vaterite particles from 5.8 down to 1.5 μm [17]. These results indicate a higher complexation ability of a higher generation of the PAMAM dendrimer compared to that of a lower generation, since the particle size depends on the degree of the dendrimer adsorption on primary nanoparticles. 4.6. Alcohols Phase-pure vaterite was found to be promoted by OH-groups of polyols [10,37,42,71]. Strong electric field caused by OH-groups induces attraction to the nuclei changing the surface energy of vaterite and making it more thermodynamically stable than the aragonite and calcite modifications [10]. No phase-pure vaterite was achieved by adding alcohols with only one OH-group [10,29] except for ethanolamine which favours the vaterite habit by NH2 functional group [65]. Alcohols with two or three hydroxyl groups (e.g., ethylene glycol (EG) and glycerol) offer an enhanced solution density and reduced solubility of the carbonate [37,42,71]. Since vaterite has relatively high solubility in

water, non-aqueous solvents were suggested to benefit its precipitation [14]. A decrease of the activation energy of nucleation by the interfacial molecular recognition was pointed out as another factor facilitating vaterite precipitation [6,37,42]. Similar to polymers, polyols prolong the transformation time of metastable polymorphs (perform the socalled kinetic stabilization) presumably by delaying the growth rate of the more stable polymorphs [37] and thus hinder recrystallization to more stable phase. The presence of a co-solvent also affects supersaturation, because of changes in the ion activity coefficients and solubility of the calcium and carbonate salts [14,37]. According to the classical nucleation theory, the smaller crystals are the result of higher nucleation rates, provided that the same mass is precipitated [37,59]. Admixture ethylene glycol and glycerol to salt solutions increases nucleation rates resulting in smaller vaterite at a range of temperatures [37]. Additionally, high local viscosity of the reaction medium containing glycerol or other compounds, such as sucrose, ethanolamine precursors, gelatine or alginate hydrogels can significantly limit the rate of diffusion for Ca2+ ions and effectively slow down the crystallization [7,21,25,61,65,75]. Summarising this paragraph, the factor facilitating stability of the vaterite phase and promoting smaller particle size is a high amount of functional groups in the system achieved by, e.g., high concentration

Fig. 19. Schematic depiction of the CaCO3 spherulites formation with addition of a polymer [64].

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

of additives, using polymers of high molecular weight, or dendrimers with a higher generation number [10,17,22,23,34,53,54,56,64].

4.7. Microorganisms Some bacteria are capable to produce the CO2 and NH3 gases and − transform the NH3 to the NH+ 4 and OH . Since supersaturation is higher in more alkaline medium, the condition favourable for vaterite precipitation is set. As a result, the vaterite formation occurs in the microenvironment around the cells, and directly onto their surface. Bacteria cell walls contain a number of surface functional groups, such as carboxyl, hydroxyl and phosphate sites known to promote vaterite crystallization and stabilization. The results of vaterite precipitation in the presence of different types of bacteria (common soil bacterium [12] and actinomycete [76]) suggest that bacterially mediated vaterite precipitation is not strain-specific.

5 . Application of vaterite 5.1. Personal care Biological inertness, low toxicity and unique mechanical, physical and chemical properties of precipitated vaterite microparticles benefit to a broad range of personal care products. Vaterite crystals are commonly added to industrial personal care products with the purpose to improve rheology, physical robustness and visual appearance. Vaterite particles can act as abrasives, absorbents, anticaking agents, buffers, fillers, colorants, and emulsion stabilizers [65,77,78] Besides, the use of CaCO3 material is safe for environment and extremely cost efficient. A strong demand for spherical vaterites persists in the field of oral care. Among the other CaCO3 polymorphs, vaterite demonstrates excellent cleaning properties without being excessively abrasive. Vaterite microparticles of a certain size (0.2–4 μm) are reported to improve cleaning and abrasive characteristics of dentifrice formulators, teeth whitening products and mouthwashes [7]. Moreover, low cost of CaCO3 particles makes them a perfect substitute for silica and dicalcium phosphate particles. Other personal care products employing calcium carbonate particles as an abrasive include facial cleansing soaps, exfoliating formulations, acne preventing wipes, bath soaps, bath wash, makeup removers, baby wipes, diapers, powdered bleaches and all-purpose cleaners [77]. Abrasive properties of vaterite particles are gentle enough to be successfully utilized in paint removals specially designed to clean delicate surfaces of lightweight metals and plastics. Skin care, makeup and cosmetic products enjoy the properties of CaCO3 particles to eliminate unwanted shine and create whiteness. Besides, as the vaterite particles of a certain size can scatter UV light, they may serve in fabrication of sunscreens, face powders, blushes and foundations [77]. Absorbent property of calcium carbonate is used in eyeshadows, blushes, concealers, foundations, face powders, sunscreens, sun-tan lotions, self-tanning compositions, bronzers, baby powders, diapers, deodorants and antiperspirants. Anticaking characteristics of CaCO3 used a range of products from face powder and eyeshadow to laundry detergent, bathroom cleaners and powdered bleach [77]. Vaterite is also known to maintain pH in aqueous medium. Buffering properties of vaterite are often employed in non-ingestible formulations, such as lip gloss, nail polish, makeup removal, different creams and lotions, teeth whitening agents and all-purpose cleaners. Moreover, there is a number of food products where vaterite serves as a pH buffer, i.e. salad dressings, water-based flavored drinks (e.g., energy drinks, sports drinks, electrolyte drinks), canned fruits, vegetables and meats. Some emulsion based food products (e.g., salad dressings) also enjoy a phase stabilizing property of vaterite particles [77].

655

5.2. Biomedical applications Vaterite and other calcium-based inorganic nanostructured materials are extensively applied in regenerative medicine and tissue engineering as bone cements and substitute materials, dental implants, and scaffolds. [4,79–82]. Better mechanical strength compared to polymer materials, makes vaterite doped implants promising for strengthening the bone and dental tissues. Vaterite degrades in vivo at sites with acidic pH, thus replenishing calcium in a living organism and promoting tissue regeneration [4,79,81]. It is well known that tooth and bone are the naturally organic/inorganic composites having calcium phosphate, hydroxyapatite, calcium silicate, and calcium carbonate in the structure. Hydroxyapatite and calcium phosphate are proved to be the most similar materials to bone mineral that predetermined their extensive use in clinical bone graft procedures. Importantly, their simplest synthesis method is based on the replacement of carbonate group to phosphate group in vaterite [4]. The characteristic features of new bone formation was found to be identical in implants of either calcium carbonate or hydroxyapatite — percentage of the pore space occupied by bone at 4 weeks after implantation was the same, and the marrow cells were detected in pore areas of both implants [79]. But in contrast to hydroxyapatite, porous CaCO3 implants with or without marrow cells showed some degradation — the material has a potential to completely degrade. Previous studies have shown that porous CaCO3 completely degrades after 3 months when placed in a bone forming a defect [79]. The carbonate surface can be modified with hydroxyapatite to control the rate of biodegradation. Vaterite-based materials with pore microstructure and high surface area can be used as preservative containers for growth factors [80]. Being added to the scaffolds, they will promote proliferation and differentiation of cells towards osteoblasts. Moreover, vaterite being in contact with body fluid dissolves immediately, supplying calcium ions, while part of it re-crystallizes as the most stable calcite. Simultaneously released carbonate ions neutralize pH at the inflamed site of implantation [80]. Highly porous vaterite particles have been extensively used in pharmaceutical applications as encapsulating carriers for various drugs [9, 44,62,83]. The structure and surface morphology open up an opportunity to absorb a large range of biomolecules. Spherical CaCO3 with an enzyme immobilized into pores was demonstrated as a platform for the design of biosensors [47]. High porosity of the vaterite beads is a key feature that leads to good adsorption ability to silver and gold nanoparticles. Vaterite surface enhanced with nanoparticles is attractive for developing biomarker sensing at concentrations corresponding to healthy and diseased individuals (e.g. for glycose detection) [84]. Based on their high birefringence vaterite particles can be used in the fields of microrheology, microfluidics and micromanipulation at the single molecule level [20]. Triggered by the early studies of Volodkin et al. [43,85–87], the employment of vaterite microparticles has promoted a significant breakthrough in the area of encapsulation and delivery of drugs by Layer-by-Layer (LbL) assembled capsules. Vaterite is found to co-precipitate a number of therapeutics, such as nucleic acids, enzymes, antibodies and proteins. Subsequent coating with polymer multilayers and CaCO3 dissolution result in LbL capsules loaded with the co-precipitated compound [43,89]. Moreover, it was observed that CaCO3-assisted encapsulation results in a higher loading efficiency for some type of compounds [90,91]. Promising attempts of in vitro and in vivo delivery by 2–4 μm microcapsules templated on vaterite particles for disease treatment and vaccination have been shown [89,92]. An important feature of LbL capsules made of synthetic and natural polyelectrolytes in different combinations is their tunable biodegradability [93]. Recent studies have also revealed that capsule shape is a crucial parameter influencing the cellular uptake. Elongated objects can be effectively and quickly internalized intercellularly compared with other configurations. Thus fabrication of anisotropic

656

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

Fig. 20. CLSM images of L929 cells incubated with FITC-BSA-loaded (Dex/PAr)3 microcapsules: (a) Cross-section fluorescence image with z-axis fluorescence projection at the cross-plane displayed (windows at the bottom and on the right), scale-bar: 20 μm. (b) Overlap of fluorescence mode and bright-field mode, scale-bar: 20 μm. (c) 3D fluorescence image from the top view, frame length, and width: 210 μm; height: 13 μm [88].

particles and polyelectrolyte multilayer capsules templated on them is of a special interest [94]. Although such capsules still can enter the living cells and deliver the therapeutics (Fig. 20) [92,95], we believe that the effect would be much stronger if the size of their CaCO3 templates was reduced. Thus, new ways to achieve smaller vaterite particles co-precipitating biologically active molecules are to be discovered.

6. Conclusion Owing to biodegradability and unique physical and chemical properties, vaterite polymorph of calcium carbonate is extensively used in biomedicine and added to a wide range of personal care products. The most cost efficient way to produce the CaCO3 microparticles is spontaneous precipitation by mixing of two concentrated solutions of calcium and carbonate salts. Being a metastable polymorph, vaterite may transform to either calcite or aragonite in this process. Here we have reviewed the most accepted suggestions on the mechanism of calcium carbonate crystal growth focusing on various factors promoting the vaterite polymorph. It has been proven that high supersaturation, ambient temperature, and alkaline pH facilitate the formation of vaterite over more stable modifications. Moreover, various inorganic and organic additives particularly those bearing carboxylic, phosphonate, sulfonate, hydroxyl, carboxylate and amino groups are responsible for the vaterite morphology. The process is tunable: changing the concentration of additive, molecular weight and the amount of functional groups allows controlling the growth rate, crystal habit and stability, particle size and surface morphology. Thus, synthesis conditions can be configured to allow stable vaterite particles which fulfil the size requirement in each particular application. Among a number of application areas of the vaterite polymorph, polymeric Layer-by-Layer drug delivery may be the most novel and fast progressing one. Vaterite microparticles have already enabled achieving high loading efficiency for a range of therapeutics and analytes. Reduction of size of the co-precipitated vaterite polycrystals is envisioned to increase the rate of intracellular uptake for the corresponding capsules.

Acknowledgement Daria Trushina thanks A*Star Graduate Academy (Singapore) and Russian Foundation for Basic Research (Grant No. 14-03-31889) for support.

References [1] J.D.C. McConnell, Vaterite from Ballycraigy, Larne, Northern Ireland, Mineral. Mag. 32 (250) (1960) 534–544. [2] M. Sato, S. Matsuda, Structure of vaterite and infrared spectra, Z. Krist. 129 (1969) 405–410. [3] R. Demichelis, P. Raiteri, J.D. Gale, R. Dovesi, A new structural model for disorder in vaterite from first-principles calculations, Cryst. Eng. Comm. 14 (2012) 44–47. [4] M.-G. Ma, R.-C. Sun, Biomineralization and Biomimetic Synthesis of Biomineral and Nanomaterials, in: A. George (Ed.), Advances in Biomimetics, InTech, Croatia, 2011, (Chapter 2). [5] G. Nehrke, P. van Cappellen, C.H. van der Weijden, Framboidal vaterite aggregates and their transformation into calcite: a morphological study, J. Cryst. Growth 287 (2006) 528–530. [6] D. Bassett, J. Barralet, Control of Calcium Carbonate Crystallization by a Serum Protein, the OCCAM–Fields–MITACS Biomedical Problem Solving Workshop, 2009. [7] S.-T. Liu, H. J. M. Corp, Stabilized vaterite, US Patent, Jun 25, 2004. [8] Y.S. Han, G. Hadiko, M. Fuji, M. Takahashi, Effect of flow rate and CO2 content on the phase and morphology of CaCO3 prepared by bubbling method, J. Cryst. Growth 276 (3-4) (2005) 541–548. [9] M. Fujiwara, K. Shiokawa, M. Araki, N. Ashitaka, K. Morigaki, T. Kubota, Y. Nakahara, Encapsulation of proteins into CaCO3 by phase transition from vaterite to calcite, Cryst. Growth Des. 10 (9) (2010) 4030–4037. [10] Q. Li, Y. Ding, F. Li, B. Xie, Y. Qian, Solvothermal growth of vaterite in the presence of ethylene glycol, 1,2-propandiol and glycerine, J. Cryst. Growth 236 (2002) 357–362. [11] X. Wang, C. Wu, K. Tao, K. Zhao, J. Wang, H. Xu, D. Xia, H. Shan, J.R. Lu, Influence of ovalbumin on CaCO3 precipitation during in vitro biomineralization, J. Phys. Chem. B 114 (2010) 5301–5308. [12] C. Rodriguez-Navarro, C. Jimenez-Lopez, A. Rodriguez-Navarro, M. Teresa GonzalezMunoz, M. Rodriguez-Gallego, Bacterially mediated mineralization of vaterite, Geochim. Cosmochim. Acta 71 (2007) 1197–1213. [13] H. Cölfen, M. Antonietti, Crystal design of calcium carbonate microparticles using double-hydrophilic block copolymers, Langmuir 14 (1998) 582–589. [14] C.D. Mateescu, C. Sarbu, R. Isopescu, O. Dumitrescu, D. Ghica, Sonocrystallization of calcium carbonate metastable polymorphs in alcoholic solutions as reaction media, 18th International Symposium on Industrial Crystallization, 2011, p. 4. [15] L. Brecevic, D. Kralj, On calcium carbonates: from fundamental research to application, Croat. Chem. Acta 80 (2007) 467–484. [16] L. Dupont, F. Portemer, M. Figlarz, Synthesis and study of a well crystallized CaCO3 vaterite showing a new habitus, J. Mater. Chem. 7 (1997) 797–800. [17] K. Naka, Y. Tanaka, Y. Chujo, Effect of anionic starburst dendrimers on the crystallization of CaCO3 in aqueous solution: size control of spherical vaterite particles, Langmuir 18 (2002) 3655–3658. [18] J. Chen, L. Xiang, Controllable synthesis of calcium carbonate polymorphs at different temperatures, Powder Technol. 189 (2009) 64–69. [19] T. Ogino, T. Suzuki, K. Sawada, The formation and transformation mechanism of calcium carbonate in water, Geochim. Cosmochim. Acta 51 (1987) 2757. [20] S.J. Parkin, R. Vogel, M. Persson, M. Funk, V.L.Y. Loke, T.A. Nieminen, N.R. Heckenberg, H. Rubinsztein-Dunlop, Highly birefringent vaterite microspheres: production, characterization and applications for optical micromanipulation, Opt. Express 17 (24) (2009) 21944. [21] H. Cölfen, L. Qi, A systematic examination of the morphogenesis of calcium carbonate inthe presence of a double-hydrophilic block copolymer, Chem. Eur. J. 7 (1) (2001) 106–116. [22] H. Kawaguchi, H. Hirail, K. Sakai, S. Sera, T. Nakajima, Y. Ebisawa, K. Koyama, Crystallization of inorganic compounds in polymer solutions. Part I: control of shape and form of calcium carbonate, Colloid Polym. Sci. 270 (1992) 1176–1181.

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658 [23] E. Altay, Effect of reaction conditions and organic additives on the morphologies of synthetic calcium carbonates, Izmir Institute of Technology in Partial Fulfillment2006. [24] H. Imai, N. Tochimoto, Y. Nishino, Y. Takezawa, Y. Oaki, Oriented nanocrystal mosaic in monodispersed CaCO3 microspheres with functional organic molecules, Cryst. Growth Des. 12 (2012) 876–882. [25] S.R. Kamhi, On the structure of vaterite, CaCO3, Acta Crystallogr. 16 (1963) 770–772. [26] J.-P. Andreassen, M.J. Hounslow, Growth and aggregation of vaterite in seededbatch experiments, published online in Wiley, InterScience 50 (11) (2004) 2772–2782. [27] S. Ouhenia, D. Chateigner, M.A. Belkhir, E. Guilmeau, C. Krauss, Synthesis of calcium carbonate polymorphs in the presence of polyacrylic acid, J. Cryst. Growth 310 (2008) 2832–2841. [28] J.-P. Andreassen, Formation mechanism and morphology in precipitation of vaterite — nano-aggregation or crystal growth? J. Cryst. Growth 274 (2005) 256–264. [29] K.K. Sand, J.D. Rodriguez-Blanco, E. Makovicky, L.G. Benning, S.L.S. Stipp, Crystallization of CaCO3 in Water–Alcohol Mixtures: Spherulitic Growth, Polymorph Stabilization, and Morphology Change, Cryst. Growth Des. 12 (2012) 842–853. [30] J. Rieger, T. Frechen, G. Cox, W. Heckmann, C. Schmidt, J. Thieme, Precursor structures in the crystallization/precipitation processes of CaCO3 and control of particle formation by polyelectrolytes, The Royal Society of Chemistry, Faraday Discuss. 136 (2007) 265–277. [31] Q. Hu, J. Zhang, H. Teng, U. Becker, Growth process and crystallographic properties of ammonia-induced vaterite, Am. Mineral. 97 (2012) 1437–1445. [32] S. Khoshkhoo, J. Anwar, Crystallization of polymorphs: the effect of solvent, J. Phys. D: Appl. Phys. 26 (1993) B90–B93. [33] R. Beck, J.-P. Andreassen, The onset of spherulitic growth in crystallization of calcium carbonate, J. Cryst. Growth 312 (2010) 2226–2238. [34] H. Wei, Q. Shen, Y. Zhao, D.-J. Wang, D.-F. Xu, Influence of polyvinylpyrrolidone on the precipitation of calcium carbonate and on the transformation of vaterite to calcite, J. Cryst. Growth 250 (2003) 516–524. [35] Y. Zhao, W. Du, L. Sun, L. Yu, J. Jiao, R. Wang, Facile synthesis of calcium carbonate with an absolutely pure crystal form using 1-butyl-3-methylimidazolium dodecyl sulfate as the modifier, Colloid Polym. Sci. 291 (2013) 2191–2202. [36] M. Fricke, D. Volkmer, C.E. Krill, M. Kellermann, A. Hirsch, Vaterite polymorph switching controlled by surface charge density of an amphiphilic dendron-calix[4] arene, Cryst. Growth Des. 6 (2006) 1120–1123. [37] E.M. Flaten, M. Seiersten, J.-P. Andreassen, Polymorphism and morphology of calcium carbonate precipitated in mixed solvents of ethylene glycol and water, J. Cryst. Growth 311 (2009) 3533–3538. [38] H.J. Meyer, Struktur und fehlordnung des vaterits, Z. Kristallogr. 128 (1969) 183–212. [39] U. Wehrmeister, A.L. Soldati, D.E. Jacob, T. Hager, W. Hofmeister, Raman spectroscopy of synthetic, geological and biological vaterite: a Raman spectroscopic study, J. Raman Spectrosc. 41 (2010) 193–201. [40] E. Mugnaioli, I. Andrusenko, T. Schüler, N. Loges, R.E. Dinnebier, M. Panthöfer, W. Tremel, U. Kolb, Ab initio structure determination of vaterite by automated electron diffraction, Angew. Chem. Int. Ed. 51 (2012) 1–7. [41] R. Demichelis, P. Raiteri, J. Gale, R. Dovesi, The multiple structures of vaterite, Cryst. Growth Des. 13 (6) (2013) 2247–2251. [42] J.-P. Andreassen, Growth and aggregation phenomena in precipitation of calcium carbonate, Department of Chemical Engineering Norwegian University of Science and Technology, 2001. [43] D. Volodkin, N. Larionova, G. Sukhorukov, Protein Encapsulation via Porous CaCO3 Microparticles Templating, Biomacromolecules 5 (2004) 5, 1962–1972. [44] D. Volodkin, R. von Klitzing, H. Möhwald, Pure protein microspheres by calcium carbonate templating, Angew. Chem. 122 (2010) 9444–9447. [45] Y. Han, G. Hadiko, M. Fuji, M. Takahashi, Influence of initial CaCl2 concentration on the phase and morphology of CaCO3 prepared by carbonation, J. Mater. Sci. 41 (2006) 4663–4667. [46] J. Watanabe, M. Akashi, Controlled deposition of calcium carbonate particles on porous membranes by using alternating current system, J. Colloid Interface Sci. 327 (2008) 44–50. [47] Y.-H. Won, H.S. Jang, D.-W. Chung, L.A. Stanciu, Multifunctional calcium carbonate microparticles: synthesis and biological applications, J. Mater. Chem. 20 (2010) 7728–7733. [48] H.W. Morse, J.D.H. Donnay, Optics and structure of three-dimensional spherulites, Am. Mineral. 21 (1936) 391–426. [49] S.-H. Yu, H. Cölfen, M. Antonietti, Polymer-controlled morphosynthesis and mineralization of metal carbonate superstructures, J. Phys. Chem. B 107 (2003) 7396–7405. [50] N. Gehrke, H. Cölfen, N. Pinna, M. Antonietti, N. Nassif, Superstructures of calcium carbonate crystals by oriented attachment, Cryst. Growth Des. 5 (2005) 1317–1319. [51] B.R. Heywood, S. Rajam, S. Mann, Oriented crystallization of CaCO3 under compressed monolayers. Part 2. — morphology, structure and growth of immature crystals, J. Chem. Soc. Faraday Trans. 87 (1991) 735–743. [52] L. Qi, J. Li, J. Ma, Biomimetic morphogenesis of calcium carbonate in mixed solutions of surfactants and double-hydrophilic block copolymers, Adv. Mater. 14 (4) (2002) 300–303. [53] F. Manoli, J. Kanakis, P. Malkaj, E. Dalas, The effect of aminoacids on the crystal growth of calcium carbonate, J. Cryst. Growth 236 (2002) 363–370. [54] A.G. Xyla, E.K. Giannimaras, P.G. Koutsoukos, The precipitation of calcium carbonate in aqueous solutions, Colloids Surf. 53 (1991) 241–255. [55] L.N. Plummer, E. Busenberg, The solubilities of calcite, aragonite and vaterite in CO2– H20 solutions between 0 and 90 °C, and an evaluation of the aqueous model for the system CaCO3–CO2–H2O, Geochim. Cosmochim. Acta 46 (1982) 1011–1040.

657

[56] S. Kirboga, M. Oner, Investigation of calcium carbonate precipitation in the presence of carboxymethyl inulin, Cryst. Eng. Comm. 15 (2013) 3678–3686. [57] Y. Liu, Y. Cui, H. Mao, R. Guo, Calcium carbonate crystallization in the presence of casein, Cryst. Growth Des. 12 (2012) 4720–4726. [58] E. Dalas, S.N. Koklas, The overgrowth of vaterite on functionalized styrenebutadiene copolymer, J. Cryst. Growth 256 (2003) 401–406. [59] Y. Kitano, N. Kanamori, A. Tokuyama, Effects of organic matter on solubilities and crystal form of carbonates, Am. Zool. 9 (3) (1969) 681–688. [60] E. Dalas, P. Klepetsanis, P.G. Koutsoukos, The overgrowth of calcium carbonate on poly(vinyl chloride-co-vinyl acetate-co-maleic acid), Langmuir 15 (1999) 8322–8327. [61] C.-L. Yao, W.-H. Xu, A.-M. Ding, J.-M. Zhu, Sucrose/bovine serum albumin mediated biomimetic crystallization of calcium carbonate, J. Chem. Sci. 121 (1) (2009) 89–93. [62] N. Qiu, H. Yin, B. Ji, N. Klauke, A. Glidle, Y. Zhang, H. Song, L. Cai, L. Ma, G. Wang, L. Chen, W. Wang, Calcium carbonate microspheres as carriers for the anticancer drug camptothecin, Mater. Sci. Eng. C 32 (2012) 2634–2640. [63] M. De Reggi, B. Gharib, L. Patard, V. Stoven, Lithostathine, the presumed pancreatic stone inhibitor, does not interact specifically with calcium carbonate crystals, J. Biol. Chem. 273 (9) (1998) 4967–4971. [64] S.-C. Huang, K. Naka, Y. Chujo, Effect of molecular weights of poly(acrylic acid) on crystallization of calcium carbonate by the delayed addition method, Polym. J. 40 (2) (2008) 154–162. [65] A. L. Porter, W. J. Wilson, Manufacture of precipitated calcium carbonate of improved color and stable crystalline form, US Patent, Jun 18, 1997. [66] P. Malkaj, J. Kanakis, E. Dalas, The effect of leucine on the crystal growth of calcium carbonate, J. Cryst. Growth 266 (2004) 533–538. [67] Z.-H. Xue, S.-X. Dai, B.-B. Hu, Z.-L. Du, Effect of Langmuir monolayer of bovine serum albumin protein on the morphology of calcium carbonate, Mater. Sci. Eng. C 29 (2009) 1998–2002. [68] J. Kanakis, E. Dalas, The crystallization of vaterite on fibrin, J. Cryst. Growth 219 (2000) 277–282. [69] R. Lakshminarayanan, E. Ooi Chi-Jin, X.J. Loh, R.M. Kini, S. Valiyaveettil, Purification and characterization of a vaterite-inducing peptide, pelovaterin, from the eggshells of Pelodiscus sinensis (Chinese Soft-shelled turtle), Biomacromolecules 6 (2005) 1429–1437. [70] J.J.J.M. Donners, B.R. Heywood, E.W. Meijer, R.J.M. Nolte, N.A.J.M. Sommerdijk, Control over calcium carbonate phase formation by dendrimer/surfactant templates, Chem. Eur. J. 8 (11) (2002) 2561–2567. [71] B.V. Parakhonskiy, A. Haase, R. Antolini, Sub-micrometer vaterite containers: synthesis, substance loading, and release, Angew. Chem. Int. Ed. 51 (2012) 1195–1197. [72] F.T. Wall, J.W. Drenan, Gelation of polyacrylic acid by divalent cations, J. Polym. Sci. 7 (1951) 83–88. [73] K.J. Henderson, T.C. Zhou, K.J. Otim, K.R. Shull, Ionically cross-linked triblock copolymer hydrogels with high strength, Macromolecules 43 (2010) 6193–6201. [74] A. Packter, S. Sabir, The precipitation of alkaline-earth metal polyacrylate hydrate powders from aqueous solution: ionic equilibria, precipitate compositions and morphologies, Cryst. Res. Technol. 21 (2) (1986) 195–200. [75] Z. Fengju, Crystallization of calcium carbonate in hydrogels in presence of mesotetrakis (4hydroxylphenyl) porphyrin, J. Cent. South Univ. 19 (7) (2012) 1802–1807. [76] D. Rautaray, A. Ahmad, M. Sastry, Biosynthesis of CaCO3 crystals of complex morphology using a fungus and an actinomycete, J. Am. Chem. Soc. 125 (48) (2003) 14656–14657. [77] M. Devenney, M. Fernandez, S. O Morgan, Non-cementitious compositions comprising vaterite and methods thereof, US Patent, Oct 31, 2008. [78] Z.G. Cui, C.F. Cui, Y. Zhu, B.P. Binks, Multiple phase inversion of emulsions stabilized by in situ surface activation of CaCO3 nanoparticles via adsorption of fatty acids, Langmuir 28 (1) (2012) 314–320. [79] H. Ohgushi, M. Okumura, T. Yoshikawa, K. Inboue, N. Senpuku, S. Tamai, E.C. Shors, Bone formation process in porous calcium carbonate and hydroxyapatite, J. Biomed. Mater. Res. 26 (7) (1992) 885–895. [80] J. Nakamura, G. Poologasundarampillai, J.R. Jones, T. Kasuga, Tracking the formation of vaterite particles containing aminopropyl-functionalized silsesquioxane and their structure for bone regenerative medicine, J. Mater. Chem. B 1 (2013) 4446–4454. [81] M.G. Ma, J.F. Zhu, Recent progress on fabrication of calcium-based inorganic biodegradable nanomaterials, Recent Pat. Nanotechnol. 4 (2010) 164–170. [82] M. Brito, E. Case, W.M. Kriven, J. Salem, D. Zhu, A.C. Tas, Use of vaterite and calcite in forming calcium phosphate cement scaffolds, Ceram. Eng. Sci. Proc. 28 (9) (2009) 135–150. [83] T.V. Bukreeva, I.V. Marchenko, T.N. Borodina, I.V. Degtev, S.L. Sitnikov, Y.V. Moiseeva, N.V. Gulyaeva, M.V. Kovalchuk, Calcium carbonate and titanium dioxide particles as a basis for container fabrication for brain delivery of compounds, Dokl. Phys. Chem. 440 (1) (2011) 165–167. [84] A.M. Yashchenok, D. Borisov, B.V. Parakhonskiy, A. Masic, B. El Pinchasik, H. Möhwald, A.G. Skirtach, Nanoplasmonic smooth silica versus porous calcium carbonate bead biosensors for detection of biomarkers, Ann. Phys. 524 (11) (2012) 723–732. [85] G.B. Sukhorukov, D.V. Volodkin, A. Günther, A.I. Petrov, D.B. Shenoy, H. Möhwald, Porous calcium carbonate microparticles as templates for encapsulation of bioactive compounds, J. Mater. Chem. 14 (2004) 2073–2081. [86] A.I. Petrov, D.V. Volodkin, G.B. Sukhorukov, Protein–calcium carbonate coprecipitation: a tool for protein encapsulation, Biotechnol. Prog. 21 (3) (2005) 918–925. [87] D.V. Volodkin, A.I. Petrov, M. Prevot, G.B. Sukhorukov, Matrix polyelectrolyte microcapsules: new system for macromolecule encapsulation, Langmuir 20 (8) (2004) 3398–3406.

658

D.B. Trushina et al. / Materials Science and Engineering C 45 (2014) 644–658

[88] Z. She, C.X. Wang, J. Li, G.B. Sukhorukov, M.N. Antipina, Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer microcapsules and its controlled release for enhancing cell proliferation, Biomacromolecules 13 (7) (2012) 2174–2180. [89] L.J. De Cock, S. De Koker, B.G. De Geest, J. Grooten, C. Vervaet, J.P. Remon, G.B. Sukhorukov, M.N. Antipina, Polymeric multilayer capsules in drug delivery, Angew. Chem. Int. Ed. 49 (2010) 6954–6973. [90] Z. She, M.N. Antipina, J. Li, G.B. Sukhorukov, Mechanism of protein release from polyelectrolyte multilayer microcapsules, Biomacromolecules 11 (5) (2010) 1241–1247. [91] N.L. Yakovlev, M.V. Kiryukhin, M.N. Antipina, T.T. Susanto, S. Ravi, M. Adithyavairavan, G.B. Sukhorukov, Secondary ion mass spectrometry of macromolecules loading in individual polyelectrolyte multilayer microcapsules, Aust. J. Chem. 64 (9) (2011) 1293–1296.

[92] S. De Koker, B.G. De Geest, S.K. Singh, R. De Rycke, T. Naessens, Y. Van Kooyk, J. Demeester, S.C. De Smedt, J. Grooten, Polyelectrolyte microcapsules as antigen delivery vehicles to dendritic cells: uptake, processing, and cross-presentation of encapsulated antigens, Angew. Chem. Int. Ed. 48 (45) (2009) 8485–8489. [93] I. Marchenko, A. Yashchenok, T. Borodina, T. Bukreeva, M. Konrad, H. Möhwald, A. Skirtach, Controlled enzyme-catalyzed degradation of polymeric capsules templated on CaCO3: influence of the number of LbL layers, conditions of degradation, and disassembly of multicompartments, J. Control. Release 162 (2012) 599–605. [94] A. Yashchenok, B. Parakhonskiy, S. Donatan, D. Kohler, A. Skirtach, H. Möhwald, Polyelectrolyte multilayer microcapsules templated on spherical, elliptical and square calcium carbonate particles, J. Mater. Chem. 1 (2013) 1223–1228. [95] M.N. Antipina, G.B. Sukhorukov, Remote control over guidance and release properties of composite polyelectrolyte based capsules, Adv. Drug Deliv. Rev. 63 (9) (2011) 716–729.