Chapter 10: Other Developments and Perspectives in the Fabrication of New Materials Facilitated by Freezing and Freeze‐drying – Ice Templating and Freeze-Drying for Porous Materials and Their Applications

Other Developments and Perspectives in the Fabrication of New Materials Facilitated by Freezing and Freeze‐drying

The ice‐templating approach for the preparation of porous and functional materials is a two‐stage process. The templates are first created by a freezing step and then removed in the second stage, usually by a freeze‐drying process. Ice templating is often applied to solutions or suspensions (mostly water‐based), with the solutes or dispersants to determine what materials may be fabricated. The ice‐templating method may be also used in systems based on organic solvents or in combination with other techniques, in order to produce materials with better control in porosity/morphology or more functions. Some of these have been mentioned in previous chapters but will be highlighted in this chapter. There are also developments in preparation of new materials, which are promoted by the freezing stage or the freeze‐drying step. These will be also discussed. A general summary and perspective is given at the end of the chapter.

10.1 Combining Ice‐templating and Other Techniques

10.1.1 Ice Templating and Emulsion Templating

Emulsion templating is an effective route to the preparation of porous materials. When increasing the volume of the internal droplets to above 74.05 v/v%, the emulsions are called high internal phase emulsions (HIPEs). HIPEs can be used to fabricate highly interconnected macroporous materials [1]. While the continuous phase containing monomers may be polymerized to lock in the emulsion structure [2], the emulsions can be frozen and freeze‐dried to remove the solvents from both the continuous phase and droplet phase. The resulting porous materials exhibit both emulsion‐templated cellular pores and ice‐templated pores [3]. By choosing suitable precursor materials, the scaffolds prepared via the combined approaches can be better for targeted applications, e.g. for bone tissue engineering [4]. In principle, any emulsion can be frozen and freeze‐dried. However, most reports are based on oil‐in‐water (O/W) emulsions [1]. Considering the limitations of the freeze‐dryer used, the selected organic solvents should have relatively high boiling points so that the freeze‐drying process can be completed without damage or partial collapse of the emulsion‐templated structure.

In addition to the emulsions formed with surfactants or polymers, Pickering emulsions (where particles are used as the stabilizers) may be freeze‐dried to produce porous structures. For example, a Pickering emulsion was formed by emulsifying hexane into aqueous medium containing silica nanoparticles (24 wt%) and poly(N‐isopropylacrylamide)‐based microgels (0.8 wt%). The emulsion was freeze‐dried and then calcined at 950 °C for 2 h [5]. As shown in Figure 10.1, the resulting material exhibits emulsion‐templated macropores (10–30 μm), interconnected windows (3–5 μm), and nanoporous walls (80 nm, from the microgel templating). Starch granules were also employed to form emulsion. When non‐volatile oils such as Miglyol 812 and peanut oil were used as the internal phase, the freeze‐drying process produced oil‐containing (as high as 80%) powders that could be readily reconstituted [6]. The porous polymer structures fabricated by emulsion‐freeze‐drying have been used as scaffolds to absorb organic solution or oils. In the former case, after evaporation of organic solvent, organic nanoparticles were formed within the porous materials. Aqueous nanoparticle (organic or drug) dispersions are produced upon dissolution of the composites [7, 8]. When oils (both volatile and non‐volatile) are absorbed into the porous polymer, the composites can be readily dissolved, resulting in instant formation of emulsions [9].

Figure 10.1 SEM images show the porous structures prepared by freeze‐drying a Pickering emulsion using silica nanoparticles (40 nm) and polymer microgel (250 nm) as stabilizers. (a) and (b) The interconnected emulsion‐templated cellular pores; (c) and (d) The pore structure of the cellular walls after removing microgel particles by calcination at 950 °C for 2 h.

Source: Li et al. 2010 [5]. Reprinted with permission from Royal Society of Chemistry.

Porous materials are produced when freeze‐drying the emulsions where the internal droplets consist of solvent only. When a solution is emulsified into another solution containing surfactant and/or polymer, the freeze‐drying process can lead to in situ formation of nanoparticles or microparticles within the porous structures. This has been demonstrated by the formation of organic nanoparticles or drug nanoparticle within porous polymers [10, 11]. An organic solution (hydrophobic dye Oil Red O dissolved in cyclohexane) was dispersed in aqueous solution containing surfactant and hydrophilic polymer poly(vinyl alcohol) (PVA) [10]. Similarly, organic solutions containing hydrophobic drug compounds could be used [11]. The freeze‐drying of the emulsions led to the formation of hydrophobic nanoparticles within porous PVA, all in one step. The porous PVA could be dissolved to release the nanoparticles and stable aqueous nanoparticle dispersions were formed instantly. If monomers instead of polymers are present in the continuous phase, the monomers can be polymerized and crosslinked first, followed by emulsion freeze‐drying. The organic nanoparticles formed may be either released by simple diffusion or facilitated by triggers such as temperature change [12]. However, porous microparticles embedded in the porous matrix can be formed when a hydrophobic polymer is dissolved in the internal organic phase, after freeze‐drying the emulsions. A directional freezing process results in the production of uniquely aligned porous microparticles [13]. In a recent progress, emulsions have been formed from lightly crosslinked branched block copolymers only. The emulsion‐freeze‐drying approach was then employed to generate drug nanoparticles with high yield [14].

10.1.2 Gelation/Crosslinking and Ice Templating

Conventionally, solutions or suspensions are directly freeze‐dried. This usually produces powders or fragile porous materials. In order to enhance the mechanical stability, the solutions or suspensions may be crosslinked physically or chemically and subsequently subjected to a freeze‐drying process. Gelatin is one of the most commonly used gelation systems, particularly when preparing porous ceramics. Gelatin can be dissolved in warm solution and the gelation conveniently occurs when the warm solution/suspension cools down [15]. Additional templates such as salt particles may be incorporated to tune the porosity of the freeze‐dried scaffolds [16]. Another widely used gelation system is the freezing and thawing of PVA solution. The gelation is induced by hydrogen bonding and crystallization of contacted chains. The number of freeze–thaw cycles can influence the crystallites' crosslinking density and the strength of the gels. The freeze–thaw process is usually carried out in a freezer (−20 °C) and then allowed to thaw at room temperature. Recently, when a directional freezing process was employed during the freezing step, PVA hydrogel with gradient stiffness was produced and was further used to investigate stem cell differentiation and cell migration in terms of scaffold stiffness [17]. Monomer solutions (e.g. resorcinol–formaldehyde resins) or emulsions containing monomers in the continuous phase [12] can be polymerized and crosslinked. The subsequent freeze‐drying process produces highly porous materials with minimal shrinkage. Similarly, a sol–gel process (e.g. from silica sol) can be combined with a freeze‐drying process to fabricate stable monoliths with well‐defined ice‐templated macropores [18].

10.1.3 Ice Templating with Green Solvents

There are many occasions where water cannot be used as solvent. For example, hydrophobic polymers or organic compounds are insoluble in water. The compounds or the biomolecules may be hydrolysed or destabilized by the presence of water. This is the reason for organic solutions or suspensions being employed in ice‐templating processes [19]. In an effort to replace organic solvents with a green solvent, sugar acetate solutions in compressed CO2 were prepared (a high pressure vessel with valves required) and then frozen in liquid nitrogen [20]. Unlike the use of organic solvents where the freeze‐drying step is usually required to remove the frozen solvent, the frozen CO2 solution could be easily allowed to warm up (e.g. in a fume hood at room temperature) and released as gaseous CO2 with the valves open [20]. There is no residual solvent in the resulting material and, therefore, this method can be potentially very useful for biomaterials. However, the limitations for this method are that high pressure vessels or reactors have to be used and that not many compounds or polymers are soluble in compressed CO2 or swollen by CO2.

Another type of green solvents is ionic liquids (ILs). ILs are usually regarded as molten salts with melting points below 373 K [21]. The selection of anions and cations is crucial as the interactions between them destabilize the tendency to form solid‐phase crystals. The common properties of ILs include high electrical conductivity, liquid phase in a wide temperature range, and negligible vapour pressure [21, 22]. ILs are often regarded as green solvents because of the negligible vapour pressure. For the same reason, it is not possible to remove ILs by freeze‐drying. Gutièrrez et al. developed a method to incorporate bacteria in deep‐eutectic solvents (DES) via freeze‐drying for enhanced biocatalytic reactions [23]. DES are a class of ILs obtained by complexion of quaternary ammonium salts with hydrogen bond donors. The presence of water hydrates the ions and destroys the properties of the ILs. By dispersing bacteria in minimal media in an aqueous solution of DES, the freeze‐drying process then removes the water and incorporates the bacteria in pure DES [23].

The freeze–thaw process has been applied to lignocellulose–IL solutions. Lignocellulose aerogels were produced after rinsing ILs with acetone [24] or water [25], followed by supercritical CO2 drying. The processing parameters included freeze–thaw temperatures (e.g. −20 to 20 °C [24, 25], −196 to 20 °C), cycles and frequency of freeze–thaw, and solvents used to wash ILs. These parameters could make a difference in producing 2D sheet‐like structures or 3D fibrous networks [24, 25]. Song et al. employed a directional freezing process to make aligned porous scaffolds of PVA containing halloysite nanotubes [26]. The scaffolds could absorb the IL 1‐butyl‐3‐methylimidazolium tetrafluoroborate, generating a composite with anisotropic ionic conductivity. The ionic conductivity reached 5.2 × 10−3 S cm−1 at 30 °C in the direction parallel to the freezing direction, which was more than 500 times higher than the value obtained in the direction perpendicular to the freezing direction [26].

10.2 Freezing‐induced Self‐assembly

The self‐assembly of particles, including nanospheres, nanowires, and platelets, can be facilitated by the freezing process. The self‐assembly is the result of particle concentration and exclusion from the moving ice front. Recently, Albouy et al. reported the self‐assembly of amphiphilic molecules, the commercial block copolymer P123, induced by the freezing process [27]. The freezing process was monitored using in situ small angle X‐ray scattering (SAXS). At the start, there were only unimers. The freezing ice front excluded P123 molecules and concentrated P123 and led to the self‐assembly of P123 micelles to form ordered mesophases (Figure 10.2). Ordered structures such as hexagonally closed packed (hcp) sphere aggregates and 2D hexagonal phase were detected by SAXS. This phenomenon is similar to the evaporation‐induced surfactant self‐assembly where the evaporation of the solvent concentrates the solution and induces the self‐assembly of the surfactant molecules into different mesophases [28]. The evolution of P123 self‐assembly induced by the freezing process was summarized using a concentration–temperature diagram [27]. This finding may be very useful for the construction of soft matters and mesoporous materials.

Figure 10.2 Scheme showing the freezing‐induced self‐assembly of P123 in water in a concentration–temperature diagram.

Source: Albouy et al. 2017 [27]. Reprinted with permission from Royal Society of Chemistry.

10.3 Reaction and Polymerization in Frozen Solutions

Chemical reactions usually occur smoothly and fast under the freely diffusing condition in homogeneous solutions. However, some reactions have been reported to be accelerated in the frozen state [29]. It should be pointed out that a frozen solution is not a frozen solid. For solutions containing two or more components, the frozen solution usually refers to the temperature below the freezing point of the solvent while the frozen solid state indicates the solution frozen below the eutectic point (Figure 10.3) [29]. In the frozen state, due to the effect of freezing point depression resulting from solution concentration, there are concentrated liquid solutions still present, which may accelerate the reactions in spite of low temperatures [29, 30]. For a solution containing both water and an organic solvent such as methanol, below the ice‐freezing temperature, there are puddles of methanol that can induce reactions in frozen solutions [31]. The other acceleration mechanisms include: (i) the position effect induced by solvent crystallization and orientation of reactants; (ii) the catalytic activity offered by the surface of the frozen solvent; and (iii) enhanced proton or electron transfer in the frozen solution [32, 33]. For accelerated reactions in frozen state, it is usually difficult to point out the exact mechanism. It is possible that multiple mechanisms may contribute to the acceleration. Naidu et al. reported the highly chemoselective Michael addition of amines and thiols to the dehydroalanine side chain of nocathiacins in water with good yields. The reactions were carried out at −20 °C. The selectivity and yields were much better than the reactions performed at room temperature [34]. Accelerated glycosylation using thiomethyl glycosides in p‐xylene was observed when the reactions were performed below the freezing point of p‐xylene. High yields were recorded in frozen p‐xylene while only marginal yields were obtained for the reactions at room temperature [35].

Figure 10.3 Diagram of a solution containing two or more components under different states.

Source: Adapted from Pincock 1969 [29].

Accelerated polymerization has also been reported in frozen solvents. For example, the polymerization rates of N‐carboxyamino acid anhydrides were found to be at least 10 times higher in frozen dioxane between +5 °C and −26 °C than in liquid systems [32]. The ice crystals may be also employed as templates in fabricating nanofibers and 3D porous structures. Ma et al. fabricated polyaniline microflakes by freezing aqueous solution containing H4SiW12O40, FeCl3 and aniline in freezer at −10 °C for 20 days [36]. The solutes were excluded from the ice crystals and polymerized between the layered ice crystals, producing microflakes. At a higher magnification by electron microscopic imaging, it was revealed that the microflakes consisted of polyaniline nanofibers in the range of 22–32 nm [36].

Interfacial polymerization involving the frozen solvent crystals has been used to produce porous or nanostructured materials. Qi et al. prepared highly conductive polypyrrole films by freezing a two‐phase system (pyrrole in cyclohexane + water containing ammonium persulfate (APS) as oxidant and HCl as dopant) in a freezer at −20 °C for 4 days [37]. Figure 10.4 shows schematically how the interfacial polymerization method works. After freezing, liquid aniline is excluded from frozen cyclohexane and fills the interstices between ice crystals due to gravity and capillary effects. The oxidant and dopant are also excluded from the ice crystals that initiate the redox polymerization of pyrrole. The polypyrrole film prepared this way showed a high conductivity up to 2000 S cm−1 [37]. When a solvent with lower melting point is mixed with aqueous solution and a frozen polymerization is followed, polymer capsules may be fabricated. For example, when diethyl ether was added and mixed with aqueous solution containing H4SiW12O40, FeCl3 and aniline and the resulting suspensions were frozen at −18 °C for 20 days, hollow hemispheres of polyaniline were produced (Figure 10.5) [38]. This resulted from the droplets of diethyl ether in ice crystals and the excluded solutes reacting at the interface between ice and diethyl ether droplets. The formed polyaniline nanoparticles at the curved interface precipitated to eventually generate hollow hemispheres [38].

Figure 10.4 Schematic shows the preparation of polypyrrole films via freezing interfacial polymerization.

Source: Qi et al. 2012 [37]. Reprinted with permission from Royal Society of Chemistry.

Figure 10.5 Polyaniline hemispheres synthesized via an ice‐templating method with the addition of diethyl ether into the aqueous solution containing reactants. (a) An overview of the hemispheres, with the inset showing the surface of one hemisphere. (b) The magnified internal structure of one hemisphere.

Source: Ma et al. 2010 [38]. Reprinted with permission from John Wiley and Sons.

Wang et al. reported the formation of uniform polyaniline nanotubes by combining freezing and nanorod templating to control the diffusion of aniline and APS at the polyaniline interface [39]. Aniline and amino acids were complexed to form nanorods in the solution. After freezing, APS was excluded from the ice crystals and diffused to the nanorods for the reaction with aniline. As the reaction occurred in the frozen solution, the diffusion of both aniline and APS across the polyaniline interface was similar to the preparation of hollow inorganic nanotubes via the Kirkendall effect. As shown in Figure 10.6, these polyaniline nanotubes are quite uniform, with an average outer diameter of 45 nm and inner diameters in the range of 5–10 nm. N‐doped carbon nanotubes could be readily formed by carbonization of polyaniline nanotubes in argon at 800 °C [39].

Figure 10.6 The morphology of polyaniline nanotubes synthesized via a frozen polymerization approach. (a) and (b) SEM images at different magnifications. (c) and (d) TEM images at different magnifications. The inset shows the XRD pattern of the nanotubes.

Source: Wang et al. 2015 [39]. Reprinted with permission from John Wiley and Sons.

Cryogels have been widely investigated by frozen polymerization, which is covered in Chapter 4. Instead of simply placing the solutions in a freezer for extended times, UV‐facilitated frozen polymerization has been used [40, 41]. These systems usually contain acrylate monomers and photoinitiators. This method can produce highly crosslinked and strong porous polymers or anisotropic hydrogels, templated from the orientated ice crystals [40, 41].

10.4 Ice‐templated Hierarchically Porous Materials Containing Micropores

Owing to the size of the ice crystals, ice‐templated materials always exhibit macropores in the range of microns. By choosing different additives, e.g. dextran, it is possible to reduce the ice‐templated pores to the nanometer range [42]. By using mixing solvents at eutectic points, mesopores in ice‐templated materials can be generated [43]. Mesopores may be also formed from the interstitial spaces between packed particles after freeze‐drying particle suspensions [44]. However, by all means, it is highly challenging to generate micropores in the ice‐templated materials (i.e. with the presence of ice‐templated pores) although the freeze‐drying process is effective in producing aerogels or microporous metal–organic frameworks (MOFs) [45, 46].

This issue may be addressed by applying the ice‐templating method to soluble microporous materials, the precursors of microporous materials, or the suspensions of particles containing micropores. There are many types of microporous materials, for example, zeolites, carbon, polymers of intrinsic microporosity (PIM) [47], MOFs [48], organic cages, and covalent organic frameworks (COFs) [49]. The ice‐templating process always begins with a solution or suspension. It is therefore straightforward to directly freeze‐dry the suspensions of the above‐mentioned particles with microporosity. This can fabricate the ice‐templated materials with microporosity. However, there is a disadvantage associated with this process. Because surfactants and polymeric stabilizers are usually required to form stable suspensions before the freeze‐drying process, the presence of these additives may block the micropores or at least reduce the microporosity proportionally.

The ice‐templating approach by processing solutions can address this problem. However, many of the microporous materials are crosslinked or frameworks and they are insoluble in common solvents. These include zeolites, carbon, COFs, and MOFs. Some of the microporous materials, organic cages and PIMs can be dissolved in organic solvents. As such, these microporous materials are dissolved in organic solvents and processed via the ice‐templating procedures to produce hierarchical monoliths with microporosity. Owing to its high solubility in chloroform, the organic cage CC13 solution in chloroform was directionally frozen and freeze‐dried to generate a monolith [50]. Figure 10.7a and b shows the aligned macropores by scanning electron microscopic (SEM) imaging. This macroporosity, with the pore sizes in a wide range but mainly around 100 μm, is also confirmed by Hg intrusion porosimetry (Figure 10.7c). The gas sorption data based on H2 and N2 uptake show the presence of micropores (Figure 10.7d). H2 uptake at 77 K and 1 bar was around 4.5 mmol g−1 while N2 uptake was only about 1.9 mmol g−1 with a BET surface of 80 m2 g−1. The surface area is much lower than that of the crystalline CC13. This is attributed to the constraining of the pathway through the structure by the loss of order, limiting the access of relatively large molecules. Similarly, PIM‐1 was dissolved in chloroform. After directional freezing and freeze‐drying of the solution, a monolith with well‐aligned macropores and porous walls was formed. This monolith exhibited an intrusion volume of 4.21 cm3 g−1 and a BET surface area of 766 m2 g−1. Mesopores up to 30 nm and a sharp peak around 1 nm were obtained from N2 sorption for this material [50].

Figure 10.7 The aligned porous organic cage (CC13) prepared by directional freezing and freeze‐drying of CC13 solution in chloroform. (a) and (b) The pore structure. (c) The macropore size distribution measured by Hg intrusion porosimetry. (d) The H2 and N2 uptake of the CC13 monolith.

Source: Ahmed et al. 2015 [50]. Reprinted with permission from Royal Society of Chemistry.

HKUST‐1 is one of the earliest and most widely investigated MOFs and can be synthesized under mild conditions. Ahmed et al. prepared HKUST‐1 monolith in a steel column by simply mixing the precursor powders of copper acetate and benzene tricarboxylate (BTC), soaked with a mixture solvent of ethanol:H2O, and then heated at mild temperatures of 25–120 °C [51]. The synthesized monolith showed a surface area of 1240 m2 g−1 and enhanced mechanical stability. In addition to the intrinsic micropores of HKUST‐1, this monolith exhibited mesopores that were generated from the aggregated nanoparticles during the synthesis. An ice‐templating method was further developed to fabricate HKUST‐1 monoliths with macropores [50]. In this method, the solution of copper acetate + BTC in dimethyl sulfoxide (DMSO) was directionally frozen and freeze‐dried to produce a monolith with the ice‐templated aligned pores. The monolith showed the typical powder X‐ray diffraction (PXRD) pattern of HKUST‐1 but the crystallinity could be further improved by post‐treatment in ethanol at 120 °C. As shown in Figure 10.8a and b, the aligned macropores can be clearly seen while the pore wall surface is quite smooth. The N2 sorption analysis gave a surface area of 870 m2 g−1, a micropore volume of 0.406 cm3 g−1 (with a sharp peak around 1 nm, Figure 10.8c), and a mesopore volume of 0.271 cm3 g−1. The bimodal macropore size distribution (aligned macropores around 10 μm and the macropores of 0.4 μm in the wall) was characterized by Hg intrusion porosimetry and is shown in Figure 10.8d [50]. A high intrusion volume of 8.30 cm3 g−1 was obtained. It was believed that the monolith was formed during the freeze‐drying stage because the freezing process was fast and the temperature (in liquid nitrogen) was very low. Indeed, freeze‐drying is an effective technique for the synthesis of co‐crystals and the manufacture of pharmaceutical dosage forms. The co‐crystals can be formed via the amorphous phase during the solvent sublimation stage for the amorphous materials with glass transition temperatures at or below ambient temperature [52].

Figure 10.8 Characterization of aligned porous MOF (HKUST‐1) monolith fabricated by an ice‐templating approach. (a) The pore structure. (b) The surface morphology. (c) The N2 sorption isotherm with the inset showing the micropore size distribution. (d) The macropore size distribution by Hg intrusion porosimetry.

Source: Ahmed et al. 2015 [50]. Reprinted with permission from Royal Society of Chemistry.

10.5 General Summary and Perspectives

Freezing and freeze‐drying are the key steps of the ice‐templating method although the frozen solvent may be removed by other methods instead of freeze‐drying. Freezing of solutions and colloids has been known in nature (e.g. sea ice, frost heaving) and widely used in cryopreservation and food engineering (e.g. ice cream, frozen dessert) [53]. With regards to freezing, freeze‐drying has been a highly effective drying technique for pharmaceutical formulations and materials science. In this book, we have focused on the use of ice templating and freeze‐drying for different types of porous materials and the use of freeze‐drying for pharmaceutical and food studies is also described. The emphasis has been on the fabrication methods, processing parameters, and description of the typical applications of each type of ice‐templated materials. We believe that most types of the ice‐templated materials are covered in this book. The aim is to give the readers a clear picture of how the ice‐templating method may be used for preparation of various materials. In spite of our best efforts, there is a possibility that some unique materials fabricated by ice templating may not be included. Hopefully, this will be improved in a future edition.

With the progress so far, ice templating has been demonstrated to be highly efficient for materials fabrication. The uniqueness of this method lies in its simplicity and versatility. The prepared materials exhibit highly interconnected pore structures, anisotropic pores (aligned channels or layered structure), and fibrous networks, which may be further used to produce strong and functional composites or other nanostructured materials. Other procedures or techniques may be employed in combination with ice templating to enhance mechanical properties or offer additional functionalities. However, the challenges remain on the production of large‐scale materials with reproducible pore morphology and porosity. Formulations, processing parameters, and novel freezing procedures/devices will be continuously developed and optimized for this purpose. To better control the structure of materials, the development of freezing theory and experimental observation to provide evidence for freezing mechanisms are still the essential part in the use of the ice‐templating method. For materials engineers and scientists, we believe the focus will be on selecting functional building blocks and developing methods and procedures to produce materials with required pore structure, strength, functionality and other properties for the target applications. Therefore, it is important to understand what materials and their characteristics are required and how the ice‐templating (freezing, freeze‐drying) method, or in combination with other techniques, may be developed accordingly to obtain the desired materials.


  1. 1 Zhang, H. and Cooper, A.I. (2005). Synthesis and applications of emulsion‐templated porous materials. Soft Matter 1: 107–113.
  2. 2 Zhang, H. and Cooper, A.I. (2002). Synthesis of monodisperse emulsion‐templated polymer beads by oil‐in‐water‐in‐oil (O/W/O) sedimentation polymerization. Chem. Mater. 14: 4017–4020.
  3. 3 Qian, L., Ahmed, A., Foster, A. et al. (2009). Systematic tuning of pore morphologies and pore volumes in macroporous materials by freezing. J. Mater. Chem. 19: 5212–5219.
  4. 4 Sultana, N. and Wang, M. (2012). PHBV/PLLA‐based composite scaffolds fabricated using an emulsion freezing/freeze‐drying technique for bone tissue engineering: surface modification and in vitro biological evaluation. Biofabrication 4: 015003.
  5. 5 Li, Z., Wei, X., Ming, T. et al. (2010). Dual templating synthesis of hierarchical porous silica materials with three orders of length scale. Chem. Commun. 46: 8767–8769.
  6. 6 Marefati, A., Rayner, M., Timgren, A. et al. (2013). Freezing and freeze‐drying of Pickering emulsions stabilized by starch granules. Colloid Surf. A 436: 512–520.
  7. 7 Qian, L., Ahmed, A., and Zhang, H. (2011). Formation of organic nanoparticles by solvent evaporation within porous polymeric materials. Chem. Commun. 47: 10001–10003.
  8. 8 Roberts, A.D. and Zhang, H. (2013). Poorly water‐soluble drug nanoparticles via solvent evaporation in water‐soluble porous polymers. Int. J. Pharm. 447: 241–250.
  9. 9 Qian, L. and Zhang, H. (2010). Direct formation of emulsions using water‐soluble porous polymers as sacrificial scaffolds. J. Chem. Technol. Biotechnol. 85: 1508–1514.
  10. 10 Zhang, H., Wang, D., Butler, R. et al. (2008). Formation and enhanced biocidal activity of water‐dispersible organic nanoparticles. Nat. Nanotechnol. 3: 506–511.
  11. 11 Grant, N. and Zhang, H. (2011). Poorly water‐soluble drug nanoparticles via an emulsion‐freeze‐drying approach. J. Colloid Interface Sci. 356: 573–578.
  12. 12 Zhang, H. and Cooper, A.I. (2007). Thermoresponsive “particle pumps”: activated release of organic nanoparticles from open‐cell macroporous polymers. Adv. Mater. 19: 2439–2444.
  13. 13 Zhang, H., Edgar, D., Murray, P. et al. (2008). Synthesis of porous microparticles with aligned porosity. Adv. Funct. Mater. 18: 222–228.
  14. 14 Wais, U., Jackson, A.W., Zuo, Y. et al. (2016). Drug nanoparticles by emulsion‐freeze‐drying via the employment of branched block copolymer nanoparticles. J. Control. Release 222: 141–150.
  15. 15 Fukushima, M. and Yoshizawa, Y. (2014). Fabrication of highly porous silica thermal insulators prepared by gelation‐freezing route. J. Am. Ceram. Soc. 97: 713–717.
  16. 16 Alizadeh, M., Abbasi, F., Khoshfetrat, A.B., and Ghaleh, H. (2013). Microstructure and characteristic properties of gelatin/chitosan scaffold prepared by a combined freeze‐drying/leaching method. Mater. Sci. Eng. C 33: 3958–3967.
  17. 17 Kim, T.H., An, D.B., Oh, S.H. et al. (2015). Creating stiffness gradient polyvinyl alcohol hydrogel using a simple gradual freezing‐thawing method to investigate stem cell differentiation behaviors. Biomaterials 40: 51–60.
  18. 18 Minaberry, Y. and Jobbágy, M. (2011). Macroporous bioglass scaffolds prepared by coupling sol‐gel with freeze drying. Chem. Mater. 23: 2327–2332.
  19. 19 Qian, L. and Zhang, H. (2011). Controlled freezing and freeze drying: a versatile route for porous and micro‐/nano‐structured materials. J. Chem. Technol. Biotechnol. 86: 172–184.
  20. 20 Zhang, H., Long, J., and Cooper, A.I. (2005). Aligned porous materials by directional freezing of solution in liquid CO2. J. Am. Chem. Soc. 127: 13482–13483.
  21. 21 Hayes, R., Warr, G.G., and Atkin, R. (2015). Structure and nanostructure in ionic liquids. Chem. Rev. 115: 6357–6426.
  22. 22 Ahmed, E., Breternitz, J., Groh, M.F., and Ruck, M. (2012). Ionic liquids as crystallisation media for inorganic materials. CrystEngComm 14: 4874–4885.
  23. 23 Gutièrrez, M.C., Ferrer, M.L., Yuste, L. et al. (2010). Bacteria incorporation in deep‐eutectic solvents through freeze‐drying. Angew. Chem. Int. Ed. 49: 2158–2162.
  24. 24 Li, J., Lu, Y., Yang, D. et al. (2011). Lignocellulose aerogel from wood‐ionic liquid solution (1‐allyl‐3‐methylimidazolium chloride) under freezing and thawing conditions. Biomacromolecules 12: 1860–1867.
  25. 25 Lu, Y., Sun, Q., Yang, D. et al. (2012). Fabrication of mesoporous lignocellulose aerogels from wood via cyclic liquid nitrogen freezing‐thawing in ionic liquid solution. J. Mater. Chem. 22: 13548–13557.
  26. 26 Song, H., Zhao, N., Qin, W. et al. (2015). High‐performance ionic liquid‐based nanocomposite polymer electrolytes with anisotropic ionic conductivity prepared by coupling liquid crystal self‐templating with unidirectional freezing. J. Mater. Chem. A 3: 2128–2134.
  27. 27 Albouy, P.A., Deville, S., Fulkar, A. et al. (2017). Freezing‐induced self‐assembly of amphiphilic molecules. Soft Matter 13: 1759–1763.
  28. 28 Brinker, C.J., Lu, Y., Sellinger, A., and Fan, H. (1999). Evaporation‐induced self‐assembly: nanostructures made easy. Adv. Mater. 11: 579–585.
  29. 29 Pincock, R.E. (1969). Reactions in frozen systems. Acc. Chem. Res. 2: 97–103.
  30. 30 Pincock, R.E. and Kiovsky, T.E. (1966). Kinetics of reactions in frozen solutions. J. Chem. Ed. 43: 358–360.
  31. 31 Wang, S.Y. (1961). Photochemical reactions in frozen solutions. Nature 190: 690–694.
  32. 32 Grant, N.H., Clark, D.E., and Alburn, H.E. (1966). Accelerated polymerization of N‐carboxyamino acid anhydrides in frozen dioxane. J. Am. Chem. Soc. 88: 4071–4074.
  33. 33 Chen, P. and Meyer, T.J. (1996). Electron transfer in frozen media. Inorg. Chem. 35: 5520–5524.
  34. 34 Naidu, N., Li, W., Sorenson, M.E. et al. (2004). Organic reactions in frozen water: Michael addition of amines and thiols to the dehydroalanine side chain of nocathiacins. Tetrahedron Lett. 45: 1059–1063.
  35. 35 Takatani, M., Nakano, J., Arai, M.A. et al. (2004). Accelerated glycosylation under frozen conditions. Tetrahedron Lett. 45: 3929–3932.
  36. 36 Ma, H., Gao, Y., Li, Y. et al. (2009). Ice‐templating synthesis of polyaniline microflakes stacked by one‐dimensional nanofibers. J. Phys. Chem. C 113: 9047–9052.
  37. 37 Qi, G., Huang, L., and Wang, H. (2012). Highly conductive free standing polypyrrole films prepared by freezing interfacial polymerization. Chem. Commun. 48: 8246–8248.
  38. 38 Ma, H., Li, Y., Gao, F. et al. (2010). Facile synthesis of polyaniline hemispheres in diethyl ether/ice mixture solvent and growth mechanism study. J. Polym. Sci. A 48: 3596–3603.
  39. 39 Wang, F., Wang, Z., Tana, M.B., and He, C. (2015). Uniform polyaniline nanotubes formation via frozen polymerization and application for oxygen reduction reactions. Macromol. Chem. Phys. 216: 977–984.
  40. 40 Barrow, M., Eltmimi, A., Ahmed, A. et al. (2012). Frozen polymerization for aligned porous structures with enhanced mechanical stability, conductivity, and as stationary phase for HPLC. J. Mater. Chem. 22: 11615–11620.
  41. 41 Barrow, M. and Zhang, H. (2013). Aligned porous stimuli‐responsive hydrogels via directional freezing and frozen UV initiated polymerization. Soft Matter 9: 2723–2729.
  42. 42 Nishihara, H., Iwamura, S., and Kyotani, T. (2008). Synthesis of silica‐based porous monoliths with straight nanochannels using an ice‐rod nanoarray as a template. J. Mater. Chem. 18: 3662–3670.
  43. 43 Borisova, A., De Bruyn, M., Budarin, V.L. et al. (2015). A sustainable freeze‐drying route to porous polysaccharides with tailored hierarchical meso‐ and macroporosity. Macromol. Rapid Commun. 36: 774–779.
  44. 44 Ahmed, A., Clowes, R., Myers, P., and Zhang, H. (2011). Hierarchically porous silica monoliths with tuneable morphology, porosity, and mechanical stability. J. Mater. Chem. 21: 5753–5763.
  45. 45 Eychmüller, A., Ziegler, C., Wolf, A. et al. (2017). Modern inorganic aerogels. Angew. Chem. Int. Ed. 56: 13200–13221.
  46. 46 Ma, L., Jin, A., Xie, Z., and Lin, W. (2009). Freeze drying significantly increases permanent porosity and hydrogen uptake in 4,4‐connected metal–organic frameworks. Angew. Chem. Int. Ed. 48: 9905–9908.
  47. 47 McKeown, N.B. and Budd, P.M. (2006). Polymers of intrinsic microporosity (PIMs): organic materials for membrane separations, heterogeneous catalysis and hydrogen storage. Chem. Soc. Rev. 35: 675–683.
  48. 48 Howarth, A.J., Peters, A.W., Vermeulen, N.A. et al. (2017). Best practices for the synthesis, activation, and characterization of metal−organic frameworks. Chem. Mater. 29: 26–39.
  49. 49 Slate, A.G. and Cooper, A.I. (2015). Functional‐led design of new porous materials. Science 348: 989–999.
  50. 50 Ahmed, A., Hasell, T., Clowes, R. et al. (2015). Aligned macroporous monoliths with intrinsic microporosity via a frozen‐solvent‐templating approach. Chem. Commun. 51: 1717–1720.
  51. 51 Ahmed, A., Forster, M., Clowes, R. et al. (2014). Hierarchically porous metal–organic framework monoliths. Chem. Commun. 50: 14314–14316.
  52. 52 Eddleston, M.D., Patel, B., Day, G.M., and Jones, W. (2013). Cocrystallization by freeze‐drying: preparation of novel multicomponent crystal forms. Cryst. Growth Des. 13: 4599–4606.
  53. 53 Deville, S. (2017). Freezing Colloids: Observations, Principles, Control, and Use. Springer International Publishing AG.