Hybrid Cryogels Research Articles

One-Shot Preparation of Polybasic Ternary Hybrid Cryogels Consisting of Halloysite Nanotubes and Tertiary Amine Functional Groups: An Efficient and Convenient Way by Freezing-Induced Gelation.

A convenient method for the preparation of polybasic ternary hybrid cryogels consisting of Halloysite nanotubes (HNTs) and tertiary amine functional groups by freezing-induced gelation is proposed. Ternary hybrid gels were produced via one-shot radical terpolymerization of 2-hydroxyethyl methacrylate (HEMA), 2-acrylamido-2-methyl-1-propane sulfonic acid (AMPS), and DEAEMA in the presence of HNTs. The equilibrium swelling in various swelling media and the mechanical properties of the produced ternary hybrid gels were analyzed to investigate their network structure and determine their final performance. The swelling ratio of HNT-free gels was significantly higher than the ternary hybrid gels composed of high amount of HNTs. The addition of HNTs to terpolymer network did not suppress pH- and temperature-sensitive behavior. While DEAEMA groups were effective for pH-sensitive swelling, it was determined that both HEMA and DEAEMA groups were effective in temperature-sensitive swelling. Ternary hybrid gels simultaneously demonstrated both negative and positive temperature-responsive swelling behavior. The swelling ratio changed considerably according to swelling temperature. Both DEAEMA and HEMA monomers in terpolymer structure were dominant in temperature-sensitive swelling. Mechanical tests in compression of both as-prepared and swollen-state demonstrated that strength and modulus of hybrid cryogels significantly increased with addition of HNTs without significant loss of mechanical strength. Ultimately, the results of the current system can benefit characterization with analysis tools for the application of innovative materials.

A Study of Cryostructuring of Polymer Systems. 54. Hybrid Organo-Inorganic Poly(vinyl alcohol) Cryogels Filled with In situ Formed Silica

Macroporous viscoelastic poly(vinyl alcohol) (PVA) cryogels are formed via the cryogenic processing (freezing/incubation in the frozen state/defrosting) of concentrated solutions of the polymer. Such materials are of significant scientific and applied interest. This also concerns various complex and composite PVA cryogels containing soluble and insoluble (fillers) additives, respectively. Novel organo-inorganic hybrid PVA cryogels containing silica components have been obtained and studied in this work. These hybrid cryogels are formed via the interaction of sodium silicate with hydrochloric acid, which are introduced into an aqueous PVA solution immediately before its cryogenic processing. As a result, the transformation of the inorganic components occurs simultaneously with the cryotropic gelation of PVA. It has been found that the physicomechanical properties, heat endurance, and macroporous morphology of the obtained samples depend on the concentration of the inorganic additives and the temperature conditions of the cryogenic process. Moreover, it has been revealed that formed NaCl and additionally polarized hydrogen bonds between OH groups of PVA and silanol groups of in situ formed poly/oligo(silicic acids) have substantial effects on the characteristics of resulting hybrid cryogels.

Hybrid cryogels composed of P(NIPAM-co-AMPS) and metal nanoparticles for rapid reduction of p-nitrophenol

Temperature-responsive macro-porous cryogels of poly(N-iospropylacryamide-co-acrylamido-2-methylpropane sulfonic acid) [P(NIPAM-co-AMPS)] were prepared through redox-initiated cryo-polymerization at −12, −18 and −24 °C. Silver or gold nanoparticles (AgNPs or AuNPs) were formed inside P(NIPAM-co-AMPS) cryogels through the thermal reduction of absorbed AgNO3 or HAuCl4, resulting in hybrid cryogels immobilized with AgNPs or AuNPs. Fourier transform infrared spectroscopy, thermal gravimetric analysis and X-ray diffraction confirmed the chemical composition. Cryogel morphology and nanoparticle distribution were investigated through scanning and transmission electron microscopies. By checking swelling ratio in neutral water, the temperature response of cryogels was identified. The hybrid cryogels were used as the catalysts to reduce p-nitrophenol with NaBH4 at different temperatures and pHs. The hybrid cryogel with AuNPs had the higher catalytic activity than the counterpart hybrid cryogel with AgNPs. The catalytic activity of hybrid cryogels increased with temperature and pH. The temperature response of cryogels facilitated their isolation from the reaction mixture. Since AuNPs were fixed tightly onto the cryogel pore-wall and hardly lost, hybrid cryogels with AuNPs demonstrated no decrease in catalytic activity for 5 cycles of p-nitrophenol reduction.

Charge‐Functionalized and Structurally Enhanced (Cryo)Hybrids from Acrylic (Co)Monomers and Kaolin: Altering Physicochemical Properties via Cryotropic Gelation

ABSTRACTThe potential to improve mechanical, structural, and mechanochemical properties of charge‐functionalized poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA)‐based hybrid cryogels is investigated. The simple and versatile synthesis of hybrid cryogels with high strength and toughness using cationic DMAEMA and ionic comonomer 2‐acrylamido‐2‐methyl‐1‐propane sulfonic acid has been proposed via in situ free‐radical crosslinking (cryo)polymerization by which the properties of virgin polymer can be modulated to required applications by incorporation of inorganic filler kaolin (KLN). Two factors affecting swelling and elasticity of hybrid gels (referred as PDA/KLNm), KLN content and gel preparation temperature, are studied. The optimum KLN concentration for desired swelling and modulus of elasticity is determined as 0.80% (w/v). Effective crosslinking density of hybrid hydrogels increases with KLN addition and this dependence is expressed by a quadratic polynomial as a function of KLN concentration. The results show that obtained hybrid gels with multiresponsive properties could be regarded as “smart materials” in sensing and actuation applications. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 1758–1778

Development of Cryogel-Based Guidance Conduit for Peripheral Nerve Regeneration.

Development of a nerve guidance conduit (NGC) is critically required for replacing the gold standard, autograft, in the repair of peripheral nerve (PN) injury with a long transecting gap. In the present study, an engineered cryogel-based NGC composed of methacrylated gelatin (MeGel), methacrylated hyaluronic acid (MeHA), and 4 arm poly(ethylene glycol) acrylate (4Arm-PEG-acrylate) was fabricated by utilizing a free radical cryopolymerization method. In vitro studies showed that the MeGel/MeHA/4Arm-PEG-acrylate hybrid cryogel provided a favorable surface and microenvironment for the adhesion, proliferation, and phenotype maintenance of rabbit Schwann cells. A 10 mm long transection in the rat sciatic nerve was created for in vivo studies. The results demonstrated that after the 16 weeks of repairing, the cryogel-based NGC supported axon regeneration and remyelination with comparable myelinating diameter and density of the regenerated nerve fibers to the autograft group. The rats with implanted cryogel-based NGC also showed sensory function recovery. This study demonstrated that our cryogel-based NGC is effective at assisting the repair of damaged PN because of its excellent structural stability, great handling convenience, and regeneration guidance capacity.

Poly(Vinyl Alcohol) Cryogels Formed from Polymer Solutions in Dimethyl Sulfoxide with Tetramethoxysilane Additives

Organic–inorganic hybrid cryogels of poly(vinyl alcohol) (PVA) containing silica inclusions (SiO2) were obtained and studied. Such inclusions were formed in the course of hydrolytic polycondensation (sol-gel process) of tetramethoxysilane (TMOS) introduced into concentrated polymer solutions in dimethyl sulfoxide (DMSO). PVA concentration in these solutions was 60, 80 or 100 g/L; while the concentration of TMOS was varied in a range of 0.15–0.61 mol/L. The polymer solutions were subjected to the cryogenic treatment at temperatures by 40 °С lower than DMSO crystallization temperature (+18.4°C). The frozen samples were thawed out at a heating rate of 0.03°/min. It is shown that moderate freezing at −21.6 °C, then frozen storage and subsequent thawing of the initial reaction mixture PVA/DMSO/TMOS/acid catalyst resulted in the formation of strong macroporous PVA/SiO2 cryogels. Such cryogel materials are hybrid systems, because the gel-forming polymer and the silica containing moieties belong to the content of the gel phase. The basis of this intermolecular interaction is hydrogen bonding between OH groups of the adjacent chains. This leads to the formation of modified microcrystallinity zones that perform as the nodes of the three-dimensional network of cryogels. The effects of significant increase in their rigidity and heat-resistance with increasing PVA and TMOS concentration in the initial feed were also observed. It was shown that the success of the synthesis of transparent elastic and heat-resistant PVA/SiO2 cryogels depends on the choice of the optimal ratio between the precursors and the combined effect of the liquid (methanol and water) and silicon-containing components on the formation of multiple hydrogen bonds and microcrystallites.

Design and molecular dynamics of multifunctional sulfonated poly(dimethylaminoethyl methacrylate)/mica hybrid cryogels through freezing-induced gelation.

This article addresses various strategies that have been explored to design sulfonated poly(dimethylaminoethyl methacrylate)/mica hybrid-gels with optimized network parameters and mechanical/swelling properties. A series of hybrid cryogels and hydrogels containing amino and sulfonic acid groups were prepared from N,N-dimethylaminoethyl methacrylate (DMAEMA) and 2-acrylamido-2-methyl-1-propane sulfonic acid in the presence of inorganic additive mica via a cryogelation process and conventional in situ copolymerization. Cryogelation was used to fine-tune the mechanical properties of the PDMAEMA-based hybrid gels. The effects of pH, temperature and mica content on the network parameters, mechanical properties and swelling behavior were discussed. X-ray diffractometry and Fourier transform infrared spectroscopy confirmed that mica particles had participated in (cryo)polymerization, and the thermal stability and surface morphologies were improved by the addition of mica. The profile of water loss, decomposition of amine groups and breakdown of PDMAEMA chains of the resulting hybrid gels were determined by thermogravimetric analysis. A critical mica concentration was found for the hybrid hydrogels where the degree of swelling attains a maximum value. Below 0.50% (w/v) of mica, the ionic nature of mica dominates its crosslinker effect. The hybrid cryogels were tough and able to recover at room temperature after compression testing. The prepared hybrid-gels showed an enhanced swelling response and on-off switching swelling characteristics in water and in aqueous NaCl solutions. The parameters of equilibrium swelling, the initial swelling rate, the diffusional exponent, and the diffusion coefficient were evaluated and the swelling kinetics of the hybrid hydrogels and cryogels in water followed the pseudo second order model. All the prepared hybrid hydrogel and cryogel materials with tunable mechanical stability and elasticity can be excellent candidates for designing smart materials.

In Situ Polyphosphate Nanoparticle Formation in Hybrid Poly(vinyl alcohol)/Karaya Gum Hydrogels: A Porous Scaffold Inducing Infiltration of Mesenchymal Stem Cells.

The preparation and characterization of a porous hybrid cryogel based on the two organic polymers, poly(vinyl alcohol) (PVA) and karaya gum (KG), into which polyphosphate (polyP) nanoparticles have been incorporated, are described. The PVA/KG cryogel is prepared by intermolecular cross‐linking of PVA via freeze‐thawing and Ca2+‐mediated ionic gelation of KG to form stable salt bridges. The incorporation of polyP as amorphous nanoparticles with Ca2+ ions (Ca‐polyP‐NP) is achieved using an in situ approach. The polyP constituent does not significantly affect the viscoelastic properties of the PVA/KG cryogel that are comparable to natural soft tissue. The exposure of the Ca‐polyP‐NP within the cryogel to medium/serum allows the formation of a biologically active polyP coacervate/protein matrix that stimulates the growth of human mesenchymal stem cells in vitro and provides the cells a suitable matrix for infiltration superior to the polyP‐free cryogel. In vivo biocompatibility studies in rats reveal that already two to four weeks after implantation into muscle, the implant regions containing the polyP‐KG/PVA material become replaced by initial granulation tissue, whereas the controls are free of any cells. It is proposed that the polyP‐KG/PVA cryogel has the potential to become a promising implant material for soft tissue engineering/repair.

Rapid thermal responsive conductive hybrid cryogels with shape memory properties, photothermal properties and pressure dependent conductivity

Stimuli responsive cryogels with multi-functionality have potential application for electrical devices, actuators, sensors and biomedical devices. However, conventional thermal sensitive poly(N-isopropylacrylamide) cryogels show slow temperature response speed and lack of multi-functionality, which greatly limit their practical application. Herein we present conductive fast (2 min for both deswelling and reswelling behavior) thermally responsive poly(N-isopropylacrylamide) cryogels with rapid shape memory properties (3 s for shape recovery), near-infrared (NIR) light sensitivity and pressure dependent conductivity, and further demonstrated their applications as temperature sensitive on-off switch, NIR light sensitive on-off switch, water triggered shape memory on-off switch and pressure dependent device. These cryogels were first prepared in dimethyl sulfoxide below its melting temperature in ice bath and subsequently put into aniline or pyrrole solution to in situ deposition of conducting polyaniline or polypyrrole nanoparticles. The continuous macroporous sponge-like structure provides cryogels with rapid responsivity both in deswelling, reswelling kinetics and good elasticity. After incorporating electrically conductive polyaniline or polypyrrole nanoaggregates, the hybrid cryogels exhibit desirable conductivity, photothermal property, pressure dependent conductivity and good cytocompatibility. These multifunctional hybrid cryogels make them great potential as stimuli responsive electrical device, tissue engineering scaffolds, drug delivery vehicle and electronic skin.

Biopolymers/poly(ε-caprolactone)/polyethylenimine functionalized nano-hydroxyapatite hybrid cryogel: Synthesis, characterization and application in gene delivery

Nano-hydroxyapatite (nHAp), surface functionalized with linear polyethylenimine (LPEI), was used for the preparation of biocomposites in combination with biopolymers and poly(ε-caprolactone) (PCL), by cryogelation technique, to yield biomimetic scaffolds with controlled interconnected macroporosity, mechanical stability, and predictable degradation behavior. The structural characteristics, swelling and degradation behavior of hydroxyapatite and hydroxyapatite/β-tricalcium phosphate (β-TCP) filled matrices were investigated as compared to the corresponding naked polymer 3D system. It was found that the homogeneity and cohesivity of the composite are significantly dependent on the size and amount of the included inorganic particles, which are thus determining the structural parameters. Surface modification with LPEI and nanodimensions favored the nHAp integration in the organic matrix, with preferential location along protein fibers, while β-TCP microparticles induced an increased disorder in the hybrid system. The biocomposite including nHAp only was further investigated targeting biomedical uses, and proved to be non-cytotoxic and capable of acting as gene-activated matrix (GAM). It allowed sustained delivery over time (until 22days) of embedded PEI25-pDNA polyplexes at high levels of transgene expression, while insuring a decrease in cytotoxicity as compared to polyplexes alone. Experimental data recommend such biocomposite as an attractive material for regenerative medicine.

Alleviating liver failure conditions using an integrated hybrid cryogel based cellular bioreactor as a bioartificial liver support

Conventionally, some bioartificial liver devices are used with separate plasmapheresis unit to separate out plasma from whole blood and adsorbent column to detoxify plasma before it passes through a hepatocytes-laden bioreactor. We aim to develop a hybrid bioreactor that integrates the separate modules in one compact design improving the efficacy of the cryogel based bioreactor as a bioartificial liver support. A plasma separation membrane and an activated carbon cloth are placed over a HepG2-loaded cryogel scaffold in a three-chambered bioreactor design. This bioreactor is consequently connected extracorporeally to a rat model of acute liver failure for 3 h and major biochemical parameters studied. Bilirubin and aspartate transaminase showed a percentage decrease of 20–60% in the integrated bioreactor as opposed to 5–15% in the conventional setup. Urea and ammonia levels which showed negligible change in the conventional setup increase (40%) and decrease (18%), respectively in the integrated system. Also, an overall increase of 5% in human albumin in rat plasma indicated bioreactor functionality in terms of synthetic functions. These results were corroborated by offline evaluation of patient plasma. Hence, integrating the plasmapheresis and adsorbent units with the bioreactor module in one compact design improves the efficacy of the bioartificial liver device.

A reusable surface-quaternized nanocellulose-based hybrid cryogel loaded with N-doped TiO2for self-integrated adsorption/photo-degradation of methyl orange dye

Self-integrated adsorption/photo-degradation of methyl orange dye.

Hybrid Alginate‐Based Cryogels for Life Science Applications

AbstractThis work presents a novel route toward porous scaffolds for tissue engineering and regenerative medicine (TERM) applications. Hybrid cryogels with gelatin, gellan gum, carboxymethylcellulose, and lignin were prepared by a two‐step process. Textural properties of the cryogels were analyzed by SEM and micro‐computed tomography. The results indicated that rapid freezing retained sample shape and yielded macroporous materials. The mechanical properties of the cryogels were characterized in compression mode. Cytotoxicity studies indicated that the hybrid‐alginate cryogels did not present cytotoxicity and have the potential to be used in TERM.

Highly Flexible and Resilient Elastin Hybrid Cryogels with Shape Memory, Injectability, Conductivity, and Magnetic Responsive Properties.

A strategy utilizing elastin peptide macroporous cryogels to build highly flexible scaffolds to load carbon nanotubes, polypyrrole, and iron oxide magnetic nanoparticles, is presented. This combines high elasticity, flexibility, shape memory property, and injectable property together with conductivity and/or magnetic responsive property. The network can afford 97.5% compressive strain with an excellent conductivity of 50.1 ± 2.9 S cm(-1) at 90% strain.

Preparation and characterization of modified nanosilica/PNIPAm hybrid cryogels

A series of macroporous hybrid cryogels based on poly(N-isopropylacrylamide) (PNIPAm) were synthesized by free radical polymerization in the presence of organically modified nanosilica. To improve the interaction of silica nanoparticles with polymer structure, the silica surface was first treated with 3-methacryloxypropyltrimethoxysilane (MPTMS). Then a series of hybrid cryogels each containing 1 wt.% nanosilica and various amounts of MPTMS (1–4 wt.% to monomer NIPAm) were prepared. The yield of methacrylate modification of the nanosilica surface determined by TGA analysis was 11.2 wt.%. The particle size distribution of modified nanosilica particles was investigated by dynamic light scattering technique (DLS) and the mean particle diameter with respect to number was found as 68 nm. The morphology of cryogels was evaluated by SEM. The improvement in the thermal and mechanical properties using the addition of modified silica nanoparticles was achieved.

Modulating SWCNT–silica interactions for enhanced dispersibility and hybrid cryogel formation

Single walled carbon nanotubes (SWCNTs) form a special class of carbon materials with high electric and thermal conductivity. Ordinary SWCNTs exist in the form of bundles, primarily because of intertubular van der Waals attraction. Here we show that silica nanoparticles (NPs) with tunable surface energy can be used as efficient aqueous dispersant for SWCNTs. A subsequent controlled solvent-evaporation leads to the formation of SWCNT–silica hybrid cryogels. We characterize cryogels using gas/vapor adsorption and electric conductivity measurements and show that their porosity and conductivity can be fine-tuned by altering the silica-to-SWCNT relative concentration. We believe that the SWCNT–silica hybrid cryogels can be used as a precursor for fabricating functional electrodes for advanced energy storage devices.

Investigation of lysozyme adsorption performance of Cu2+-attached PHEMA beads embedded cryogel membranes

For the purification of large molecules, cryogels are an alternative stationary phase to particle based media. But, due to the drawbacks of cryogels (i.e., low surface area) and particle sorbents (i.e., pressure drop in fixed beds), in recent years, the use of hybrid cryogels has greatly increased. In this study, a novel hybrid cryogel column was synthesized for the purification of lysozyme from aqueous solutions and hen egg white (HEW). Firstly, poly(2-hydroxyethyl methacrylate) beads (2μm size) were prepared, and after iminodiacetic acid (IDA) immobilization, Cu2+ ions were attached via the IDA chelating groups. These arranged Cu2+-attached PHEMA beads (Cu2+-ABs) were located into PHEMA based cryogel in order to prepare Cu2+-ABs embedded supermacroporous hybrid cryogel (Cu2+-ABsEHC) column. The specific surface area of the hybrid cryogel was found as 95m2/g by using BET. The amount of IDA on beads was found as 875μmol IDA/g. It was approached to the optimum adsorption levels at initial lysozyme concentration of 4mg/mL and pH8.0 as 874.9mg/g beads. The purity of lysozyme adsorbed from HEW was studied by SDS-PAGE with a purity of 86.4%. It is demonstrated that this column is a potential separation medium for purification of lysozyme from HEW.

Macroporous structures based on biodegradable polymers—candidates for biomedical application

New hybrid cryogels comprising natural polymers (free atelocollagen or atelocollagen mixed with a hyaluronic acid derivative) and a synthetic polyester--poly(ε-caprolactone)--were successfully developed by a cryogenic treatment and a subsequent freeze-drying step. Systematic studies on the effect of preparation conditions (reaction mixture composition, total concentration of the feed dispersion, and freezing regime) on cryogelation efficiency were conducted. The degree of cross-linking and the morphology of the obtained materials were analyzed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and (environmental) scanning electron microscopy (ESEM/SEM) techniques. Considering their possible biomedical application, the developed macroporous hydrogels were also investigated in terms of swelling behavior and hemo/biocompatibility. The produced hydrogels had an uniform interconnected open porous structure with a porosity of up to 95% and pores size in the range of 83-260 μm. All obtained cryogels were elastic, mechanically stable, with a superfast swelling kinetics. In vitro hemocompatibility assay gave hemolysis ratios (HRs) lower than 0.5%, which is below the permissible limit of 5%. The in vivo tolerance tests performed by implantation of cryogel specimens into Wistar rats proved their biocompatibility.

Tunable hybrid cryogels functionalized with microparticles as supermacroporous multifunctional biomaterial scaffolds

This study aims at incorporating microparticles (MPs) into polymeric network of cryogels to fabricate a multifunctional biomaterial scaffold (cryogel-microparticle [C-MP] composite) which has microstructured biocompatible pore surface, supermacroporous interconnected pore distribution and capability to simultaneously deliver bioactive molecules. Three types of MPs (i.e. poly(D,L-lactide-co-glycolide), chitosan, and silica MPs) were separately incorporated in three different cryogels (i.e. chitosan–agarose, chitosan–agarose–gelatin, and chitosan–gelatin), demonstrating the generality of the approach. Factors affecting distribution of MPs within the cryogel were investigated to achieve uniform distribution of MPs within the pore wall of cryogel as well as the whole cryogel monolith to create microstructured pore surface of C-MP composites, which was characterized by scanning electron microscopy, fluorescence microscopy, infrared spectral analysis (FTIR), and water uptake properties. Further, mouse embryonic fibroblasts (NIH 3T3), mouse myoblasts (C2C12), and human lung cancer cells (NCI-H460) were grown on microstructured C-MP composites and nonstructured cryogels to check adherence and growth of cells, and investigate their biocompatibility. To test the potential of C-MP composites for delivery of bioactive/drug molecules to cells growing in three-dimensional (3D) conditions, doxorubicin-loaded silica MP-chitosan–gelatin C-MP composites were fabricated and anti-proliferative effect of doxorubicin was observed on growing human cervical cancer cells (HeLa).

Hierarchically Macroporous Cryogels of Polyisobutylene and Silica Nanoparticles

Organic-inorganic hybrid materials attract particular interest because of their excellent mechanical properties. Here, we report the synthesis of hybrid cryogels consisting of interpenetrated polyisobutylene and silica networks. The gels were prepared by cross-linking of butyl rubber in cyclohexane containing silica nanoparticles using sulfur monochloride (S(2)Cl(2)) as a cross-linking agent. The microstructure of the hybrid networks formed at subzero temperatures exhibits two generations of pores: 10(1) microm sized large pores due to the cyclohexane crystals acting as a template during gelation and, 10(-1)-10(0) microm sized small pores between the aggregates of the nanoparticles. The nanoparticles in hybrid cryogels accumulate within the large pores where cyclohexane crystals originally resided. Compared to the organogel networks with an elastic modulus of a few kPa, hybrid networks exhibit a modulus of elasticity around 300 kPa. Hybrid cryogels can be converted into organic cryogels by dissolving the silica component in aqueous hydrofluoric acid, while removing the polymer component by calcination results in porous silica networks with 10(-1) microm sized pores.