Core-shell Hydrogel Research Articles

Preparation of 3D Zonal and Interactional Glomerular Models Based on Composite Core–Shell Hydrogel Microspheres

Preparation of 3D Zonal and Interactional Glomerular Models Based on Composite Core–Shell Hydrogel Microspheres

Assembly and jamming of polar additive-swollen microgels at liquid–liquid interfaces: From inverse Pickering emulsions to functional materials

HypothesisPoly-N-isopropylacrylamide (PNIPAM)-based microgels have garnered significant interest as effective soft particulate stabilizers because of their deformability and functionality. However, the inherent hydrophilic nature of microgel restricts their potential use in stabilizing water-in-oil (W/O) Pickering emulsions. Employing diverse polar additives can improve the hydrophobicity of microgels, thus unlocking new possibilities in inverse Pickering emulsion formation and materials fabrication. ExperimentsDifferent types of microgels were generated using free-radical precipitation polymerization with tailored physiochemical properties. The effect of various polar additives on the wettability, adsorption kinetics, and interfacial coverage of microgels was systematically investigated. Additive-swollen microgels were utilized to stabilize inverse W/O Pickering emulsions, which served as templates to develop functional materials with stimuli responsiveness and hierarchical structures. FindingsAdditive-swollen PNIPAM-based microgels exhibited enhanced hydrophobicity and superior emulsifying capability, which spontaneously assembled and jammed at oil–water interfaces, resulting in a significant interfacial energy decrease. The microgels formed a tightly packed, elastic, and responsive microgel monolayer. The feasibility of the strategy was verified by preparing various inverse W/O Pickering emulsions and high internal phase Pickering emulsions (HIPPEs). More importantly, this straightforward formation strategy of microgel-stabilized inverse W/O Pickering emulsions offered a novel platform to create functional materials with customized inner structures from microscale (e.g., responsive core–shell hydrogel microspheres and colloidosomes) to macroscale (e.g., hierarchical porous materials) that can be used for potential applications, such as recyclable contaminant removal and droplet manipulation.

Effect of inulin on structural, physicochemical, and in vitro gastrointestinal tract release properties of core-shell hydrogel beads as a delivery system for vitamin B12

In this study, core-shell hydrogel beads were developed as a controlled-release delivery system for vitamin B12. Vitamin B12-loaded microgels (MG) were prepared using gellan gum (GG). Core-shell hydrogel beads were produced by incorporating MG into pea protein isolate (PPI) and sodium alginate (AL) matrix filled/coated with different concentrations (0 %, 1 %, 3 %, 5 %, and 10 %) of inulin (IN). Based on XRD analysis, MG was successfully incorporated into core-shell hydrogel beads. In FE-SEM and FT-IR analyses, the smoother surface and denser structure of the beads were observed as IN concentration increased due to hydrogen bonds between IN and the beads. The encapsulation efficiency increased from 68.64 % to 82.36 % as IN concentration increased from 0 % to 10 %, respectively. After exposure to simulated oral and gastric conditions, core-shell hydrogel beads exhibited a lower cumulative release than MG, and a more sustained release was observed as IN concentration increased in simulated intestinal conditions.

Novel biopolymeric chitosan-urea-based core-shell hydrogel for use in sustainable agriculture

Agricultural sustainability is a major issue in recent times, deficiency of water as well as insufficient fertilizer to the crop is a main reason for it. This work is focused on core-shell hydrogel aiming to overcome the agricultural issues of water as well as deficiency of fertilizer to the plant. The core-shell hydrogel was prepared by incorporating urea in κ-carrageenan to be part of the controlled release mechanism of the core of the hydrogel. Chitosan was used for the shell structure to prepare over the core and cross-linked by the cations of the salts. The prepared hydrogel was termed as Chitosan-κ-carrageenan-Urea (CK-CU). Four different types of hydrogels were prepared with the different compositions named as CK-CU 2, CK-CU 5, CK-CU 7.5 and CK-CU 10 as varying with the ratio of 2 %, 5 %, 7.5 % and 10 % of urea respectively. The core-shell morphology structure was verified with Scanning electron microscopy (SEM) in which the complete coverage of the κ-carrageenan core by a consistent chitosan shell has been verified. Fourier transform infrared spectroscopy (FTIR) was utilized to confirm the composition of the hydrogel. Thermo-gravimetric analysis (TGA) was also performed for checking the thermal endurance of the hydrogel. The release rate of the urea was determined under Ultraviolet Visible spectroscopy. The swelling index, dewatering, and urea release rate of optimized CK-CU 10 hydrogel were found to 121 %, 21.22 %, and 70.4 % respectively. The developed Core-Shell hydrogel exhibits significant promise as a vehicle for fertilizer and as a soil conditioner in agricultural applications especially in arid and semi-arid areas.

Dual-network hydrogel capsules for controlled molecular transport via pH and temperature responsiveness

We have developed innovative core–shell hydrogel capsules with a dual-network shell structure designed for precise control of molecular transport in response to external stimuli such as pH and temperature. The capsules were fabricated using a combination of microfluidic electrospray techniques and water-in-water (w/w) core–shell droplets templating. The primary network of the shell, calcium alginate (Ca-Alg), with a pKa around 3.4, exhibits sensitivity to pH. The secondary network of the shell, poly(ethylene glycol) methyl ether methacrylate (PEGMA), undergoes a volume phase transition near 60 °C. These properties enable precise molecular transport control in/out of the capsules by modulating the surface charges through varying pH and modifying pore size through temperature changes. Moreover, the dual-network shell structure not only significantly enhances the mechanical strength of the capsules but also improves their stability under external stimulus, ensuring structural integrity during the transport of molecules. This research lays the groundwork for further investigations into the multimodal stimuli-responsive hydrogel systems to control molecular transport, important in applications such as sensors and reactors for chemical cascade reactions.

Sustainable and Robust Cellulose‐Based Core–Shell Hydrogels Recycled from Waste Cotton Fabrics as High‐Performance Food Coolants

AbstractIdeal temperature condition is one of the essential determinants that critically impact the quality of food products. Conventional water‐based ice cubes present challenges from meltwater being breeding grounds for microorganisms and heightening the risk for cross‐contamination. Hereby, the presented cellulose‐based hydrogels crosslinked by epichlorohydrin are dip‐coated with alginate/calcium chloride to form a core–shell structure for achieving the critical benchmarks of an ideal food coolant with limited meltwater production, high‐water retention capacity, and high mechanical strength. The structures and properties of the hydrogels before and after freeze–thaw cycles are characterized by scanning electron microscopy, compressive test, water retention test, and differential scanning calorimetry. All formulated hydrogels demonstrate promising compressive strength, latent heat of fusion, and water retention properties. Notably, the C2A10Cl hydrogel exhibits a maximum compressive strength of 144.7 kPa and high latent heat of fusion of 272.5 J g–1, which is better than previously reported sustainable hydrogel coolants. Furthermore, comparison studies reveal that the cellulose‐based hydrogels demonstrate a similar thawing pattern to conventional ice cubes but without the generation of any meltwater. The temperature of blueberries can be cooled down from 22 to 3.9 °C in 32 min by the hydrogels and in 26 min by ice cubes, respectively.

3D hydrogel microfibers promote the differentiation of encapsulated neural stem cells and facilitate neuron protection and axon regrowth after complete transactional spinal cord injury

Spinal cord injury (SCI) can cause permanent impairment to motor or sensory functions. Pre-cultured neural stem cell (NSC) hydrogel scaffolds have emerged as a promising approach to treat SCI by promoting anti-inflammatory effects, axon regrowth, and motor function restoration. Here, in this study, we performed a coaxial extrusion process to fabricate a core-shell hydrogel microfiber with high NSC density in the core portion. Oxidized hyaluronic acid, carboxymethyl chitosan, and matrigel blend were used as a matrix for NSC growth and to facilitate the fabrication process. During the in vitro differentiation culture, it was found that NSC microfibers could differentiate into neurons and astrocytes with higher efficiency compared to NSC cultured in petri dishes. Furthermore, during in vivo transplantation, NSC microfibers were coated with polylactic acid nanosheets by electrospinning for reinforcement. The coated NSC nanofibers exhibited higher anti-inflammatory effect and lesion cavity filling rate compared with the control group. Meanwhile, more neuron- and oligodendrocyte-like cells were visualized at the lesion epicenter. Finally, axon regrowth across the whole lesion site was observed, demonstrating that the microfiber could guide renascent axon regrowth. Experiment results indicate that the NSC microfiber is a promising bioactive treatment for complete SCI treatment with superior outcomes.

A Stable and Sensitive Engineering Bacterial Sensor via Physical Biocontainment and Two-Stage Signal Amplification.

Although engineering bacterial sensors have outstanding advantages in reflecting the actual bioavailability and continuous monitoring of pollutants, the potential escape risk of engineering microorganisms and lower detection sensitivity have always been one of the biggest challenges limiting their wider application. In this study, a core-shell hydrogel bead with functionalized silica as the core and alginate-polyacrylamide as the shell have been developed not only to realize zero escape of engineered bacteria but also to maintain cell activity in harsh environments, such as extremely acidic/alkaline pH, high salt concentration, and strong pressure. Particularly, after combining the selective preconcentration toward pollutants by functionalized core and the positive feedback signal amplification of engineering bacteria, biosensors have realized two-stage signal amplification, significantly improving the detection sensitivity and reducing the detection limit. In addition, this strategy was actually applied to the detection of As(III) and As(V) coexisting in environmental samples, and the detection sensitivity was increased by 3.23 and 4.39 times compared to sensors without signal amplification strategy, respectively, and the detection limits were as low as 0.39 and 0.86 ppb, respectively.

Investigation of swelling behaviour monolayer and double Layer polysaccharide based composite hydrogels

ABSTRACT In this study, monolayer and double layer (core-shell) composite hydrogel beads with and without hydroxyapatite which have potential applications in drug delivery systems were synthesized, and their swelling behaviours were investigated in different pH mediums. The composite hydrogel beads was prepared by crosslinking sodium alginate and kappa-carrageenan (by using Ca+2 and K+1). Core-shell hydrogel beads were formed by coating monolayer composite hydrogel beads with the mixture of sodium alginate and kappa-carrageenan. The structure of hydrogel beads was characterized by Fourier Transform Infrared Spectrophotometer, Scanning Electron Microscopy and Differential Scanning Calorimetry. The effects of the composite hydrogel beads combination and the concentration of crosslinker on swelling behaviours were investigated. Swelling kinetics data were tested using pseudo-second-order model, and the pseudo-second-order model is estimated as a convenient model to represent the swelling kinetic. The results indicated that swelling behaviours of hydrogel beads changed with composite hydrogel beads combination and concentration of crosslinker.

Fabrication of Core-Shell Hydrogel Bead Based on Sodium Alginate and Chitosan for Methylene Blue Adsorption

Fabrication of Core-Shell Hydrogel Bead Based on Sodium Alginate and Chitosan for Methylene Blue Adsorption

Improving the thermal stability of phytase using core-shell hydrogel beads

A core–shell hydrogel bead system was designed to maintain the catalytic activity of phytase and protect its enzymatic functionality from heat treatment. The designed structure consists of a chitosan-phytase complex core and an alginate-carrageenan hydrogel shell. The core–shell hydrogel was optimized to improve phytase encapsulation efficiency and increase the thermal stability of the encapsulated phytase. After heat treatment, encapsulated phytase retained ∼ 70 % of its catalytic activity and the same secondary structure of free phytase. Fourier transform infrared spectroscopy indicated strong intermolecular interactions between chitosan and phytase in the core, but little interaction between the core and the alginate and κ-carrageenan shell, this supports the structural and functional stability of the phytase. Differential scanning calorimetry confirmed that the designed core–shell structure had a higher melting point. Encapsulating phytase in a core–shell hydrogel bead can enhance the thermal stability of phytase, which broadens the potential applications for phytase delivery.

New Poly(lactic acid)-Hydrogel Core-Shell Scaffolds Highly Support MSCs' Viability, Proliferation and Osteogenic Differentiation.

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin-chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core-shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Scaffolds with a higher core/shell ratio exhibit higher mechanical properties, whereas reducing the core/shell ratio results in higher values of bioactive hydrogel content. Hydrogel contents up to 25 wt% could be achieved while maintaining high compression stiffness (>200 MPa) and strength (>5 MPa), overall, within the range of values displayed by human bone tissue. In addition, mechanical properties remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core-shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core-shell scaffolds are biocompatible, and their physical-mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core-shell scaffolds can be considered and further studied, in view of clinically relevant endpoints in bone regenerative medicine.

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery (Adv. Healthcare Mater. 31/2023)

Orthogonal Gelations to Synthesize Core–Shell Hydrogels Loaded with Nanoemulsion‐Templated Drug Nanoparticles for Versatile Oral Drug Delivery (Adv. Healthcare Mater. 31/2023)

Preparation of pH-sensitive alginate-based hydrogel by microfluidic technology for intestinal targeting drug delivery

Hydrogel microspheres stand out in drug delivery due to their small particle size, biocompatibility and good internal stability. In this paper, pH-sensitive hydrogels are prepared by microfluidic technology for targeted drug delivery in the small intestine. A coaxial dual-channel microfluidic chip is constructed. By analyzing the effects of flow rates and three fracture stages (Rayleigh-Plateau instability crushing stage, pressure difference crushing stage and shear force crushing stage) on the size of hydrogel microspheres, the optimal control stage of the microsphere size is determined (shear force crushing stage). Based on this, the accurate control model of the hydrogel microsphere size is proposed. In addition, based on the coaxial dual channel microfluidic chip, a monolayer hydrogel microcapsule loaded with Indometacin is prepared. The core-shell hydrogel microcapsules loaded with Indometacin are prepared by an improved coaxial three channel microfluidic chip. The swelling rates of both microcapsules in simulated intestinal fluid are significantly higher than those in simulated gastric fluid. The results of in vitro simulated release experiments show that the two hydrogel microcapsules basically do not release in simulated gastric juice. In simulated intestinal fluid, single-layer hydrogel microcapsules show rapid release, while core-shell hydrogel microcapsules showed slow release. In conclusion, the alginate-based hydrogel microcapsules have good stability and pH sensitivity, and are suitable for targeted drug delivery in the small intestine.

Fabrication of core–shell beads, hollow capsules, and AuNP-embedded catalytic beads from an ultrasmall peptide hydrogel

Hydrogel beads have emerged as a new class of soft materials that infuse the noble properties of macro-dimensional hydrogels in tiny, easily operable, and robust droplets. Usually, polymeric hydrogels are used in the production of hydrogel beads due to their high structural rigidity and durability, and low molecular weight hydrogel beads are relatively uncommon. Herein, we employed an ultra-short peptide (Pyrene-Lys-Cys, PyKC) based low molecular weight injectable hydrogel, that remains insoluble in bulk solvents, to create stable hydrogel beads using a simple extrusion technique. To enhance durability and applicability, the beads are coated with a polymeric shell, resulting in a core–shell configuration. The shell of the core–shell beads can be modified through a variety of organic conjugation reactions. Also, the core (hydrogel) can be sacrificed using DMSO, resulting in the formation of hollow organic capsules. Furthermore, the core–shell beads enabled the in-situ synthesis and stabilization of gold nanoparticles on the bead surface. The gold-loaded beads demonstrated remarkable catalytic efficiency in the reduction of p-nitrophenol and hazardous azo dyes. In a nutshell, the extremely modular and customizable nature of the PyKC-based core–shell hydrogel bead may allow it to function as a unified platform for multifaceted applications.

Mangiferin loaded carrageenan/chitosan core-shell hydrogel beads: Preparation, characterization and proposed application

In this work, an investigation on the use of mangiferin, a bioactive compound, in a controlled release hydrogel system was carried out. Mangiferin isolated from mango leave waste was tested for its antibacterial activities by disc diffusion, agar well and agar dilution methods. The results confirmed effective antibacterial effects against Vibrio parahaemolyticus and Vibrio cholerae, the common species found in fresh seafood that can cause acute diarrheal illness. However, application of this polyphenolic natural compound is limited by its poor water solubility resulting in low bioavailability. To overcome is limitation, biopolymeric core-shell hydrogel beads incorporated with mangiferin were fabricated by a one-step gelling method. The core particles loaded with mangiferin were prepared from κ-carrageenan solution which were subsequently ionic-crosslinked and encapsulated with the chitosan shells. The formation of core-shell morphology was verified by light microscope observation and confirmed that the κ-carrageenan core was completely covered with the uniform shell of chitosan. The composition of microsphere beads was also examined with Fourier transform infrared spectroscopy and scanning electron microscopy equipped with energy dispersive X-ray analysis. The core-shell hydrogel was able to encapsulate mangiferin with the optimum loading efficiency of 85%. The release kinetics was evaluated at different temperatures and Korsmeyer-Peppas was the most appropriate model to represent the release profiles of mangiferin from hydrogel beads. Biocompatibility test performed on all of the hydrogel samples exhibited a good viability for the L929 and Vero cells with low cytotoxicity. Investigations on the microsphere hydrogels revealed that they could regulate the release of bioactive mangiferin and possessed promising potential to be utilized for quality protection of fresh seafood.

Orthogonal Gelations to Synthesize Core-Shell Hydrogels Loaded with Nanoemulsion-Templated Drug Nanoparticles for Versatile Oral Drug Delivery.

Hydrophobic active pharmaceutical ingredients (APIs) are ubiquitous in the drug development pipeline, but their poor bioavailability often prevents their translation into drug products. Industrial processes to formulate hydrophobic APIs are expensive, difficult to optimize, and not flexible enough to incorporate customizable drug release profiles into drug products. Here, a novel, dual-responsive gelation process that exploits orthogonal thermo-responsive and ion-responsive gelations is introduced. This one-step "dual gelation" synthesizes core-shell (methylcellulose-alginate) hydrogel particles and encapsulates drug-laden nanoemulsions in the hydrogel matrices. In situ crystallization templates drug nanocrystals inside the polymeric core, while a kinetically stable amorphous solid dispersion is templated in the shell. Drug release is explored as a function of particle geometry, and programmable release is demonstrated for various therapeutic applications including delayed pulsatile release and sequential release of a model fixed-dose combination drug product of ibuprofen and fenofibrate. Independent control over drug loading between the shell and the core is demonstrated. This formulation approach is shown to be a flexible process to develop drug products with biocompatible materials, facile synthesis, and precise drug release performance. This work suggests and applies a novel method to leverage orthogonal gel chemistries to generate functional core-shell hydrogel particles.

Fabrication and Cell Culture Applications of Core-Shell Hydrogel Fibers Composed of Chitosan/DNA Interfacial Polyelectrolyte Complexation and Calcium Alginate: Straight and Beaded Core Variations.

Core-shell hydrogel fibers are widely used in cell culture applications. A simple and rapid method is presented for fabricating core-shell hydrogel fibers, consisting of straight or beaded core fibers, for cell culture applications. The core fibers are prepared using interfacial polyelectrolyte complexation (IPC) with chitosan and DNA. Briefly, two droplets of chitosan and DNA are brought in contact to form an IPC film, which is dragged to prepare an IPC fiber. The incubation time and DNA concentration are adjusted to prepare straight and beaded IPC fibers. The fibers with Ca2+ are immersed in an alginate solution to form calcium alginate shell hydrogels around the core IPC fibers. To the best of the knowledge, this is the first report of core-shell hydrogel fibers with IPC fiber cores. To demonstrate cell culture, straight hydrogel fibers are applied to fabricate hepatic models consisting of HepG2 and 3T3 fibroblasts, and vascular models consisting of human umbilical vein endothelial cells and 3T3 fibroblasts. To evaluate the effect of co-culture, albumin secretion, and angiogenesis are evaluated. Beaded hydrogel fibers are used to fabricate many size-controlled spheroids for fiber and cloning applications. This method can be widely applied in tissue engineering and cell analysis.

Stability of the Arginine-Ornithine-Citrulline Cycle Maintained by Tumor-Stroma Interactions in Cell Coculture Hydrogel Microspheres.

Tumor-stroma interaction is the core process of tumor metastasis. Therefore, building a model of tumor-stromal cell communication is crucial for understanding the tumor metastasis process and curing cancer completely. In this research, a controllable three-dimensional (3D) tumor-stroma coculture microsphere model based on droplet microfluidic technology was developed to culture human lung cancer cells (A549 cell) and fibroblast cells (NIH-3T3 cell) using core-shell hydrogel microspheres to partition different kinds of cells. In our coculture model, tumor cells show a trend of epithelial-mesenchymal transition (EMT): a decrease in the number of surface E-cadherin and an increase in the number of N-cadherin. At the same time, fibroblasts are activated into cancer-associated fibroblasts (CAFs) as the level of interleukin-6 (IL-6) released is increased. In addition, an interesting phenomenon was discovered; in the absence of fibroblasts, the metabolism of the tumor cell culture alone leads to arginine depletion and citrulline accumulation, whereas a coculture can maintain the arginine-ornithine-citrulline cycle to reach equilibrium after 72 h, and the balance increases the stress resistance of tumor cells. This discovery may provide a new direction for understanding tumor resistance.

Oral Delivery of Bioactive Glass-Loaded Core-Shell Hydrogel Microspheres for Effective Treatment of Inflammatory Bowel Disease.

Resolving inflammation and promoting intestinal tissue regeneration are critical for inflammatory bowel disease (IBD) treatment. Bioactive glass (BG) is a clinically approved bone graft material and has been shown to modulate inflammatory response, but it is unknown whether BG can be applied to treat IBD. Here, it is reported that BG attenuates pro-inflammatory response of lipopolysaccharide (LPS)-stimulated macrophages and hence reduces inflammatory damage to intestinal organoids in vitro. In addition, zein/sodium alginate-based core-shell microspheres (Zein/SA/BG) are developed for oral delivery of BG, which helps prevent premature dissolution of BG in the stomach. The results show that Zein/SA/BG protects BG from a gastric-simulated environment while dissolved in an intestinal-simulated environment. When administered to acute and chronic colitis mice model, Zein/SA/BG significantly reduces intestinal inflammation, promotes epithelial tissue regeneration, and partially restores microbiota homeostasis. These findings are the first to reveal the therapeutic efficacy of BG against IBD, which may provide a new therapeutic approach at low cost for effective IBD treatment.