Hydrogel Capsules Research Articles

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.

Understanding the column and batch adsorption mechanism of pesticide 2,4,5-T utilizing alginate-biomass hydrogel capsule: A computational and economic investigation

Water pollution has remained a pressing concern in recent years, presenting multifaceted challenges in search of effective mitigation strategies. Our study, which targets mitigating pollution caused by 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a significant aquatic pollutant, is innovative in its approach. We have identified adsorption as a promising, cost-effective method for its removal. Our research strategy involves dynamic adsorption utilizing a peristaltic pump and composite beads containing activated carbon and sodium alginate (CA/Alg), a novel combination that mimics industrial processes. To optimize column adsorption, we examine bead stability under varied pH conditions and optimize parameters such as concentration, adsorption time, and pH through batch adsorption experiments, employing experimental design techniques. Additionally, we optimize column adsorption factors, including bead height, circulation time, and flow rate, crucial for process efficiency, and under these optimum conditions (C2,4,5-T = 80 ppm. pH = 2, t = 27h30min, H = 30 cm and D = 0.5 mL/min) the capacity of adsorption equal to 748.25 mg/g. Characterization techniques like SEM, EDX, BET analysis, XRD, and FTIR provide insights into the morphology, composition, surface area (331 m2/g), pore volume (0.11 cm3/g), crystal structure, and functional groups of the CA-P/Alg adsorbent. Theoretical analysis elucidates the adsorption mechanism and interaction with pollutants. Economic analysis, encompassing CAPEX and OPEX estimation, evaluates the feasibility of implementing this cleanup method at an industrial scale, considering initial investment and ongoing operational costs, indicating potential savings of 64 % compared with the activated carbon normally used on the Moroccan market. This comprehensive and innovative approach addresses water pollution challenges effectively while ensuring economic viability for industry-scale implementation.

Hydrogel capsules as new delivery system for Trichoderma koningiopsis Th003 to control Rhizoctonia solani in rice (Oryza sativa)

The incorporation of biological control agents (BCAs) such as Trichoderma spp. in agricultural systems favors the transition towards sustainable practices of plant nutrition and diseases control. Novel bioproducts for crop management are called to guarantee sustainable antagonism activity of BCAs and increase the acceptance of the farmers. The encapsulation in polymeric matrices play a prominent role for providing an effective carrier/protector and long-lasting bioproduct. This research aimed to study the influence of biopolymer in hydrogel capsules on survival and shelf-life of T. koningiopsis. Thus, two hydrogel capsules prototypes based on alginate (P1) and amidated pectin (P2), containing conidia of T. koningiopsis Th003 were formulated. Capsules were prepared by the ionic gelation method and calcium gluconate as crosslinker. Conidia releasing under different pH values of the medium, survival of conidia in drying capsules, storage stability, and biocontrol activity against rice sheath blight (Rhizoctonia solani) were studied. P2 prototype provided up to 98% survival to Th003 in fluid bed drying, faster conidia releasing at pH 5.8, storage stability greater than 6 months at 18 °C, and up to 67% of disease reduction. However, both biopolymers facilitate the antagonistic activity against R. solani, and therefore can be incorporated in novel hydrogel capsules-based biopreparations. This work incites to develop novel biopesticides-based formulations with potential to improve the delivery process in the target site and the protection of the active ingredient from the environmental factors.

Rapid coating of millimeter‐scale hydrogel capsules with interfacial polymerization

AbstractA rapid and mild coating strategy was applied on the millimeter scale calcium alginate capsules (Ca‐SA caps) by in situ interfacial polymerization of ethyl cyanoacrylate (ECA). The generated poly(ethyl cyanoacrylate) (PECA) coating was initiated by trace water in the surface of the Ca‐SA caps. The effects of ECA content, reaction time, and type of aromatic solvent on the morphology and control‐release property of the resulting PECA‐coated Ca‐SA caps (Ca‐SA caps@PECA) were investigated. The results demonstrated a white PECA layer successfully coated on the surface of Ca‐SA caps. Notably, the Ca‐SA caps@PECA remained consistently pleasing spherical shape as prepared in methylbenzene and ethylbenzene. When the ECA was 6 mL, the thickness of PECA layer of the Ca‐SA caps@PECA was 43.52 μm. Compared with the Ca‐SA caps, the weight retention ratio of water in the Ca‐SA caps@PECA increased by 254.61%, indicating the effective delay of water diffusion from core of the Ca‐SA caps@PECA. Moreover, the PECA coating improved the stability of the Ca‐SA caps@PECA, which achieved release‐controlling of dye at different pH. This method provides solution for surface modification of fragile hydrogel capsules to effectively control the releasing of liquid core, which is highly valuable in the field of food, cosmetic, and medical delivery.

Yeast-laden hydrogel capsules for scalable trace lead removal from water

Hydrogel capsules are used to encapsulate yeast for the scalable and efficient removal of trace lead from water.

Engineering peptide-modified alginate-based bioinks with cell-adhesive properties for biofabrication.

Alginate (ALG) and its oxidised form alginate-dialdehyde (ADA) are highly attractive materials for hydrogels used in 3D bioprinting as well as drop-on-demand (DoD) approaches. However, both polymers need to be modified using cell-adhesive peptide sequences, to obtain bioinks exhibiting promising cell-material interactions. Our study explores the modification of ALG- and ADA-based bioinks with the adhesive peptides YIGSR (derived from laminin), RRETEWA (derived from fibronectin) and IKVAV (derived from laminin) for 3D bioprinting. Two coupling methods, carbodiimide and Schiff base reactions, were employed to modify the polymers with peptides. Analytical techniques, including FTIR and NMR were used to assess the chemical composition, revealing challenges in confirming the presence of peptides. The modified bioinks exhibited decreased stability, viscosity, and stiffness, particularly-ADA-based bioinks in contrast to ALG. Sterile hydrogel capsules or droplets were produced using a manual manufacturing process and DoD printing. NIH/3T3 cell spreading analysis showed enhanced cell spreading in carbodiimide-modified ADA, Schiff base-modified ADA, and PEG-Mal-modified ADA. The carbodiimide coupling of peptides worked for ADA, however the same was not observed for ALG. Finally, a novel mixture of all used peptides was evaluated regarding synergistic effects on cell spreading which was found to be effective, showing higher aspect ratios compared to the single peptide coupled hydrogels in all cases. The study suggests potential applications of these modified bioinks in 3D bioprinting approaches and highlights the importance of peptide selection as well as their combination for improved cell-material interactions.

Synthesis and pH-responsive properties of bacteria mimicking hydrogel capsules

Synthetic imitation of nonspherical microorganisms can enhance therapeutic delivery in the body. Hydrogel microcapsules with bacteria-mimicking shapes were synthesized through a multilayer assembly of polymers on sacrificial microparticle surfaces.

Controllable microfluidic fabrication of honeycomb capsule adsorbent via the one-step titration-gel method

The hydrogel capsule adsorbent with honeycomb architectures was prepared via the one-step titration-gel method (OSTGM), which the casting solution contained polyvinyl alcohol (PVA), sodium alginate (SA) and tetraethyl orthosilicate (TEOS) were directly dripped into CaCl2 and H3BO3 aqueous mixture through a controllable microfluidic device. The microscopic morphology and adsorbed capacity of the SA-PVA-SiO2 capsules (SPSC) were absolutely depended on the parameter conditions during preparation. In this paper, at optimal synthesis situations [SA: PVA = 3: 7 (w: w), TEOS: (SA-PVA) = 2: 30 (v: w), the titration-gel distance was 14 cm and the feed flowed rate was 13 mL/h], the maximal removed capacity of the MB by the SPSC was 392.54 mg/g, and the SiO2 NPs accounted for 17.94 wt % of the polymers. The prepared SPSC, also, could work in overly acid and alkaline aqueous solutions (pH 1-13). The authors of this manuscript hoped this work would provide a corresponding guideline for the researchers who are aiming at preparing the spherical hydrogel adsorbents for waste water treatments.

Encapsulation of Amyloglucosidase in Chitosan-SDS Coacervates as a Means to Control Starch Hydrolysis in Plant-Based Beverages

Starch enzymatic hydrolysis is a key technology for preparing plant-based dairy alternative beverages, preferred for its low energy consumption, high product yield, and quality. However, the high-temperature requirement to terminate reactions and challenges in continuous operations hinder enzyme applicability. Therefore, encapsulation techniques have been explored to address these limitations, enhancing the enzyme’s stability and facilitating process control. This study developed a novel amyloglucosidase encapsulation system based on chitosan-SDS hydrogel capsules produced by simple coacervation. The enzymatic activity of free and immobilised amyloglucosidase was assessed using corn starch and maltose as substrates. The encapsulation process successfully yielded self-supporting structured and spherical capsules, achieving an immobilisation yield of 71% and an enzyme efficiency of 83%. The residual enzymatic activity after 28 days of storage remained at 76%. A feedback inhibition investigation was performed by varying the concentration of corn starch, and favourable applicability of encapsulated amyloglucosidase for continuous processes was found. The encapsulation process offered several advantages, such as a straightforward separation step to halt enzymatic reactions and no need for high temperatures that may affect food product attributes. Lastly, the amyloglucosidase-chitosan-SDS coacervates show promise in improving enzyme stability, facilitating hydrolysis control, and expanding enzyme utilisation in dairy alternative plant beverage manufacture.

Developing Water Barrier Coatings of Millimeter-Scale Hydrogel Capsules via Interfacial Initiated Ethyl Cyanoacrylate by In-Situ Polymerization

The millimeter-scale capsules for oil encapsulation have been used successfully in food, cosmetic and pharmaceutical engineering. However, aqueous core capsules still have poor barrier properties and a short storage life. In this work, a rapid and mild coating method was applied on millimeter-scale calcium alginate aqueous core capsules (mm-CaSA-Caps). A layer of poly(ethyl-cyanoacrylate) (PECA) was coated on the surface of the mm-CaSA-Caps using interfacial polymerization. The PECA-coated mm-CaSA-Caps (PECA@CaSA-Caps) prepared in the trichloromethane maintained a spherical shape in wet and dry conditions. Compared with the mm-CaSA-Caps, the weight loss ratio of water in the PECA@CaSA-Caps decreased by 38.59%. The release rates of dye in PECA@CaSA-Caps greatly reduced in neutral (pH 7.0), alkaline (pH 10.0) and acidic (pH 1.0) conditions. This work provides a new way to improve the barrier properties and storage life of hydrogel capsules.

Cellulose-Based Hydrogel Capsules to Address Soil Erosion Following Wildfire

While natural forest fires promote regrowth and restoration within an ecosystem, a major cause for concern in Canada is deforestation due to an increased prevalence of wildfires brought about by industry practices and climate change. This has become even more evident recently with the wildfires burning in remote areas of British Columbia, Alberta, Ontario, and Quebec, creating smoke-related air pollution observed in many communities throughout Canada and the United States. Entwistle, Alberta, specifically, experienced severe wildfire during late April to early May of this year (2023), leading to numerous resident evacuations while firefighters worked to contain the blaze. Our proposed grassroots initiative involves the use of biodegradable cellulose-based hydrogels to promote water retention and soil health in the fire-ravaged forested areas of Entwistle, Alberta. Cellulose is the most abundant renewable biopolymer and is utilized for the synthesis of bio-based hydrogel. It is a green and sustainable material, giving it a biocompatible advantage over petroleum-based and synthetic hydrogels that possess toxic effects. It is derived from plant material and is fully biodegradable. Soil becomes dehydrated as a result of wildfire, with decreased water content and microbe presence leading to soil erosion and deeply impacting regeneration of forests. This has negative impacts on the broader environment, as well as on humans and non-human animals. The use of hydrogels to restore and maintain soil moisture levels, pH, and microbial environments is a novel approach to better maintain forest health from a One Health perspective.

Hydrogel capsules as new approach for increasing drying survival of plant biostimulant gram-negative consortium

Several plant growth–promoting bacteria (PGPB) are gram-negative, and their cell viability is affected during the bio-inoculant production. Hence, formulation-drying processes provide challenges that limit the adoption of these beneficial microorganisms in sustainable agricultural production. Among delivery system strategies for gram-negative PGPB, the encapsulating cells in biopolymeric materials are emerging as a promising alternative. This research aims to evaluate the effect of additives and crosslinking agents on the survival of the consortium of Herbaspirillum frisingense AP21, Azospirillum brasilense D7, and Rhizobium leguminosarum T88 in hydrogel capsules. Three crosslinkers and diverse potential drying protectors were tested. Calcium gluconate provides notable consortium survival advantages regarding colony-forming units (CFUs) (losses of up to 4 log CFU) compared to calcium lactate and calcium chloride (up to 6 log CFU). Additives such as skimmed milk, whey protein, and Gelita® EC improve the recovery of viable cells after the drying process, demonstrating an increase in cell survival of the three bacteria by up to 4 log CFU. The combination of these substances into a capsule prototype extends the storage stability of bacterial consortium up to 3 months at 18 ± 2 °C. This study expands the knowledge for formulating gram-negative PGPB consortium, regarding the crosslinker and drying protector relationship on encapsulation processes with drying survival and further storage stability performance.Key points• Hydrogel immobilization formulation approach for PGPB consortium• Enhancing drying survival of gram-negative PGPB consortium• Increasing storage stability of PGPB consortium at 18 °C

3D-to-4D Structures: an Exploration in Biomedical Applications.

3D printing is a cutting-edge technique for manufacturing pharmaceutical drugs (Spritam), polypills (guaifenesin), nanosuspension (folic acid), and hydrogels (ibuprofen) with limitations like the choice of materials, restricted size of manufacturing, and design errors at lower and higher dimensions. In contrast, 4D printing represents an advancement on 3D printing, incorporating active materials like shape memory polymers and liquid crystal elastomers enabling printed objects to change shape in response to stimuli. 4D printing offers numerous benefits, including greater printing capacity, higher manufacturing efficiency, improved quality, lower production costs, reduced carbon footprint, and the ability to produce a wider range of products with greater potential. Recent examples of 4D printing advancements in the clinical setting include the development of artificial intravesicular implants for bladder disorders, 4D-printed hearts for transplant, splints for tracheobronchomalacia, microneedles for tissue wound healing, hydrogel capsules for ulcers, and theragrippers for anticancer drug delivery. This review highlights the advantages of 4D printing over 3D printing, recent applications in manufacturing smart pharmaceutical drug delivery systems with localized action, lower incidence of drug administration, and better patient compliance. It is recommended to conduct substantial research to further investigate the development and applicability of 4D printing in the future.

Hydrogel capsule-based digital quantitative polymerase chain reaction.

Droplet digital PCR (ddPCR) is accurate in nucleic acid quantification owing to its linearity and high sensitivity. Amplification of nucleic acid in droplets, however, is limited by the stability of droplets against thermal cycling. While the use of fluorinated oil or supplementation of surfactant could improve the stability of droplets, this process has also greatly increased the cost of ddPCR and limited post-PCR analysis. Here, we report a novel method known as gel capsule-based digital PCR (gc-dPCR) which includes amethod to prepare hydrogel capsules encapsulating thePCR reaction mix, conducting PCR reaction, and readout by either quantitativePCR (qPCR)system or fluorescence microplate reader. We have compared the developedmethod to vortex ddPCR. Our approach results in higher fluorescence intensity compared to ddPCR suggesting higher sensitivity of the system. As hydrogel capsules are more stable than droplets in fluorinated oil throughout thermal cycling, all partitions can be quantified, thus preventing loss of information from low-concentration samples. The newapproach should extend to all droplet-based PCR methods. Ithas greatly improved ddPCR by increasing droplets stability and sensitivity, and reducing the cost of ddPCR, which help to remove the barrier of ddPCR in settings with limited resources.

Delivery of soluble ethinylestradiol complex by pH‐responsive core‐shell composite hydrogel capsules

AbstractEthinylestradiol (EE) is a potent estrogen widely used to treat diseases such as breast cancer, prostate cancer, and menopausal syndrome. The poor aqueous solubility of EE leads to erratic oral absorption, resulting in suboptimal plasma levels. Developing a formulation to enhance the solubility of EE in the gastrointestinal tract would be beneficial to increase the bioavailability of EE. Thereafter, we prepare diethylenetriamine‐β‐cyclodextrin/ethinylestradiol (DETA‐β‐CD/EE) complex, aiming to increase the solubility of EE in water, and design and prepare core‐shell composite hydrogel capsules with aldocellulose and hydroxyethyl cellulose as the core and sodium alginate as the shell. The stability, swelling, drug release behavior and biocompatibility of the core‐shell hydrogel capsules are carefully investigated. And the results show that the prepared hydrogel capsules have the controlled and sustained release ability of soluble DETA‐β‐CD/EE, can achieve pH‐responding to intestinal fluid, and are non‐toxic to normal human cells.

Engineered cell-based therapies in ex vivo ready-made CellDex capsules have therapeutic efficacy in solid tumors

Encapsulated cell-based therapies for solid tumors have shown promising results in pre-clinical settings. However, the inability to culture encapsulated therapeutic cells prior to their transplantation has limited their translation into clinical settings. In this study, we created a wide variety of engineered therapeutic cells (ThC) loaded in micropore-forming gelatin methacryloyl (GelMA) hydrogel (CellDex) capsules that can be cultured in vitro prior to their transplantation in surgically debulked solid tumors. We show that both allogeneic and autologous engineered cells, such as stem cells (SCs), macrophages, NK cells, and T cells, proliferate within CellDex capsules and migrate out of the gel in vitro and in vivo. Furthermore, tumor cell specific therapeutic proteins and oncolytic viruses released from CellDex capsules retain and prolong their anti-tumor effects. In vivo, ThCs in pre-manufactured Celldex capsules persist long-term and track tumor cells. Moreover, chimeric antigen receptor (CAR) T cell bearing CellDex (T-CellDex) and human SC releasing therapeutic proteins (hSC-CellDex) capsules show therapeutic efficacy in metastatic and primary brain tumor resection models that mimic standard of care of tumor resection in patients. Overall, this unique approach of pre-manufactured micropore-forming CellDex capsules offers an effective off-the-shelf clinically viable strategy to treat solid tumors locally.

Quantifying the water donation potential of commercial and corn starch hydrogels in a cementitious matrix

In this study, we introduce a new methodology to quantify the internal curing potential of hydrogels in a cementitious matrix. The swollen Super Absorbent Polymers (SAPs) and newly synthesized corn-starch hydrogels are investigated by embedding a capsule filled with swollen hydrogel in a cement mortar cube and monitoring the internal wetting area around the hydrogel capsule for 56 days. Our findings demonstrate that all of the investigated hydrogels serve as effective internal curing agents, releasing water in a cyclic pattern governed by the humidity gradient between the hydrogel and the surrounding matrix. Moreover, the regions around the hydrogel capsules display a denser accumulation of calcium silicate hydrate (CSH) gel, indicating improved hydration due to internal curing from the hydrogels. This research offers valuable understanding into the possibilities of utilizing bio-based materials and SAPs for internal curing and the creation of environmentally friendly cementitious materials. In summary, the proposed innovative approach serves as an effective way for measuring the internal curing capabilities of hydrogels within cementitious materials.

Silica-Calcium-Alginate Hydrogels for the Co-Immobilization of Glucose Oxidase and Catalase to Reduce the Glucose in Grape Must.

Higher temperatures due to climate change are causing greater sugar production in grapes and more alcoholic wines. The use of glucose oxidase (GOX) and catalase (CAT) in grape must is a biotechnological green strategy to produce reduced-alcohol wines. GOX and CAT were effectively co-immobilized by sol-gel entrapment in silica-calcium-alginate hydrogel capsules. The optimal co-immobilization conditions were achieved at a concentration of the colloidal silica, sodium silicate and sodium alginate of 7.38%, 0.49% and 1.51%, respectively, at pH 6.57. The formation of a porous silica-calcium-alginate structure was confirmed by environmental scanning electron microscopy and the elemental analysis of the hydrogel by X-ray spectroscopy. The immobilized GOX showed a Michaelis-Menten kinetic, while the immobilized CAT fits better to an allosteric model. Immobilization also conferred superior GOX activity at low pH and temperature. The capsules showed a good operational stability, as they could be reused for at least 8 cycles. A substantial reduction of 26.3 g/L of glucose was achieved with encapsulated enzymes, which corresponds to a decrease in potential alcoholic strength of must of about 1.5% vol. These results show that co-immobilized GOX and CAT in silica-calcium-alginate hydrogels is a promising strategy to produce reduced-alcohol wines.

Stimuli-sensitive and degradable capsules as drug carriers with decreased toxicity against healthy cells

Novel hollow hydrogel capsules, stimuli-sensitive and degradable polymer-based, were synthesized. These capsules were prepared by a facile method based on precipitation polymerization of N-isopropylacrylamide (NIPA) with crosslinking agent -N,N′-bis(acryloyl)cystine (BISS) on -C = C- modified sacrificial dimethyldiethoxysilane emulsion templates (DMDES). The capsules were formed after the removal of the silica core by ethanol. The presence of carboxylic groups from BISS gave the capsules stability and sensitivity to pH. The presence of the -S-S- groups, in turn, made the polymer network susceptible to degradation by the reducing agent glutathione, which is present at elevated concentration in some cancer cells. The anticancer drug Doxorubicin (DOX) was loaded and released from capsules after their degradation. The highest release of drug was observed at 37 °C and cGSH = 40 mM, which corresponds well with the conditions present in most cancer cells. The MTT assay indicated that the DOX-loaded capsules were more cytotoxic against MCF-7 breast cancer cells than DOX alone. Importantly, they were less toxic against the healthy MCF-10A cells. The unloaded gel nanoparticles did not inhibit proliferation of the cells.

Innovative hydrogels use in the germination and growth of tree species Paulownia tomentosa and Cupressus sempervirens

Research goal: This article presents the results of a research project aimed at demonstrating the effects and benefits of using an organic ingredient, hydrogel (Hydro Start), to improve the germination and growth of Paulownia tomentosa and Cupressus sempervirens seedlings. Materials and Methods: The experiments started in May 2022 and were conducted in the CREA-OF greenhouses in Pescia (PT) on seeded plants of Paulownia tomentosa and Cupressus sempervirens. The seeds were placed in pots with various hydrogel capsules to determine whether there were any effects on germination and plant growth. Agronomic analyses of the seeds and plants, microbiological analyses and substrate evaluation were also conducted. Results and Discussion: The experiment showed that the use of hydrogel can improve the quality and resistance of sown plants of Paulownia tomentosa and Cupressus sempervirens. In general, the improvement in average germination time and plant growth was proportional to the number of hydrogel capsules inserted into the substrate at the time of sowing; this also influenced the microbial colonisation of the soil. Studies show that the water retained by the hydrogel forms a water reserve in the soil that can increase the water uptake efficiency of plants. Mixing superabsorbent materials (hydrogels) with soils or growing media can significantly increase the water-holding capacity of the soil. Water is available to plants for a longer period of time, making them more resistant, especially during transplanting. Furthermore, the incorporation of hydrogels into the soil or growing media allows for improved germination, plant growth and nutrient and water uptake. Conclusions: Research shows that hydrogels can be used in a variety of ways due to their ability to retain water. These innovations can also ensure and promote plant survival in drought conditions. The results show that new hydrogels need to be evaluated not only for their physical properties, but also for their biological attributes related to the positive and negative aspects that bind microorganisms to plants.