Hydrogel Microcapsules Research Articles

Primary Human Pancreatic Cancer Cells Cultivation in Microfluidic Hydrogel Microcapsules for Drug Evaluation.

Chemotherapy is an essential postoperative treatment for pancreatic cancer, while due to the lack of effective drug evaluation platforms, the therapeutic outcomes are hampered by tumor heterogeneity among individuals. Here, a novel microfluidic encapsulated and integrated primary pancreatic cancer cells platform is proposed for biomimetic tumor 3D cultivation and clinical drug evaluation. These primary cells are encapsulated into hydrogel microcapsules of carboxymethyl cellulose cores and alginate shells based on a microfluidicelectrospraytechnique. Benefiting from the good monodispersity, stability, and precise dimensional controllability of the technology, the encapsulated cells can proliferate rapidly and spontaneously form 3D tumor spheroids with highly uniform size and good cell viability. By integrating these encapsulated tumor spheroids into a microfluidic chip with concentration gradient channels and culture chambers, dynamic and high-throughput drug evaluation of different chemotherapy regimens could be realized. It is demonstrated that different patient-derived tumor spheroids show different drug sensitivity on-chip, which is significantly consistent with the clinical follow-up study after the operation. The results demonstrate that the microfluidic encapsulated and integrated tumor spheroids platform has great application potential in clinical drug evaluation.

The Influence of the Use of Different Polysaccharide Coatings on the Stability of Phenolic Compounds and Antioxidant Capacity of Chokeberry Hydrogel Microcapsules Obtained by Indirect Extrusion.

The aim of the study was to evaluate the effect of the use of different polysaccharides and their mixtures on the structure of chokeberry hydrogel microcapsules and the stability of polyphenolic compounds and antioxidant capacity during one month of refrigerated storage. As a coating material, alginate and its mixtures with pectin, carrageenan, and chitosan were used, while chokeberry juice and preparation of polyphenolic compounds were used as a core. In non-stored capsules, the addition of carrageenan, pectin, and chitosan to alginate increased the content of total polyphenolic compounds and antioxidant capacity. When compared to non-encapsulated juice, the capsules had a greater decrease in antioxidant capacity during storage. The coating variant composed of alginate and carrageenan was found to be the most beneficial for the preservation of the capsules' phenolic compounds. The findings revealed that proper polysaccharide coating selection is critical for the proper course of the microencapsulation process, the polyphenolic content of chokeberry capsules, and their antioxidant properties.

DNA-Tetrahedra Corona-Modified Hydrogel Microcapsules: "Smart" ATP- or microRNA-Responsive Drug Carriers.

The assembly of adenosine triphosphate (ATP)-responsive and miRNA-responsive DNA tetrahedra-functionalized carboxymethyl cellulose hydrogel microcapsules is presented. The microcapsules are loaded with the doxorubicin-dextran drug or with CdSe/ZnS quantum dots as a drug model. Selective unlocking of the respective microcapsules and the release of the loads in the presence of ATP or miRNA-141 are demonstrated. Functionalization of the hydrogel microcapsules a with corona of DNA tetrahedra nanostructures yields microcarriers that revealed superior permeation into cells. This is demonstrated by the effective permeation of the DNA tetrahedra-functionalized microcapsules into MDA-MB-231 breast cancer cells, as compared to epithelial MCF-10A nonmalignant breast cells. The superior permeation of the tetrahedra-functionalized microcapsules into MDA-MB-231 breast cancer cells, as compared to analog control hydrogel microcapsules modified with a corona of nucleic acid duplexes. The effective permeation of the stimuli-responsive, drug-loaded, DNA tetrahedra-modified microcapsules yields drug carriers of superior and selective cytotoxicity toward cancer cells.

Oral delivery of stem-cell-loaded hydrogel microcapsules restores gut inflammation and microbiota.

Mesenchymal stem cells (MSCs) are an attractive candidate for the treatment of inflammatory bowel disease (IBD), but their poor delivery rate to an inflamed colon is a major factor hampering the clinical potential of stem cell therapies. Moreover, there remains a formidable hurdle to overcome with regard to survival and homing in to injured sites. Here, we develop a strategy utilizing monodisperse hydrogel microcapsules with a thin intermediate oil layer prepared by a triple-emulsion drop-based microfluidic approach as an in-situ oral delivering carrier. The oral delivery of stem-cell-loaded hydrogel microcapsules (SC-HM) enhances MSC survival and retention in the hostile stomach environment due to the intermediate oil layer and low value of the overall stiffness, facilitating programmable cell release during gastrointestinal peristalsis. SC-HM is shown to induce tissue repair, reduce the colonic macrophage infiltration responsible for the secretion of the pro-inflammatory factors, and significantly mitigate the severity of IBD in a mouse model, where MSCs released by SC-HM successfully accumulate at the colonic crypt. Moreover, a metagenomics analysis reveals that SC-HM ameliorates the dysbiosis of specific bacterial genera, including Bacteroides acidifaciens, Lactobacillus (L.) gasseri, Lactobacillus reuteri, and L. intestinalis, implying optimization of the microorganism's composition and abundance. These findings demonstrate that SC-HM is a potential IBD treatment candidate.

Hyaluronic acid/gelatin microcapsule functionalized with carbon nanotube through laccase-catalyzed crosslinking for fabrication of cardiac microtissue.

Carbon nanotube (CNT) and gelatin (Gela) molecules are effective substrates in promoting engineered cardiac tissue functions. This study developed a microfluidic-based encapsulation process for biomimetic hydrogel microcapsule fabrication. The hydrogel microcapsule was produced through a coaxial double orifice microfluidic technique and a water-in-oil emulsion system in two sequential processes. The phenol (Ph) substituted Gela (Gela-Ph) and CNT (CNT-Ph), respectively as cell-adhesive and electrically conductive substrates were incorporated in hyaluronic acid (HA)-based hydrogel through laccase-mediated crosslinking. The Cardiomyocyte-enclosing microcapsule fabricated and cellular survival, function, and possible difference in the biological activity of encapsulated cells within micro vehicles were investigated. The coaxial microfluidic method and Lac-mediated crosslinking reaction resulted in spherical vehicle production in 183 μm diameter at 500 capsules/min speed. The encapsulation process did not affect cellular viability and harvested cells from microcapsule proliferated well likewise subcultured cells in tissue culture plate. The biophysical properties of the designed hydrogel, including mechanical strength, swelling, biodegradability and electroconductivity upregulated significantly for hydrogels decorated covalently with Gela-Ph and CNT-Ph. The tendency of the microcapsule for the spheroid formation of cardiomyocytes inside the proposed microcapsule occurred 3 days after encapsulation. Interestingly, immobilized Gela-Ph and CNT-Ph promote cellular growth and specific cardiac markers. Overall, the microfluidic-based encapsulation technology and synthesized biomimetic substrates with electroconductive properties demonstrate desirable cellular adhesion, proliferation, and cardiac functions for engineering cardiac tissue.

Hydrogel microcapsules containing engineered bacteria for sustained production and release of protein drugs

Subcutaneous administration of sustained-release formulations is a common strategy for protein drugs, which avoids first pass effect and has high bioavailability. However, conventional sustained-release strategies can only load a limited amount of drug, leading to insufficient durability. Herein, we developed microcapsules based on engineered bacteria for sustained release of protein drugs. Engineered bacteria were carried in microcapsules for subcutaneous administration, with a production-lysis circuit for sustained protein production and release. Administrated in diabetic rats, engineered bacteria microcapsules was observed to smoothly release Exendin-4 for 2 weeks and reduce blood glucose. In another example, by releasing subunit vaccines with bacterial microcomponents as vehicles, engineered bacterial microcapsules activated specific immunity in mice and achieved tumor prevention. The engineered bacteria microcapsules have potential to durably release protein drugs and show versatility on the size of drugs. It might be a promising design strategy for long-acting in situ drug factory.

Effect of hydrogel microcapsule on shrinkage and mechanical properties of cement mortars

Superabsorbent polymer (SAP) shows a good internal curing effect in cement-based materials, but its volume changes greatly after it releases water. This occurrence causes adverse effects on the properties of cement-based materials. Microcapsules were prepared with calcium alginate hydrogel as the shell and epoxy resin as the core material to mitigate these adverse effects. The effects of microcapsules on the shrinkage and mechanical properties of cement mortars were analysed by observing such parameters as the heat of hydration and relative humidity of the mortars, and such techniques as mercury intrusion porosimetry. The results showed that microcapsules can delay the hydration of cement and provide a superior early shrinkage reduction effect when compared with SAP. In addition, the presoaked microcapsules left pores that were smaller in diameter than those observed in the SAP mortars. As a result, the influence of microcapsules on the mortar's compressive strength was found to be less than that of SAP. Therefore, the compressive strength of the mortars containing microcapsules was essentially the same as that of the mortars containing SAP when the presoaked microcapsule content was 35 times that of the presoaked SAP content.

Poly‐γ‐Glutamic Acid Microgel‐Encapsulated Probiotics with Gastric Acid Resistance and Smart Inflammatory Factor Targeted Delivery Performance to Ameliorate Colitis

AbstractHydrogel microspheres with probiotic‐loaded therapy have been considered an effective and safe strategy for treating inflammatory bowel disease (IBD). However, the low survival rate under harsh stomach conditions and inflam‐matory cytokine target release efficiency remains a major challenge for their application. Herein, a novel NO‐responsive poly‐γ‐glutamic acid (γ‐PGA) hydrogel microcapsule (NRPM) strategy based on a droplet microfluidic technology platform is proposed. Accordingly, highly uniform microspheres with high cell densities (6.0 × 108 cells mL−1) and a wide range of diameters (100–600 μm) are produced, which are critical for realizing accurate down‐stream evaluation and applications. Owing to the cytoprotective effects of the NRPM, the decorated probiotics showed high viability in the simulated gastric (89.67%) and intestinal (93.67%) fluid environments, while the data are 0% and 61.60% for free cells, respectively. Moreover, both in vitro and in vivo studies demonstrate that microspheres can respond to nitric oxide (NO) stimuli and rapidly release probiotics to maintain the intestinal mechanical barrier and regulate the balance of intestinal flora. Consequently, NRPM significantly increases the treatment efficacy against dextran sulfate sodium‐induced colitis in a mouse model. The results demonstrate that NRPM is a promising approach for improving the efficacy of orally administered probiotics in patients with colonic IBD.

Cell-Inspired Hydrogel Microcapsules with a Thin Oil Layer for Enhanced Retention of Highly Reactive Antioxidants.

In nature, individual cells are compartmentalized by a membrane that protects the cellular elements from the surrounding environment while simultaneously equipped with an antioxidant defense system to alleviate the oxidative stress resulting from light, oxygen, moisture, and temperature. However, this mechanism has not been realized in cellular mimics to effectively encapsulate and retain highly reactive antioxidants. Here, we report cell-inspired hydrogel microcapsules with an interstitial oil layer prepared by utilizing triple emulsion drops as templates to achieve enhanced retention of antioxidants. We employ ionic gelation for the hydrogel shell to prevent exposure of the encapsulated antioxidants to free radicals typically generated during photopolymerization. The interstitial oil layer in the microcapsule serves as an stimulus-responsive diffusion barrier, enabling efficient encapsulation and retention of antioxidants by providing an adequate pH microenvironment until osmotic pressure is applied to release the cargo on-demand. Moreover, addition of a lipophilic reducing agent in the oil layer induces a complementary reaction with the antioxidant, similar to the nonenzymatic antioxidant defense system in cells, leading to enhanced retention of the antioxidant activity. Furthermore, we show the complete recovery and even further enhancement in antioxidant activity by lowering the storage temperature, which decreases the oxidation rate while retaining the complementary reaction with the lipophilic reducing agent.

Visual pressure interactive display of alternating current electroluminescent devices based on hydrogel microcapsules

In this study, microcapsules are combined with electroluminescent devices. When the microcapsules are subjected to a certain external force, the core material is crushed and overflows, so that the devices emit light at the corresponding position.

Topologically switchable and gated transcription machinery.

Topological barriers control in nature the transcription machinery, thereby perturbing gene expression. Here we introduce synthetically designed DNA templates that include built-in topological barriers for switchable, triggered-controlled transcription of RNA aptamers. This is exemplified with the design of transcription templates that include reversible and switchable topological barriers consisting of a Sr2+-ion-stabilized G-quadruplex and its separation by kryptofix [2.2.2], KP, for the switchable transcription of the malachite green (MG) RNA aptamer, the T-A·T triplex barrier being separated by a fuel-strand for the cyclic triggered transcription of the 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI)-binding aptamer, and the use of a photoactivated cis/trans azobenzene-modified nucleic acid barrier for the switchable “ON”/“OFF” transcription of the MG RNA aptamer. By applying a mixture of topologically triggered templates consisting of the photoresponsive barrier and the T-A·T triplex barrier, the gated transcription of the MG aptamer or the DFHBI-binding aptamer is demonstrated. In addition, a Sr2+-ion/KP topologically triggered DNA tetrahedra promoter-transcription scaffold, for the replication of the MG RNA aptamer, and T7 RNA polymerase are integrated into DNA-based carboxymethyl cellulose hydrogel microcapsules acting as cell-like assemblies. The switchable, reversible transcription of the MG RNA aptamer in a cell-like containment is introduced.

Micro-ecology restoration of colonic inflammation by in-Situ oral delivery of antibody-laden hydrogel microcapsules.

In-situ oral delivery of therapeutic antibodies, like monoclonal antibody, for chronic inflammation treatment is the most convenient approach compared with other administration routes. Moreover, the abundant links between the gut microbiota and colonic inflammation indicate that the synergistic or antagonistic effect of gut microbiota to colonic inflammation. However, the antibody activity would be significantly affected while transferring through the gastrointestinal tract due to hostile conditions. Moreover, these antibodies have short serum half-lives, thus, require to be frequently administered with high doses to be effective, leading to low patient tolerance. Here, we develop a strategy utilizing thin shell hydrogel microcapsule fabricated by microfluidic technique as the oral delivering carrier. By encapsulating antibodies in these microcapsules, antibodies survive in the hostile gastrointestinal environment and rapidly release into the small intestine through oral administration route, achieving the same therapeutic effect as the intravenous injection evaluated by a colonic inflammation disease model. Moreover, the abundance of some intestinal microorganisms as the indication of the improvement of inflammation has remarkably altered after in-situ antibody-laden microcapsules delivery, implying the restoration of micro-ecology of the intestine. These findings prove our microcapsules are exploited as an efficient oral delivery agent for antibodies with programmable function in clinical application.

Bioactive hydrogel microcapsules for guiding stem cell fate decisions by release and reloading of growth factors

Human pluripotent stem cells (hPSC) hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure. Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols. In this paper, we sought to address these challenges through the development of bioactive microcapsules. A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell. Importantly, the shell contained heparin moieties for growth factor (GF) binding and release. The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation. Specifically, we demonstrated that one-time, 1 h long loading of pluripotency signals, fibroblast growth factor (FGF)-2 and transforming growth factor (TGF)-β1, into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs. Furthermore, stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue, Nodal, resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol. Overall, bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.

Targeted Delivery of Narrow-Spectrum Protein Antibiotics to the Lower Gastrointestinal Tract in a Murine Model of Escherichia coli Colonization.

Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.

Enabling direct dense encapsulation of water-insoluble powder in hydrogel microcapsules by bubble-assisted encapsulation method

Encapsulating powder ingredients into hydrogel with programmable release ability is highly demanded in many fields including food engineering, medical and healthcare fields. However, directly adding water-insoluble powders into pre-gel solution makes the mixture susceptible to clogging problems during processing, thus limiting the loading rate. To address this problem, a new way to encapsulate water-insoluble powder ingredients without addition of any organic solvent named bubble-assisted encapsulation method is developed in this study. The powders were firstly encapsulated in hydrogel bubbles and further dispersed by T-shaped microfluidic flow to form the core/shell-structured powder in hydrogel microcapsules (P/H microcapsules). The obtained P/H microcapsules had an exceptionally high loading rate of water-insoluble powders up to 94.76%. The P/H microcapsules were freeze-dried for long-term storage, and meanwhile, the as-prepared microcapsules were able to swell rapidly to soft state before use. Moreover, with the well-defined core–shell structure, the P/H microcapsules were endowed with dual release capabilities to external stimuli. The bubble-assisted encapsulation method that enables direct dense encapsulation of powder ingredients at a high loading rate appears promising for water-insoluble food or pharmaceutical ingredients delivery.

(Invited) On-Chip Characterization of Microcapsules Using a Capacitive Sensor for Microencapsulation and Single-Cell Analysis Applications

Introduction Droplet microfluidics has emerged as a versatile tool for a wide range of biomedical applications. Recently, various types of microfluidic droplet-generation platforms such as T-junction, flow-focusing, and co-flow, have been used for high throughput generation of microcapsules containing cells, drugs and biomolecules. microfluidic microencapsulation is a fast and well-controlled method for the generation of uniform microcapsules with the capability of tuning the size and physicochemical properties of microcapsules during the encapsulation process [1,2].In a microfluidic droplet generation system, droplet formation can be widely classified into three regimes (squeezing, dripping, and jetting). The quality of the generated droplets in terms of stability and uniformity can be highly affected by the type of flow regimes. Since the flow regime and size of the droplets can be influenced by a small change in the system variables (such as the flow rate ratio of the dispersed and continuous phase), real-time monitoring of the droplet generation is vital especially for biomedical applications [3,4].To address the above challenges, in this work we developed microfluidic droplet generation devices (T-junction and flow-focusing) for a well-controlled encapsulation of probiotic bacteria. In order to characterize microcapsules, a capacitive sensor was designed and integrated into the chip. Finally, the performance of the fabricated microfluidic device for on-chip monitoring of the encapsulating process was evaluated. Materials and Methods The device is made out of gold microelectrodes integrated into a polydimethylsiloxane (PDMS) chip. The microfluidic chip was fabricated in a cleanroom facility using a glass substrate with electrodes patterned by photolithography and wet etching process. A microfluidic channel was then fabricated with inlets and outlets by pouring PDMS over a mold followed by bonding the PDMS channel to the glass slide via plasma treatment machine. The dispersion phase (DP) containing alginate and Escherichia coli DH5-alpha (E. coli DH5a), as a bacterial model, was injected through a central channel. The continuous phase (CP) was the mixture solution of mineral oil and span 80 that injected through the other channel. To characterize the generated microcapsules, the change in capacitance between the electrodes was recorded using a potentiostat as probiotic bacteria were encapsulated on the chip. Results and Conclusions E.coli cells were encapsulated inside of hydrogel microcapsules using the microfluidic device. The polymeric microcapsules, once ingested, will protect the probiotics in the acidic pH of the stomach and dissolve or swell in the intestine where the pH increases above 7 to release the entrapped probiotics. The proposed microfluidic microencapsulation method can be used for the high-throughput production of microencapsulates containing probiotic cells as new drug delivery systems.The size and shape of the generated microcapsules was precisely tuned by changing the flow rate ratio of the dispersed and continuous phases followed by measuring the capacitance between the microelectrodes. The results show that the size and shape of microcapsules, as well as the flow regime, can be determined by the sensors signal (Fig 1).Individual microcapsules can be identified based on differences in dielectric properties using impedance spectroscopy techniques which are non-invasive and label-free. The microcapsule characterization system permits will be a powerful tool for evaluating the microencapsulation process as well as calculating the number of produced microcapsules. Besides, there is a potential to calculate the number of single cells in each capsule if the method is optimized.Monodisperse droplet generation in microfluidic devices has wide biomedical applications such as drug encapsulation. Due to the fine control of individual droplets using the developed device, we hope this study attracts significant interest in food and pharmaceutical studies. Reference Zhu, Pingan, and Liqiu Wang. "Passive and active droplet generation with microfluidics: a review." Lab on a Chip1 (2017): 34-75.Chong, Zhuang Zhi, et al. "Active droplet generation in microfluidics." Lab on a Chip1 (2016): 35-58.Shang, Luoran, Yao Cheng, and Yuanjin Zhao. "Emerging droplet microfluidics." Chemical reviews12 (2017): 7964-8040Shi, Zhi, et al. "Step emulsification in microfluidic droplet generation: mechanisms and structures." Chemical Communications64 (2020): 9056-9066. Figure 1

Oxidation and RGD Modification Affect the Early Neural Differentiation of Murine Embryonic Stem Cells Cultured in Core-Shell Alginate Hydrogel Microcapsules

Directed neural differentiation of embryonic stem cells (ESCs) has been studied extensively to improve the treatment of neurodegenerative disorders. This can be done through stromal-cell derived inducing activity (SDIA), by culturing ESCs directly on top of a layer of feeder stromal cells. However, the stem cells usually become mixed with the feeder cells during the differentiation process, making it difficult to obtain a pure population of the differentiated cells for further use. To address this issue, a non-planar microfluidic device is used here to encapsulate murine ESCs (mESCs) in the 3D liquid core of microcapsules with an alginate hydrogel shell of different sizes for early neural differentiation through SDIA, by culturing mESC-laden microcapsules over a feeder layer of PA6 cells. Furthermore, the alginate hydrogel shell of the microcapsules is modified via oxidation or RGD peptide conjugation to examine the mechanical and chemical effects on neural differentiation of the encapsulated mESC aggregates. A higher expression of Nestin is observed in the aggregates encapsulated in small (∼300 μm) microcapsules and cultured over the PA6 cell feeder layer. Furthermore, the modification of the alginate with RGD facilitates early neurite extension within the microcapsules. This study demonstrates that the presence of the RGD peptide, the SDIA effect of the PA6 cells, and the absence of leukemia inhibition factor from the medium can lead to the early differentiation of mESCs with extensive neurites within the 3D microenvironment of the small microcapsules. This is the first study to investigate the effects of cell adhesion and degradation of the encapsulation materials for directed neural differentiation of mESCs. The simple modifications (i.e., oxidation and RGD incorporation) of the miniaturized 3D environment for improved early neural differentiation of mESCs may potentially enhance further downstream differentiation of the mESCs into more specialized neurons for therapeutic use and drug screening.

Engineering microcapsules to construct vascularized human brain organoids

Brain organoid is a promising technique with potential applications in developmental study, drug discovery and regenerative medicine, however, its practical values are restricted by poor flexibility, and lack of near-physiological structures or functions. Here, we present a multidisciplinary strategy to engineer novel vascularized human induced pluripotent stem cells (hiPSCs)-derived brain organoids system with biomimetic features using microfluidic hydrogel microcapsules. Due to the precise fluids control of microfluidic electrospray technology, its generated microcapsules enable the efficient encapsulation of hiPSCs-derived neural cells and formation of uniform human brain organoids. Through embedding microcapsules in hydrogel, vascularized brain organoids with structured organization and reasonable tissue size are established. We have found hiPSC-derived brain organoids with in vivo-like neural identity, brain region and layered cortex, as well as complex vascular networks, proving the capability to generate more relevant model of vascularized human brain. Thus, this biomimetic neural system could be injected for traumatic brain injury, and in vivo animal study has shown graft-to-host functional neural connectivity and neural regeneration, suggesting the organ-level functions for tissue repair. Our studies indicated that this simple, scalable and flexible system could be applied to develop biomimetic human tissues, which potentially advanced the organoid models for biomedical applications.

Hydrogel Microcapsules: Hydrogel Microcapsules with a Thin Oil Layer: Smart Triggered Release via Diverse Stimuli (Adv. Funct. Mater. 18/2021)

In article number 2009553, Hyomin Lee, Chang-Hyung Choi, and co-workers present hydrogel microcapsules with an intermediate thin oil layer that enable the smart release of a broad range of hydrophilic cargoes triggered via diverse stimuli. The osmotic pressure and the overall stiffness of the hydrogel microcapsules can be fine-tuned to control the onset time of release and the release behavior of multi-cargo encapsulated hydrogel microcapsules to be either simultaneous or selective.

Near-Infrared Light-, Magneto-, and pH-Responsive GO-Fe3O4/Poly(N-isopropylacrylamide)/alginate Nanocomposite Hydrogel Microcapsules for Controlled Drug Release.

Responsive hydrogels have found widespread applications in biomedical science and engineering fields, especially for drug delivery. Despite the superior performance of responsive hydrogels, challenges still exist in drug-delivery efficiency when environmental stimuli are weak. Recently, the demand in the design of hydrogel-based drug delivery systems has stimulated considerable interest in the search for new strategies, for instance, the application of nanocomposite hydrogels for reinforcing the versatility and flexibility in controlled drug delivery. In this study, a novel and effective nanocomposite hydrogel microcapsule drug delivery system, which is composed of poly(N-isopropylacrylamide) (PNIPAM) and alginate interpenetrating polymer and GO-Fe3O4 nanomaterials, is developed to achieve NIR light-, magneto-, and pH-responsive drug release. The GO-Fe3O4 nanomaterials embedded in the interpenetrating polymer enable the PNIPAM hydrogel deswelling by raising temperature above the lower critical solution temperature under NIR light and alternating magnetic field, thus accelerating the release of doxorubicin. In addition, the introduction of alginate into PNIPAM hydrogels endows nanocomposite hydrogels (NCHs) with quick gelation property, enhanced mechanical property, and pH-responsive performance. The in vitro cytotoxicity assay confirmed that the NCH platform can effectively kill the cancer cells. This novel multiresponsive drug delivery system holds great promise for the treatment of diseases.