Porous Microgels Research Articles

Gastrointestinal Self-Adaptive and Nutrient Self-Sufficient Akkermansia muciniphila-Gelatin Porous Microgels for Synergistic Therapy of Ulcerative Colitis.

To realize effective and long-term synergistic therapy of ulcerative colitis (UC) with probiotics, we developed gastrointestinal self-adaptive and nutrient self-sufficient Akkermansia muciniphila (AKK)-gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs, AKK was covered with sequential layers of proanthocyanidins (PAs), mucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC (AKK@PMP), and then encapsulated within the methacrylate-modified gelatin porous microgels. AKK@GPMGs provide sufficient mucus as a nutrition source for AKK and boost resistance to stomach acid by 30.49-fold, and colonization in the intestines is enhanced by 83.46 times. The microgels can be dissociated by matrix metalloproteinase at the inflammatory sites of the intestine, and release AKK@PMP, which acts as "band-aid" that adheres to the inflamed colon for a long time and offers improved synergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase reactive oxygen species scavenging capacity by 26.47 times, improve the intestinal mucus layer thickness by 5.63 times, increase the goblet cells abundance by 3.93 times, reduce intestinal permeability by 5.60 times and significantly enhance beneficial gut microbiota while repressing harmful microbiota. These results indicate that AKK@GPMGs can restore mucus layer and tight junction integrity, reduce inflammation and oxidative stress, and regulate gut microbiota homeostasis to effectively treat intestinal inflammation.

Ultra-stable Pickering liquid crystal-in-water emulsions decorated with thermoresponsive soft microgels and their response to aqueous analytes

This work presents an extensive investigation of the Pickering stabilization of liquid crystal (LC)-in-water emulsions using soft nanometer-sized colloidal poly(N-isopropylacrylamide) (PNIPAM) microgel particles and the responsivity of the PNIPAM microgel-stabilized Pickering LC droplet-based assembly towards amphiphilic analytes. The evolution of size and stability of LC droplets with microgel concentration are found to be dependent on the emulsifier-regime. Despite microgel coating, the LC-water interface remains accessible to model analytes such as anionic sodium dodecyl sulfate (SDS) and cationic dodecyltrimethylammonium bromide (DTAB). The analytes can pass through the interfacial pores and/or meshes of porous microgels to induce a bipolar-to-radial ordering transition within the droplets. The dose-response behaviour is largely influenced by the initial microgel concentration, type of analytes and interfacial layer (charge), and the number of droplets exposed to the analytes. The PNIPAM microgel-coated LC droplets notably exhibited enhanced sensitivity under conditions promoting electrostatic attractive interactions between the interfacial microgel layer and analytes. Overall, the results highlight the potential of Pickering LC-in-water emulsions for reliable and quantitative analysis of aqueous analytes, thus opening up new avenues toward the development of droplet-based optical sensors.

Microfluidics-assisted fabrication of natural killer cell-laden microgel enhances the therapeutic efficacy for tumor immunotherapy

Recently, interest in cancer immunotherapy has increased over traditional anti-cancer therapies such as chemotherapy or targeted therapy. Natural killer (NK) cells are part of the immune cell family and essential to tumor immunotherapy as they detect and kill cancer cells. However, the disadvantage of NK cells is that cell culture is difficult. In this study, porous microgels have been fabricated using microfluidic channels to effectively culture NK cells. Microgel fabrication using microfluidics can be mass-produced in a short time and can be made in a uniform size. Microgels consist of photo cross-linkable polymers such as methacrylic gelatin (GelMa) and can be regulated via controlled GelMa concentrations. NK92 cell-laden three-dimensional (3D) microgels increase mRNA expression levels, NK92 cell proliferation, cytokine release, and anti-tumor efficacy, compared with two-dimensional (2D) cultures. In addition, the study confirms that 3D-cultured NK92 cells enhance anti-tumor effects compared with enhancement by 2D-cultured NK92 cells in the K562 leukemia mouse model. Microgels containing healthy NK cells are designed to completely degrade after 5 days allowing NK cells to be released to achieve cell-to-cell interaction with cancer cells. Overall, this microgel system provides a new cell culture platform for the effective culturing of NK cells and a new strategy for developing immune cell therapy.

SDF-1 Bound Heparin Nanoparticles Recruit Progenitor Cells for Their Differentiation and Promotion of Angiogenesis after Stroke.

Angiogenesis after stroke is correlated with enhanced tissue repair and functional outcomes. The existing body of research in biomaterials for stroke focuses on hydrogels for the delivery of stem cells, growth factors, or small molecules or drugs. Despite the ability of hydrogels to enhance all these delivery methods, no material has significantly regrown vasculature within the translatable timeline of days to weeks after stroke. Here, two novel biomaterial formulations of granular hydrogels are developed for tissue regeneration after stroke: highly porous microgels (i.e., Cryo microgels) and microgels bound with heparin-norbornene nanoparticles with covalently bound SDF-1α. The combination of these materials results in perfused vessels throughout the stroke core in only 10 days, in addition to increased neural progenitor cell recruitment, maintenance, and increased neuronal differentiation.

Porous Microgels for Delivery of Curcumin: Microfluidics-Based Fabrication and Cytotoxicity Evaluation.

Polymeric microgels, fabricated via microfluidic techniques, have garnered significant interest as versatile drug delivery carriers. Despite the advances, the loading and release of hydrophobic drugs such as curcumin from polymeric microgels is not trivial. Herein, we report that effective drug loading can be achieved by the design of porous particles and the use of supramolecular cyclodextrin-based curcumin complexes. The fabrication of porous microgels through the judicious choice of chemical precursors under flow conditions was established. The evaluation of the curcumin loading dependence on the porosity of the microgels was performed. Microgels with higher porosity exhibited better curcumin loading compared to those with lower porosity. Curcumin-loaded microgels released the drug, which, upon internalization by U87 MG human glioma cancer cells, induced cytotoxicity. The findings reported here provide valuable insights for the development of tailored drug delivery systems using a microfluidics-based platform and outline a strategy for the effective delivery of hydrophobic therapeutic agents such as curcumin through supramolecular complexation.

A novel oleogel based on porous microgel from egg white

In this study, oleogel was prepared by oil absorption using egg white microgel (EWM), and the EWM was obtained through microwave hydrothermal treatment, freeze-thawing, ethanol solvent replacement, atmospheric drying and ball milling pulverization. Compared with water bath and hydrothermal method, microwave hydrothermal treatment had higher heating efficiency to form egg white hydrogel (EWH). Ethanol solvent exchange reduced the surface tension from water evaporation, allowing the porous structure of EWH to be maintained during atmospheric pressure drying, while EWH structure collapsed without solvent exchange. Ball milling made EWM present smaller particle size and higher specific surface area than common pulverization, owing excellent oil holding ability (1.24 ± 0.04 g/g) and great ability to form networks in oil. Compared to control oleogel based on microgel without solvent exchange or by common pulverization, EWM oleogel showed higher viscosity and gelatinability, which was beneficial to the improvement of oxidation stability. This oleogel can be further used as the solid fat alternative or bioactive substance delivery carriers in food industry.

Mesenchymal Stem Cell‐Laden Composite β Cell Porous Microgel for Diabetes Treatment

AbstractType 1 diabetes mellitus is a chronic metabolic condition characterized by the autoimmune damage of pancreatic β cells. As an alternative to continuous exogenous insulin administration of insulin, β cell transplantation is shown to provide an alternative approach for controlling hyperglycemia in diabetes. However, β cell transplantation faces significant challenges of low β cell proliferation and immunologic insults. Thus, novel approaches capable of promoting the islet microenvironment for sustainability is highly desired. This study develops mesenchymal stem cell (MSC)‐laden composite β cell porous microgels (MGs) to address sustainability for the treatment of diabetes. The MGs are prepared via microfluidic droplet templates encapsulating both MSCs and β cells with porogen for creating a porous structure. In addition to offering a suitable microenvironment for nutrient delivery, the porous structure promoted β cell growth and insulin secretion. The outstanding anti‐apoptotic and immunomodulatory roles of MSCs further provide a favorable environment for β cell survival and function. On this basis, the therapeutic performance of the MGs in reducing hyperglycemia and achieving sustained glycemic control in diabetic mice is demonstrated. Collectively, these results show that the novel MGs have great potential for the treatment of diabetes providing a promising platform for clinical β cell transplantation.

Preparation of microgel co-loaded with nuciferine and epigallocatechin-3-gallate for the regulation of lipid metabolism.

This study aims to enhance the stability and bioavailability of nuciferine (NF) and epigallocatechin-3-gallate (EGCG) by loading NF into liposomes and then incorporating the liposomes and EGCG into porous microgels (NFEG-microgel) prepared with chitosan and proanthocyanidin. Analysis of particle size (0.5-3.0 μm), electron microscopy, rheology, stability, and simulated gastrointestinal release confirmed that the prepared microgels had high encapsulation rate and good stability and release characteristics. Intervention experiments were performed by orally administering NFEG-microgel to high-fat diet rats to evaluate its efficacy and regulatory mechanism for blood lipid metabolism. NFEG-microgel intervention significantly reduced the body weight and serum lipid level, and the mechanism was related to the expression regulation of key genes involved in lipid metabolism and miRNAs (miR-126a-5p and miR-30b-5p) in serum extracellular vesicles. In addition, NFEG-microgel improved the diversity of gut microbiota by enriching short-chain fatty acids (SCFA)-producing bacteria and reducing harmful bacteria, suggesting that it can ameliorate lipid metabolism by regulating the intestinal flora community in rats.

One‐Step Generation of Porous GelMA Microgels by Droplet‐Based Chaotic Advection Effect

AbstractPorous GelMA microgels are promising scaffolds for biomedical research and regenerative medicine due to their special topology, cell‐loading capacity, and high biocompatibility. However, the traditional preparation of porous microgels is often limited by some complex postprocessing processes such as freeze‐drying and swelling equilibrium. Herein, we present a simple strategy for in situ generation of porous GelMA microgels as cell carriers by integrating the placeholder of polyethylene oxide (PEO) and chaotic advection effect of droplets in microfluidic devices. The device is mainly composed of four functional units, including droplet generation, rapid mixing, photopolymerization, and collection. The strategy allows precise control of the size and porosity of the microgels by changing the flow rates of the continuous and dispersed phases. Furthermore, both human mesenchymal stem cells (hMSCs) and umbilical vein endothelial cells (HUVECs) cultured on the surface of obtained microgels show high cell viability, spreading, and proliferation, which indicate their good biocompatibility and potential as microcarriers for various cell types. The proposed strategy provides a novel approach for the preparation of porous microgels holding promise in tissue engineering and scalable cell expansion.

4D Printing of Extrudable and Degradable Poly(Ethylene Glycol) Microgel Scaffolds for Multidimensional Cell Culture.

Granular synthetic hydrogels are useful bioinks for their compatibility with a variety of chemistries, affording printable, stimuli-responsive scaffolds with programmable structure and function. Additive manufacturing of microscale hydrogels, or microgels, allows for the fabrication of large cellularized constructs with percolating interstitial space, providing a platform for tissue engineering at length scales that are inaccessible by bulk encapsulation where transport of media and other biological factors are limited by scaffold density. Herein, synthetic microgels with varying degrees of degradability are prepared with diameters on the order of hundreds of microns by submerged electrospray and UV photopolymerization. Porous microgel scaffolds are assembled by particle jamming and extrusion printing, and semi-orthogonal chemical cues are utilized to tune the void fraction in printed scaffolds in a logic-gated manner. Scaffolds with different void fractions are easily cellularized post printing and microgels can be directly annealed into cell-laden structures. Finally, high-throughput direct encapsulation of cells within printable microgels is demonstrated, enabling large-scale 3D culture in a macroporous biomaterial. This approach provides unprecedented spatiotemporal control over the properties of printed microporous annealed particle scaffolds for 2.5D and 3D tissue culture.

Studies on interfacial properties of microgels and their application for food emulsions and foams

Many liquid-type food products exist either partially or wholly as an emulsion and a foam. In such systems, mixed states at the beginning and prevention of subsequent time-dependent changes are usually significant for quality management. In this research, as an intermediate material between traditional emulsifier molecules and solid particles, fine soft particles, i.e. microgels obtained from milled rice, soybean protein isolate, and polysaccharides were examined. Studies on the emulsifying properties of gelatinized rice flour, the enhanced technological functionality of soybean protein isolate via microgelation on emulsification and foaming, and the impartation of emulsifying ability to surface-inactive polysaccharides were reviewed to present the usefulness of the microgels in food emulsions and foams. In addition, interfacial properties of soft and porous microgels were summarized to promote their future application in practical food products in emulsified and foamed states.

Pearl-inspired graphene oxide-collagen microgel with multi-layer mineralization through microarray chips for bone defect repair.

Biomineralization of natural polymers in simulated body fluid (SBF) can significantly improve its biocompatibility, osteoconductivity, and osteoinductivity because of the hydroxyapatite (HAp) deposition. Nevertheless, the superficial HAp crystal deposition hamper the deep inorganic ions exchange in porous microgels, thus gradually leading to a nonuniform regeneration effect. Inspired by the pearl forming process, this article uses the microarray chips to fabricate the multi-layer mineralized graphene oxide (GO)-collagen (Col)-hydroxyapatite (HAp) microgel, denoted as MMGCH. These fabricated MMGCH microgels exhibit porous structure and uniform HAp distribution. Furthermore, the suitable microenvironment offered by microgel promotes the time-dependent proliferation and osteogenic differentiation of stem cells, which resulted in upregulated osteogenesis-related genes and proteins, such as alkaline phosphatase, osteocalcin, and collagen-1. Finally, the MMGCH microgels possess favorable bone regeneration capacities both in cranial bone defects and mandibular bone defects via providing a suitable microenvironment for host-derived cells to form new bone tissues. This work presents a biomimetic means aiming to achieve full-thickness and uniform HAp deposition in hydrogel for bone defect repair.

Stem Cell‐Recruiting Injectable Microgels for Repairing Osteoarthritis (Adv. Funct. Mater. 48/2021)

Injectable Microgels Inspired by the phenomenon where islands could recruit seabirds for nesting, in article number 2105084, Xiaoji Luo, Wenguo Cui, Wei Huang, and co-workers present an injectable porous microgel generated via microfluidic technology that is non-covalently loaded with PDGF-BB and TGF-β3, forming “cell island” microgels that can serve as a temporary “nest site” to recruit endogenous stem cells and presents a promising therapeutic effect for osteoarthritic cartilage damage.

3D printed porous microgel for lung cancer cells culture in vitro

Currently, in vitro cancer cell culture technology is very important for cancer research. Existing studies have shown that two-dimensional (2D) cell environment may cause significant differences from tumor cells in vivo, resulting in high failure rates when the therapies developed in 2D tumor models translated to the clinic. And compared with 2D culture, the isotropic three-dimensional (3D) culture can construct an environment more similar to that in the body. Here, we utilized 3D printed porous microgel to culture for lung cancer cell and also explored possible mechanism of how 3D culture environment regulates actin cytoskeleton. Compared with 2D cultured lung cancer cells, cells in porous microgel are more similar to those extracted from the existing gold standard: mouse transplanted tumors, in terms of the ROCK-actin pathway. In addition, this study also revealed that ROCK pathway altered by environment played an important role in regulating the drug sensitivity of lung cancer cells. Hence, this 3D printed porous microgel is a promising lung cancer cell culture method, which shows potentional application in future cancer research and drug development.

Synthesis of porous starch microgels for the encapsulation, delivery and stabilization of anthocyanins

A novel pH/salt-responsive porous microgel was developed from hydrolyzed oxidized starch for the encapsulation, delivery, and stabilization of anthocyanins. To synthesize this microgel, native corn starch was modified by sequential TEMPO oxidation and glucoamylase hydrolysis, using trisodium phosphate (STMP) as a cross-linker. The morphology, structure, and physical properties of the modified starch samples and microgels were characterized by SEM, ATR-FTIR, and particle size analyses, as well as by zeta-potential measurements. The obtained results indicate that compared to the oxidized microgels, the porous microgels exhibit higher capacity of anthocyanin loading and slower release. A pH of 3 is least favorable for the loading of anthocyanins into the microgels and 22.7% of the encapsulated anthocyanins are released from oxidized microgels, compared to 10.4% released from porous microgels. In addition, the porous microgels enhance the stability of anthocyanins, which facilitates storage. The residual rate of anthocyanins encapsulated in porous microgels is around 31%, whereas that of compounds in oxidized microgels approaches 18% after 30 d of storage. • A novel pH/salt-responsive porous microgel was developed from hydrolyzed oxidized starch. • The adsorption, delivery and stabilization of anthocyanins were investigated. • The porous microgels exhibit higher capacity of anthocyanin loading and slower release.

Hierarchical Porous Polymers via a Microgel Intermediate: Green Synthesis and Applications toward the Removal of Pollutants

Exploring a synthetic approach to prepare processable hierarchical porous polymers (PPs) is challenging. In the article, a strategic approach is presented, where polymerization (hyperbranching)-induced self-assembly in water leads to the formation of porous microgels (containing both micropores and mesopores), which is followed by spontaneous cross-linking of those intermediate microgels, leading to the formation of PPs. The synthetic process involves simple and green reactions. During this process, hydrophobicity of chosen monomers controls the morphology and porosity of the microgel, which in turn dictates the hierarchical porous morphology of the PPs. Such a synthetic hierarchy during the PP formation in water ensures increase of both surface area and active functionalities among different prototypes. Furthermore, under right conditions, the microgel-based emulsion can be used to form homogeneous porous thin films (average thickness 2–10 nm), which is important in the context of processability of such polymers. The synthesized hierarchical PPs have excellent adsorption capacities for different pollutants, such as iodine (3020 mg/g), methyl orange (1571 mg/g), congo red (1125 mg/g), and high CO2 uptake capacity with good selectivity.

Programming Hydrogen Production via Controllable Emulsification/Demulsification in a Switchable Oil–Water System

Compositing stimuli-responsive polymers or microgels can provide material systems with the unique capability of being programmable under specific external signals. Herein we show that by using CO2-responsive microgels as carriers of metal nanocatalysts and stabilizers to disperse the immiscible liquid organic hydrogen carriers (LOHCs), organosilanes in water coreagents, we can achieve a programmable generation of hydrogen for safe and portable applications of hydrogen fuels. The solubility of the tertiary amine-based microgel particles in water can be switched through CO2 bubbling or vacuuming, allowing a controllable demulsification or emulsification of the LOHCs/water system. Microcompartments consisting of a porous microgel shell with nanocatalysts and organosilane droplets can be broken and created on demand, resulting in a change of the oil/water interfacial area of over 3 orders of magnitude and a hydrogen generation rate increase of about 20-fold by forming the microcompartments. In addition, it wa...

Injectable Stem Cell Laden Open Porous Microgels That Favor Adipogenesis: In Vitro and in Vivo Evaluation.

Microgels, with large surface area per volume, show great advantages in adipose tissue engineering due to their injectability and similarity with natural extracellular matrix. However, to date, no studies have tried applying microgels to adipose tissue regeneration. Herein, based on double-bonded poly(l-glutamic acid)-g-2-hydroxyethyl methacrylate (PLGA-g-HEMA) and maleic anhydride-modified chitosan (MCS), an open porous microgel with high hydrophilicity and great injectability is successfully prepared (microgels diameters of 200-300 μm, pore diameter of 38 μm, and porosity of 88.3%). The storage modulus of 30 mg/mL of the microgel dispersions is 2000 Pa, which is similar to that of the native adipose tissue. The spheroidal stem cell shape and extensive cell-cell connections can be formed in the present microgels to promote adipogenic differentiation and realize adipose tissue regeneration. After injection in vitro, the microgels can maintain high stem cell viability up to 14 days. The extensive Oil red O staining is observed after adipogenic induction for 14 days. After 12 weeks postimplantation, adipose tissues can be regenerated well. Blood vessels are formed in the neogenerated tissues. The degradation rate of microgels roughly matches with the adipose tissue formation rate. The study offers an applicable microgel system to boost the adipose tissue regeneration.

Development of thermosensitive microgel-loaded cotton fabric for controlled drug release

COS-g-PVCL copolymer was synthesized and infiltrated into CaCO3 particles to prepare thermosensitive porous microgels which exhibited phase transition behavior at the temperature that was similar to the lower critical solution temperature(LCST) of copolymer. The incorporation of microgel to cotton was done by pad-dry-cure method from aqueous microparticle dispersion that contained citric acid as a crosslinking agent. In vitro drug release experiments were performed at two different temperatures (25 and 37°C) in PBS of pH 7.4 to study its drug release behavior with response to temperature. Due to the shrinkage of microgels, drug release profiles obtained were found to have enhanced release for aloin when the temperature was above LCST than other release conditions. Microgel-loaded fabrics proved to be in vivo biocompatible by skin irritation studies and displayed an obviously high water vapor permeability at 40°C. The MTT assay showed no obvious cytotoxicity of microgel-loaded cotton against mouse fibroblast cells within 5days. The results obtained demonstrated the potential use of the thermos-responsive microgel-loaded cotton fabrics as a textile-based drug delivery system for treating sunburn or skin care.

On-chip porous microgel generation for microfluidic enhanced VEGF detection.

Advances in medical diagnostics and personalized therapy require sensitive and rapid measurement of minute amounts of proteins from patients. Standard ELISA is difficult to prepare and involves lengthy protocols. Here we report a novel method using capture antibody immobilized porous poly (ethylene) glycol diacrylate (PEGDA) hydrogel microspheres to enable high sensitivity VEGF detection in arrayed microfluidics. Our technique incorporates antibody encapsulation, trapping, and flow perfusion on a single device. We showed that the convergence of tunable porous hydrogel with efficient microfluidics improved the sensitivity of the assay. The detection limit of this microfluidic porous microgel based assay was 0.9 pg/mL, with only 1+ hour of assay time, demonstrating a novel assay that exceeded conventional technologies in terms of sensitivity and speed.