Microgel Research Articles

Structural, physicochemical, and in vitro digestion properties of microgel-reinforced synbiotic hydrogel beads filled with pectic oligosaccharides as a delivery system for Limosilactobacillus reuteri

Pea protein microgel (MG)-reinforced synbiotic low methoxyl pectin (LMP) hydrogel beads filled with different concentrations (0 %, 0.2 %, and 0.4 %) of pectic oligosaccharides (POS) were developed as a delivery system for Limosilactobacillus reuteri (L. reuteri). SEM results revealed that incorporating POS into the hydrogel beads made the gel matrix smoother and more compact, reducing probiotic leakage and higher encapsulation efficiency. FT-IR analysis observed new ionic crosslinking between LMP and calcium ions. In vitro digestion results suggested that MG-reinforced synbiotic hydrogel beads showed higher survival rates throughout the upper gastrointestinal tract than MG, and the highest values were observed in the hydrogel beads with 0.4 % of POS. Most L. reuteri was released from the developed system after exposure to simulated colonic conditions for 48 h. MG-reinforced synbiotic hydrogel beads showed higher thermal and storage stability than MG alone, indicating that adding hydrogel bead layer to MG can efficiently protect L. reuteri from environmental stresses.

Compartmentalized Polyampholyte Microgels by Depletion Flocculation and Coacervation of Nanogels in Emulsion Droplets.

In pH-responsive drug carriers, the distribution of charges has been proven to affect delivery efficiency but is difficult to control and verify. Herein, we fabricate polyampholyte nanogel-in-microgel colloids (NiM-C) and show that the arrangement of the nanogels (NG) can easily be manipulated by adapting synthesis conditions. Positively and negatively charged pH-responsive NG are synthesized by precipitation polymerization and labelled with different fluorescent dyes. The obtained NG are integrated into microgel (MG) networks by subsequent inverse emulsion polymerization in droplet-based microfluidics. By confocal laser scanning microscopy (CLSM), we verify that depending on NG concentration, pH value and ionic strength, NiM-C with different NG arrangements are obtained, including Janus-like phase-separation of NG, statistical distribution of NG, and core-shell arrangements. Our approach is a major step towards uptake and release of oppositely charged (drug) molecules.

4D Cell-Condensate Bioprinting.

4D bioprinting techniques that facilitate formation of shape-changing scaffold-free cell condensates with prescribed geometries have yet been demonstrated. Here, a simple 4D bioprinting approach is presented that enables formation of a shape-morphing cell condensate-laden bilayer system. The strategy produces scaffold-free cell condensates which morph over time into predefined complex shapes. Cell condensate-laden bilayers with specific geometries are readily fabricated by bioprinting technologies. The bilayers have tunable deformability and microgel (MG) degradation, enabling controllable morphological transformations and on-demand liberation of deformed cell condensates. With this system, large cell condensate-laden constructs with various complex shapes are obtained. As a proof-of-concept study, the formation of the letter "C"- and helix-shaped robust cartilage-like tissues differentiated from human mesenchymal stem cells (hMSCs) is demonstrated. This system brings about a versatile 4D bioprinting platform idea that is anticipated to broaden and facilitate the applications of cell condensation-based 4D bioprinting.

Tough and self‐healable carrageenan‐based double network microgels enhanced physical hydrogels for strain sensor

AbstractDouble network hydrogels (DN gels) demonstrate extremely high strength and toughness; however, conventional DN gels are fully chemically crosslinked, which are often softening and lack self‐healing. Here, a new type of fully physical DN (P‐DN) gels, that is, K+ ions crosslinked κ‐carrageenan (K+C) microgel (MG) composite hydrophobically crosslinked polyacrylamide (HPAAm) gels or K+C‐MG/HPAAm gels, in which the HPAAm gel was physically crosslinked by hydrophobic interactions as well as topologically crosslinked by P‐DN microgels, were prepared by a facile one‐pot method. At the optimal condition, K+C‐MG/HPAAm gel exhibited high strength (0.36 MPa) and high toughness (968 J/m2). In addition, it can rapidly recover from softening and display good fatigue resistance. Notably, K+C‐MG/HPAAm gel also demonstrated self‐healing properties on account of its physical nature. Because there are anionic κ‐carrageenan and KCl, K+C‐MG/HPAAm gels are ionic conductive, which were used as strain sensors to monitor the human motions. We believe our K+C‐MG/HPAAm gels provide a new insight in the field of DN gels.

Programmed Multiresponsive Hydrogel Assemblies with Light‐Tunable Mechanical Properties, Actuation, and Fluorescence

AbstractFabrication strategies for programmed hydrogels that provide precise spatial control with predetermined responses to external stimuli are highly desirable. In this study, a partially reversible light‐driven assembly (PRLDA) method is introduced to construct multiresponsive hydrogels utilizing microgel (MG) particle building blocks (swollen diameter of 107 nm). No other material is required to prepare the gels beyond the MGs themselves. Facile preparation of multiresponsive hydrogels that are reversibly responsive to light, pH, and temperature using phototriggered covalent interlinking of coumarin‐based MGs is demonstrated. The gels have phototuneable moduli and swelling ratios and show light‐assisted healing and reshaping. Remarkably, the intrinsic fluorescence of the gels undergoes a reversible light‐triggered wavelength‐shift. The emission peak blueshifted from 420 to 390 nm upon irradiation with 365 nm light. The PRLDA gels can be constructed using either positive or negative photopatterning. It is shown that the gels can be exploited for multiresponsive cytocompatible actuators, grippers, and ON/OFF circuit components as well as anticounterfeit gels. The PRLDA method provides new insight into programmed gel property control and has excellent potential for biomaterial and optoelectronic applications.

Core-Shell-Shell Nanoparticles for NIR Fluorescence Imaging and NRET Swelling Reporting of Injectable or Implantable Gels.

Injectable gels that support load are desirable for restoring the mechanical properties of degenerated load-bearing tissue. As these gels become increasingly sophisticated, the need to remotely image them and monitor their swelling increases. However, imaging such gels and monitoring their swelling using noninvasive means is challenging. Here, we use a very low concentration of near-infrared (NIR) core–shell–shell (CSS) reporter nanoparticles to both image and monitor swelling changes of two load-supporting gels. The load-supporting injectable gel consisted of covalently interlinked pH-responsive microgel (MG) particles. The latter gel was not cytotoxic and is termed a doubly cross-linked microgel (DX MG). Inclusion of a complementary fluorescent dye enabled ratiometric monitoring of gel swelling changes in response to pH via nonradiative resonance energy transfer (NRET). In addition, changes in the CSS nanoparticle emission intensity provided a NIR-only method that could also be used to monitor gel swelling. The gel was able to be imaged using NIR light, after being subcutaneously injected into a tissue model. To demonstrate versatility of our approach, CSS and the dye were included within a model implantable gel (poly(acrylamide/acrylic acid)) and fluorescent detection of swelling investigated. Because the concentrations of the reporting species were too low to affect the mechanical properties, our approach to remote gel imaging and swelling monitoring has good potential for application in injectable gels and implants.

In Situ Growth and Size Regulation of Single Gold Nanoparticles in Composite Microgels.

Herein, a novel method for the in situ growth of single gold nanoparticles (AuNPs) in microgel (MG) networks is presented. The key feature in this approach is the localization of β-diketone groups capable of both complexation and reduction of aurate ions in the MGs' core, which allows localization of the nucleation and growth of single AuNPs. The MG synthesis is carried out via precipitation polymerization in water with N-vinylcaprolactam as the main monomer and with the two comonomers acetoacetoxyethyl methacrylate (AAEM) and acrylic acid (AAc), where AAEM is mainly located in the MGs' core and AAc in their shell. For the synthesis of AuNPs, a certain amount of chloroauric acid (HAuCl4 ) is added to the dispersion, followed by fast reduction with sodium borohydride (NaBH4 ). In situ synthesized AuNPs in MGs possess a spherical shape, with a diameter of 8.1 ± 0.8 nm, being localized in the center of every MG. In addition, these AuNPs embedded into MG networks can be used as seeds that grow in their size after the addition of HAuCl4 up to 46.0 ± 9.5 nm under mild reaction conditions (room temperature, aqueous dispersion) and without the use of any additional reducing and stabilizing agents.

Kinetics of protopect in decomposition in vegetable raw material under high temperatures and pressures

The kinetics of the catalytic decomposition of protopectin (PP) of pomace, peach, pumpkin, citrus, rhubarb, sunflower heads (SH) and beet pulp in HCl solution at pH = 2.0 and T = 120 °C and pressure 1.5 atm. The decay products of PP are separated according to the previously developed method into fractions: microgel (MG), pectin substances (PS) and oligosaccharides (OS). The experimental data were processed on the basis of the idea of a parallel and successive irreversible chemical reaction of the first order, the rate constants for the decay of the PP into the corresponding components-MG, PS, and OS, were evaluated, conclusions were made about the advantages and disadvantages of the high-temperature process.

Switchable Supracolloidal Coassembly of Microgels Mediated by Host/Guest Interactions.

Supramolecular engineering of multibody colloidal systems provides flexible ways of manipulating superstructures and material properties. We investigate a coassembling microgel (MG) system, in which host- and guest-modified MG partners coassemble by molecular recognition, and show in detail how electrostatic repulsion needs to be balanced for the supramolecular recognition to take place. We observe a gradual change from repellent MGs to stable clusters and ordered flocculates upon decreasing electrostatic repulsion. The adaptive nature of the multivalent interactions embedded in the soft MG shell leads to kinetically trapped scenarios and fibril formation from spherical building blocks.

Catalytic Formation of Disulfide Bonds in Peptides by Molecularly Imprinted Microgels at Oil/Water Interfaces.

This work describes the preparation and investigation of molecularly imprinted polymer (MIP) microgel (MG) stabilized Pickering emulsions (PEs) for their ability to catalyze the formation of disulfide bonds in peptides at the O/W interface. The MIP MGs were synthesized via precipitation polymerization and a programmed initiator change strategy. The MIP MGs were characterized using DLS analysis, SEM measurement, and optical microscopy analysis. The dry and wet MIP MGs showed a hydrodynamic diameter of 100 and 280 nm, respectively. A template rebinding experiment showed that the MIP MGs bound over two times more template (24 mg g-1) compared to the uptake displayed by a nonimprinted reference polymer (NIP) MG (10 mg g-1) at saturation. Using the MIP MGs as stabilizers, catalytic oxidation systems were prepared by emulsifying the oil phase and water phase in the presence of different oxidizing agents. During the cyclization, the isolation of the thiol precursors and the oxidizing reagents nonselectively decreased the formation of the byproducts, while the imprinted cavities on the MIP MGs selectively promoted the intramolecular cyclization of peptides. When I2 was used as the oxidizing agent, the MIP-PE-I2 system showed a product yield of 50%, corresponding to a nearly 2-fold increase compared to that of the nonimprinted polymer NIP-PE-I2 system (26%). We believe the interfacial catalysis system presented in this work may offer significant benefits in synthetic peptide chemistry by raising productivity while suppressing the formation of byproducts.

Using click chemistry to dial up the modulus of doubly crosslinked microgels through precise control of microgel building block functionalisation

Vinyl functionalisation of poly(2-vinylpyridine-propargylacrylate) microgels via click chemistry gives hydrogels of inter-linked microgels with tuneable modulus values.

Swelling and mechanical properties of hydrogels composed of binary blends of inter-linked pH-responsive microgel particles.

We show that a new type of hydrogel can be prepared by covalently inter-linking binary blends of microgel (MG) particles and that the swelling ratio and modulus of the gels can be predicted from their composition. In previous work we established that physical gels of glycidyl methacrylate (GMA) functionalised poly(methyl methacrylate-co-methacrylic acid-co-ethyleneglycol dimethacrylate) microgel particles (GMA-MG) could be covalently inter-linked to give hydrogels, termed doubly crosslinked microgels, DX MGs. We build on this concept here by investigating the properties of DX MGs containing binary blends of GMA-MG particles and glycidyl oligo(ether ester) acrylate-functionalised microgel particles (GOE-MG). These new hydrogels were assembled by inter-linking nanoscale MG building blocks in the absence of small molecule monomers or crosslinkers. The volume fraction of GMA-MG particles used to prepare the GOE-GMA DX MGs was systematically varied. Rheology data showed that inclusion of GMA-MG and GOE-MG within the GOE-GMA DX MGs increased the modulus and yield strain, respectively, compared to the values measured for the respective physical gels. The data for the covalent GOE-GMA DX MG gels showed that the ductility increased with increasing GOE-MG content. GOE provided covalent inter-linking of the MG particles and also acted as a lubricant between particles due to its low Tg. By demonstrating compositionally determined swelling and mechanical properties for DX MG gels prepared using binary blends of MG particles, this study introduces a new, widely applicable, hydrogel construction assembly concept that is not available for conventional hydrogels.

A Study of Physical and Covalent Hydrogels Containing pH-Responsive Microgel Particles and Graphene Oxide

In this study we mixed low concentrations of graphene oxide (GO) with microgel (MG) particles and formed composite doubly cross-linked microgels (DX MG/GO) gels. The MG particles comprised poly(ethyl acrylate-co-methacrylic acid-co-1,4-butanediol diacrylate) with pendant glycidyl methacrylate units. The MG/GO mixed dispersions formed physical gels of singly cross-linked MGs (termed SX MG/GO), which were subsequently heated to produce DX MG/GO gels by free-radical reaction. The influence of the GO concentration on the mechanical properties of the SX MG/GO and DX MG/GO gels was investigated using dynamic rheology and static compression measurements. The SX MG/GO physical gels were injectable and moldable. The moduli for the DX MG/GO gels increased by a factor of 4-6 when only ca. 1.0 wt % of GO was included. The isostrain model was used to describe the variation of modulus with DX MG/GO composition. Inclusion of GO dramatically altered the stress dissipation and yielding mechanisms for the gels. GO acted as a high surface area, high modulus filler and played an increasing role in load distribution as the GO concentration increased. It is proposed that MG domains were dispersed within a percolated GO network. Comparison of the modulus data with those published for GO-free DX MGs showed that inclusion of GO provided an unprecedented rate of modulus increase with network volume fraction for this family of colloid gels. Furthermore, the DX MG/GO gels were biocompatible and the results imply that there may be future applications of these new systems as injectable load supporting gels for soft tissue repair.

Poly(vinylamine) microgel–dextran composite hydrogels: Characterisation; properties and pH-triggered degradation

The present study involves an investigation of the formation, characterisation and triggered-degradation of mixed dispersions involving cationic poly(vinylamine-co-bis(ethyl vinylamine) ether) (PVAM-BEVAME) microgel (MG) particles and partially oxidised dextran (Dexox). In this approach to colloidal hydrogel composite formation, imine bonds were formed by reaction between aldehyde groups of Dexox and the primary amine groups on the MG particles. The composite hydrogels contained MG particles that were externally cross-linked by Dexox to form an elastically effective network with high storage modulus (G′) values and low tanδ (=G″/G′, where G″ is the loss modulus) values. The G′ values for the MG–Dexox gels increased exponentially with increasing mass ratio (MR) of Dexox to MG. Interestingly, the yield strains determined from rheology also increased with MR and yield strains of up to 130% were measured. Au nanoparticles of comparable size to the Dexox chains adsorbed to the surface of the MG particles, which suggests that the pore size of the MG particles may have been smaller than that of the Dexox coils. The MG–Dexox gels were also subjected to acidic conditions to demonstrate pH-triggered gel network breakdown via imine bond cleavage. We show that new PVAM MG/aldehyde mixtures studied here for the first time form ductile and versatile colloidal gels and our new method provides a route to increasing ductility of hydrogels containing MG particles.

Physico‐Chemical Characterization of Pectic Polysaccharides from Various Sources Obtained by Steam Assisted Flash Extraction (SAFE)

AbstractPectic polysaccharides (PP) have been isolated from a variety of sources and characterized by their yield, anhydrogalacturonic (AGA) content, degree of methyl esterification (DE) and microgel (MG) content. Molar mass and mass distribution (MMD) were analyzed by high performance size‐exclusion chromatography (HPSEC) coupled with pressure differential viscosity (PDV) and differential refractive index (DRI) detectors. Results were grouped according to the DE of the PP. Among sources of lower methylated (LM) pectins, apricot pectin had the highest weight average molar mass (Mw) followed by apple pectin. Among high methylated (HM) pectins, pumpkin pectin had the highest value of Mw followed by tangerine and lemon pectins. All pectins studied were found to have bi‐modal distribution as indicated by their molar mass calibration curves. Apple pectin was the most polydisperse whereas pumpkin pectin was the least polydisperse as indicated by Mw/Mn, where Mn is the number average molar mass.