Selenium-silk microgels as antifungal and antibacterial agents.

Antimicrobial resistance is a leading threat to global health. Alternative therapeutics to combat the rise in drug-resistant strains of bacteria and fungi are thus needed, but the development of new classes of small molecule therapeutics has remained challenging. Here, we explore an orthogonal approach and address this issue by synthesising micro-scale, protein colloidal particles that possess potent antimicrobial properties. We describe an approach for forming silk-based microgels that contain selenium nanoparticles embedded within the protein scaffold. We demonstrate that these materials have both antibacterial and antifungal properties while, crucially, also remaining highly biocompatible with mammalian cell lines. By combing the nanoparticles with silk, the protein microgel is able to fulfill two critical functions; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while simultaneously serving as a carrier for microbial eradication. Furthermore, since the antimicrobial activity originates from physical contact, bacteria and fungi are unlikely to develop resistance to our hybrid biomaterials, which remains a critical issue with current antibiotic and antifungal treatments. Therefore, taken together, these results provide the basis for innovative antimicrobial materials that can target drug-resistant microbial infections.

Modulating in vitro fecal fermentation behavior of sodium alginate by Ca2+ cross-linking.

Slow fermentable dietary fibers can be utilized by human gut microbiota in the distal region of the colon and thus exert a sufficient short-chain fatty acids (SCFAs) supplement in the distal region of the human colon. Alginate (Alg) based microgels are widely fabricated and used to control their digestion by digestive enzymes releasing active substances site-specifically. Herein, sodium alginate microgels with gradient calcium-ion (Ca2+) cross-linking densities were developed, restricting their degradation by gut microbiota. Alg microgels were prepared using high-speed shearing after Alg was cross-linked with 10, 40, and 60 mmol/L Ca2+, respectively (named 10-Alg, 40-Alg, and 60-Alg). The fluorescence and atomic force microscopic results showed that the 40-Alg particle has the densest structure among the three cross-linked Alg. In vitro human fecal fermentation results revealed that the Ca2+ cross-linking exerted more restricting effects than delaying effects on the fermentation of Alg, and the 40-Alg exhibited the slowest fermentation rate and the least fermentation extent, by characterizing the residual total carbohydrate content, residual monosaccharide content, pH, and total short-chain fatty acids. The 16S rRNA gene sequencing results indicated that cross-linking structures shaped a high specifical Bacteroides-type microbial community and that OTU205 (Bacteroides_xylanisolvens) highly correlated to the cross-linking density (R = 0.65, p = 0.047). In sum, Ca2+ cross-linking generated a dense and compact structure of sodium alginate that facilitated a more restricted fermentation property and specificity-targeting microbial community structure in comparison to the original sodium alginate.

Oral delivery of porous starch-loaded bilayer microgels for controlled drug delivery and treatment of ulcerative colitis.

We prepared one type of bilayer microgels for oral administration with three effects: pH responsiveness, time lag, and colon enzyme degradation. Combined with the dual biological effects of curcumin (Cur) for reducing inflammation and promoting repair of colonic mucosal injury, targeted colonic localization and release of Cur according to the colonic microenvironment were enhanced. The inner core, derived from guar gum and low-methoxyl pectin, afforded colonic adhesion and degradation behavior; the outer layer, modified by alginate and chitosan via polyelectrolyte interaction, achieved colonic localization. The porous starch (PS)-mediated strong adsorption allowed Cur loading in inner core to achieve a multifunctional delivery system. In vitro, the formulations exhibited good bioresponses at different pH conditions, potentially delaying Cur release in the upper gastrointestinal tract. In vivo, dextran sulfate sodium-induced ulcerative colitis (UC) symptoms were significantly alleviated after oral administration, accompanied by reduced levels of inflammatory factors. The formulations facilitated colonic delivery, allowing Cur accumulation in colonic tissue. Moreover, the formulations could alter gut microbiota composition in mice. During Cur delivery, each formulation increased species richness, decreased pathogenic bacterial content, and afforded synergistic effects against UC. These PS-loaded bilayer microgels, exhibiting excellent biocompatibility, multi-bioresponsiveness, and colon targeting, could be beneficial in UC therapy, allowing development into a novel oral formulation.

Effect of oil phases on the stability of myofibrillar protein microgel particles stabilized Pickering emulsions: The leading role of viscosity.

The Pickering emulsion may be restricted in the foods owing to the unreasonable use of oils. Herein, the effect of different oil phases on the stability of myofibrillar protein microgel particles stabilized Pickering emulsions was investigated. Results showed sunflower oil Pickering emulsions with high stability have the smallest droplet size (-26.17 µm). While peanut oil Pickering emulsions have the largest droplet size (-77.00 µm) and poor emulsion stability. The fatty acid analysis showed sunflower oil had low content of saturated (15.68 %) and super-long-chain (0) fatty acids, while peanut oil had high content of saturated (23.67 %) and super-long-chain (9.02 %) fatty acids, leading to a difference in viscosity. Low viscosity was more conducive to dispersing oil droplets and inhibiting the floating and gathering of droplets, thus enhancing the emulsion stability. Therefore, the oil with low content of super-long-chain and saturated fatty acids could be suitable for preparing MMP Pickering emulsions.

Engineering of an Osteoinductive and Growth Factor-Free Injectable Bone-Like Microgel for Bone Regeneration.

Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. Bone morphogenetic protein-loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes. This highlights the need to develop biomaterials that closely approximate the structure and composition of bone autografts, which are inherently osteoinductive and biologically active with embedded living cells, without the need for added supplements. Here, injectable growth factor-free bone-like tissue constructs are developed, that closely approximate the cellular, structural, and chemical composition of bone autografts. It is demonstrated that these micro-constructs are inherently osteogenic, and demonstrate the ability to stimulate mineralized tissue formation and regenerate bone in critical-sized defects in-vivo. Furthermore, the mechanisms that allow human mesenchymal stem cells (hMSCs) to be highly osteogenic in these constructs, despite the lack of osteoinductive supplements, are assessed, whereby Yes activated protein (YAP) nuclear localization and adenosine signaling appear to regulate osteogenic cell differentiation. The findings represent a step toward a new class of minimally invasive, injectable, and inherently osteoinductive scaffolds, which are regenerative by virtue of their ability to mimic the tissue cellular and extracellular microenvironment, thus showing promise for clinical applications in regenerative engineering.

Engineering dual-stimuli responsive poly(vinyl alcohol) nanofibrous membranes for cancer treatment by magnetic hyperthermia.

The development of new cancer treatment options, such as multifunctional devices, allows for a more personalized treatment, avoiding the known severe side effects of conventional options. In this context, on-demand drug delivery systems can actively control the rate of drug release offering a precise control of treatment. Magnetically and thermally controlled drug delivery systems have been explored as on-demand devices to treat chronic diseases and cancer tumors. In the present work, dual-stimuli responsive systems were developed by incorporating Fe3O4 magnetic nanoparticles (NPs) and poly(N-isopropylacrylamide) (PNIPAAm) microgels into electrospun polymeric fibers for application in cancer treatment. First, Fe3O4 NPs with an average diameter of 8 nm were synthesized by chemical precipitation technique and stabilized with dimercaptosuccinic acid (DMSA) or oleic acid (OA). PNIPAAm microgels were synthesized by surfactant-free emulsion polymerization (SFEP). Poly(vinyl alcohol) (PVA) was used as a fiber template originating fibers with an average diameter of 179 ± 14 nm. Stress tests of the membranes showed that incorporating both microgels and Fe3O4 NPs in electrospun fibers increases their Young's modulus. Swelling assays indicate that PVA membranes have a swelling ratio of around 3.4 (g/g) and that the presence of microgels does not affect its swelling ability. However, with the incorporation of Fe3O4 NPs, the swelling ratio of the membranes decreases. Magnetic hyperthermia assays show that a higher concentration of NPs leads to a higher heating ability. The composite membrane with the most promising results is the one incorporated with DMSA-coated NPs, since it shows the highest temperature variation, 5.1 °C. To assess the membranes biocompatibility and ability to promote cell proliferation, indirect and direct contact cell viability assays were performed, as well as cell adhesion assays. Following an extract method viability assay, all membrane designs did not reveal cytotoxic effects on dermal fibroblasts and melanoma cancer cells, after 48 h exposure and support long-term viability. The present work demonstrates the potential of dual-stimuli composite membranes for magnetic hyperthermia and may in the future be used as an alternative cancer treatment particularly in anatomically reachable solid tumors.

3D-printed microgels supplemented with dentin matrix molecules as a novel biomaterial for direct pulp capping.

OBJECTIVES: To develop a 3D-printed, microparticulate hydrogel supplemented with dentin matrix molecules (DMM) as a novel regenerative strategy for dental pulp capping. MATERIALS AND METHODS: Gelatin methacryloyl microgels (7% w/v) mixed with varying concentrations of DMM were printed using a digital light projection 3D printer and lyophilized for 2 days. The release profile of the DMM-loaded microgels was measured using a bicinchoninic acid assay. Next, dental pulp exposure defects were created in maxillary first molars of Wistar rats. The exposures were randomly capped with (1) inert material - negative control, (2) microgels, (3) microgels + DMM 500 µg/ml, (4) microgels + DMM 1000 µg/ml, (5) microgels + platelet-derived growth factor (PDGF 10 ng/ml), or (6) MTA (n = 15/group). After 4 weeks, animals were euthanized, and treated molars were harvested and then processed to evaluate hard tissue deposition, pulp tissue organization, and blood vessel density. RESULTS: All the specimens from groups treated with microgel + 500 µg/ml, microgel + 1000 µg/ml, microgel + PDGF, and MTA showed the formation of organized pulp tissue, tertiary dentin, newly formed tubular and atubular dentin, and new blood vessel formation. Dentin bridge formation was greater and pulp necrosis was less in the microgel + DMM groups compared to MTA. CONCLUSIONS: The 3D-printed photocurable microgels doped with DMM exhibited favorable cellular and inflammatory pulp responses, and significantly more tertiary dentin deposition. CLINICAL RELEVANCE: 3D-printed microgel with DMM is a promising biomaterial for dentin and dental pulp regeneration in pulp capping procedures.

Synergic Thermo- and pH-Sensitive Hybrid Microgels Loaded with Fluorescent Dyes and Ultrasmall Gold Nanoparticles for Photoacoustic Imaging and Photothermal Therapy.

Smart microgels (µGels) made of polymeric particles doped with inorganic nanoparticles have emerged recently as promising multifunctional materials for nanomedicine applications. However, the synthesis of these hybrid materials is still a challenging task with the necessity to control several features, such as particle sizes and doping levels, in order to tailor their final properties in relation to the targeted application. We report herein an innovative modular strategy to achieve the rational design of well-defined and densely filled hybrid particles. It is based on the assembly of the different building blocks, i.e., µGels, dyes, and small gold nanoparticles (<4 nm), and the tuning of nanoparticle loading within the polymer matrix through successive incubation steps. The characterization of the final hybrid networks using UV-vis absorption, fluorescence, transmission electron microscopy, dynamic light scattering, and small-angle X-ray scattering revealed that they uniquely combine the properties of hydrogel particles, including high loading capacity and stimuli-responsive behavior, the photoluminescent properties of dyes (rhodamine 6G, methylene blue and cyanine 7.5), and the features of gold nanoparticle assembly. Interestingly, in response to pH and temperature stimuli, the smart hybrid µGels can shrink, leading to the aggregation of the gold nanoparticles trapped inside the polymer matrix. This stimuli-responsive behavior results in plasmon band broadening and red shift toward the near-infrared region (NIR), opening promising prospects in biomedical science. Particularly, the potential of these smart hybrid nanoplatforms for photoactivated hyperthermia, photoacoustic imaging, cellular internalization, intracellular imaging, and photothermal therapy was assessed, demonstrating well controlled multimodal opportunities for theranostics.

Oral delivery of curcumin via multi-bioresponsive polyvinyl alcohol and guar gum based double-membrane microgels for ulcerative colitis therapy.

Anti-inflammatory drugs for ulcerative colitis (UC) treatment should specifically penetrate and accumulate in the colon tissue. Herein, a multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded heterogeneous double-membrane microgels (CUR@microgels) for oral administration was fabricated in this study, in which the inner core was derived from polyvinyl alcohol (PVA) and guar gum (GG) and the outer gel was decoration with alginate and chitosan by polyelectrolyte interactions. The structure and morphology of microgels were characterized. In vitro, the formulation exhibited good bio-responses at different pH conditions and sustained-release properties in simulated colon fluid with a drug-release rate of 84.6 % over 34 h. With the assistance of the outlayer gels, the microgels effectively delayed the premature drug release of CUR in the upper gastrointestinal tract. In vivo studies revealed that CUR@microgels specifically accumulated in the colon tissue for 24 h, which suggest that the interlayer gels were apt to reach colon lesion. As expected, the oral administration of microgels remarkably alleviated the symptoms of UC and protected the colon tissue in DSS-induced UC mice. The above results indicated that these facilely fabricated microgels which exhibited excellent biocompatibility and multi-bioresponsive drug release, had an apparent effect on the treatment of UC, which represents a promising drug delivery strategy for CUR in a clinical application.

Pectin-based microgels for rheological modification in the dilute to concentrated regimes.

HYPOTHESIS: A novel range of microgel particles of different internal cross-linking densities can be created by covalently cross-linking sugar beet pectin (SBP) with the enzyme laccase and mechanically breaking down the subsequent parent hydrogels to sugar beet pectin microgels (SBPMG) via shearing. The bulk rheological properties of suspensions of the different SBPMG are expected to depend on the microgel morphology, elasticity (crosslinking density) and volume fraction respectively. EXPERIMENTS: The rheology of both dilute and concentrated dispersions of SBPMG were studied in detail via capillary viscometry and shear rheometry, supplemented by information on particle size and shape from static light scattering, confocal microscopy and electron microscopy. FINDINGS: For dilute suspensions of SBPMG, data for viscosity versus effective volume fraction (ɸeff) falls on a 'master' curve for all 3 types of SBPMG. In the more concentrated regime, the softer microgels allow greater packing and interpenetration and give lower viscosities at the same ɸeff, but all 3 types of microgel give much higher viscosities than the equivalent concentration of 'non-microgelled' pectin. The firmer microgels can be concentrated to achieve elasticities equivalent to the original parent hydrogel. All SBPMG suspensions were extremely shear thinning but showed virtually no time-dependence.

Ultrasonication, immune activity, and photocrosslinked microgel formation of pectic polysaccharide isolated from root bark of Ulmus davidiana var. japonica (Rehder) Nakai.

The root bark of Ulmus davidiana var. japonica (Rehder) Nakai (Japanese elm) has been used for inflammatory disease treatments. In this work, we isolated pectic polysaccharides from the root bark of U. davidiana (UDP) and explored the immune activities of intact and ultrasonicated UDP on human macrophages. The UDP-treated macrophages showed a proinflammatory response, indicating classical activation via Toll-like receptor-mediated recognition. For hydrogel formation, the ultrasonicated UDP was modified with methacrylate groups, then subjected to photocrosslinking. The formed bulk hydrogel was pulverized into microgels by homogenization, and the microgel size was modulated for macrophage phagocytosis. The UDP microgel-treated macrophages displayed microgel internalization and classical activation that involved upregulation of M1 polarization markers (IL6, TNF-α, and CCR7), indicating that the microgel can be used as a carrier for macrophage-targeted drug delivery.

Evaluation of alginate-biopolymers (protein, hydrocolloid, starch) composite microgels prepared by the spray aerosol technique as a carrier for green tea polyphenols.

Effects of low methoxyl pectin, milk protein concentrate (MPC), and waxy starch on the encapsulation of green tea-polyphenols in alginate gels produced using spray aerosol technique were evaluated. MPC and waxy starch treated first by cold-renneted induced gelation method and gelatinization method, respectively. DSC thermal analysis and FTIR spectroscopy were used to prove the presence of polyphenols in gel matrixes. The encapsulation efficiency (%EE) and the polyphenols release were investigated using Folin-Ciocalteu assay. The results showed that the addition of biopolymers into alginate gels increased the encapsulation efficiency (%EE) but reduced the release percentage of polyphenol in water and simulated gastric fluid (SGF). Among the three biopolymers, cold-renneted MPC gave the best protection for polyphenols encapsulated in alginate microgels. It increased %EE from 63% to 68% in fresh gels, reduced the release percentage in water from 72% to 62% and reduced the release percentage in SGF from 76% to 67%.

Emulsions stabilised with pectin-based microgels: investigations into the effect of pH and ionic strength on emulsion stability.

Pectin-based microgel particles (MGPs) are encouraging sustainable emulsifying agents for food-applications. Based on polyelectrolytes, pectin-based MGPs are assumed to be pH and ionic strength sensitive, in a similar manner to MGPs of synthetic polymers. Besides building a barrier around oil droplets, charged MGPs repulse each other. Thus the stabilisation mechanisms of pectin-based MGPs should be both steric and electrostatic. To investigate this, emulsions were homogenised with MGP concentrations ranging from 0.5 to 2 wt% MGPs. After emulsification, the pH of the emulsions was adjusted to 4, 3, or 2; and the resulting droplet sizes were measured. We found out that the droplet size and the appearance of agglomerates increased with decreasing pH values. This was caused by the loss of the MGP surface charge, as stated by their ζ-potential, showing an increase from -33.71 ± 4.1 mV for samples with pH 4 to -17 ± 0.6 mV, and -3.4 ± 0.6 mV for pH 3 and 2, respectively. However, the degree of coalescence was dependent on the MGP concentration, as samples with 0.5 wt% coalesced more readily than samples with 2 wt% MGP. These results help understand the emulsion stabilisation mechanisms of pectin-based MGPs and what effect formulation parameters have on the long-term stability of MGP-stabilised emulsions.

Microencapsulation of Lactobacillus casei and Lactobacillus rhamnosus in pectin and pectin-inulin microgel particles: Effect on bacterial survival under storage conditions.

The main objective of the research was to evaluate the performance of synbiotic delivery systems using pectin microgels on the protection of two probiotic strains (Lactobacillus casei ATCC 393 and Lactobacillus rhamnosus strain GG [ATCC 53103]) to simulated gastrointestinal digestion (GD) and storage conditions (4 ± 1 °C) in a 42 days trial. Microgel particles were prepared by ionotropic gelation method and three variables were evaluated: incubation time (24 and 48 h), free vs encapsulated cells, and presence or absence of prebiotic (commercial and Jerusalem artichoke inulin). Results demonstrated an encapsulation efficiency of 96 ± 4% into particles with a mean diameter between 56 and 118 µm. The viability of encapsulated cells after 42 days storage stayed above 7 log units, being encapsulated cells in pectin-inulin microgels more resistant to GD compared to non-encapsulated cells or without prebiotics. In all cases incubation time influenced the strains' survival.

Dermal toxicity, dermal irritation, and delayed contact sensitization evaluation of oil body linked oleosin-hEGF microgel emulsion via transdermal drug delivery for wound healing.

Objective: The expression of therapeutic proteins in plant oil body bioreactors has attracted much attention. But its safety is not yet clear. This article determines the risk of safety after using the drug. Methods: The oil body-linked oleosin-hEGF microgel emulsion (OBEME) was prepared by mixing the xanthan gum with suitable concentrations in an appropriate proportion. Skin irritation and sensitization reaction were investigated in rats and guinea pigs using OBEME as test article.Results: The OBEME did not produce dermal erythema/eschar or oedema responses. The dermal subacute and subchronic toxicity of OBEME were evaluated in accordance with OECD guidelines. Compared with the control group, the basic physical signs, such as weight, feed, drinking, excretion, and behaviour of experimental animals, were not abnormal. In addition, no abnormality was found in haematological parameters, biochemical indexes, relative organ weight, and histopathological observation of organs, and there was no significant difference compared with normal saline treatment group. Therefore, we conclude that OBEME has no toxic effects and is safe and reliable to be used for topical application.

Structure-Activity-Relationship Studies to Elucidate Sources of Antibacterial Activity of Modular Polyacrylate Microgels.

Emerging infections of unknown origin and increasing bacterial resistance against available antibiotics necessitate the development of different antimicrobial agents with unconventional mechanisms of action. A promising strategy to meet this need may be found by combining polymeric scaffolds with transition metals, e.g., by decorating polyacrylate-based microgels with Cu(II) complexes. A series of structure-activity relationship studies using broth microdilution assays with such materials and Staphylococcus aureus concluded that the antimicrobial activity of microgels can be tailored during their synthesis by choice of co-monomers, by design of the binding strength between Cu(II) ions and backbone ligands, and by selection of the counter ions for coordination to the metal complexes. A microgel Cu2LP(EG) (L = VBbsdpo) with an optimized minimal inhibitory concentration of 0.39 ± 0.03 µg/mL is thereby derived and synthesized from 60 mol % of cross-linking ethylene glycol dimethacrylate, 40 mol % butyl acrylate, 0.5 mol % VBbsdpo ligand with 1 mol % Cu(II) ions, and 5 mol % ethylene glycol as counter ions. The antimicrobial activity of the microgel has a lifetime of over 18 months at ambient temperature. Bactericidal activity of the same microgel is observed by replating assays in less than 15 min when exposing S. aureus to microgel concentrations of 1.5-fold of its minimum inhibitory concentration (MIC) value or higher. Furthermore, spectrophotometric evaluations at 260 nm revealed time- and concentration-dependent release of intracellular bacterial components after interactions with the microgel indicating irreversible damage to the bacterial cell membrane as a possible mechanism of activity. Preliminary results indicate that the selected microgels are not cytotoxic toward human dermal fibroblasts at MIC value concentrations for over 20 h.

Emulsion-filled hydrogels for food applications: influence of pH on emulsion stability and a coating on microgel protection.

Encapsulation structures for oral administration have been widely employed by the food, personal care, and pharmaceutical industries. Emulsion-filled microgels can be used to encapsulate bioactive compounds, allowing the entrapment of lipid droplets in biopolymer networks and promoting bioactive protection. The influence of pH and biopolymer concentration on the formation and structure of emulsions was evaluated, allowing the production of emulsion-filled hydrogels with potato starch as the main compound, a low alginate concentration, and gelatin in the continuous phase. Potato starch was used because it is generally recognized as safe (GRAS) and has phosphate groups, which allow electrostatic interactions with biopolymers and provide resistance to the network. Emulsion stability was achieved at pH 6, while complexation was verified under acidic conditions, which made the ionic gelation process unfeasible for the production of microgels. After defining the pH for emulsion production, microgels were formed by ionic gelation and coated microgels by electrostatic interactions, as evidenced by quartz crystal microbalance. The alginate and gelatin coating did not affect the morphology of the microparticles. An in vitro digestion assay showed that microgels composed mainly of potato starch were not degraded in the simulated mouth step. The coating layer provided extra microgel protection during digestion, demonstrating the ability of encapsulation systems to promote targeted delivery of bioactive compounds.

Deciphering the Structural Network That Confers Stability to High Internal Phase Pickering Emulsions by Cross-Linked Soy Protein Microgels and Their In Vitro Digestion Profiles.

High internal phase Pickering emulsions (HIPPEs) stabilized by food-grade particles have received much attention in recent years. However, the stabilizing mechanism (e.g., structural network) in the continuous phase of HIPPEs stabilized by proteins is not well understood. In this work, we deciphered the stabilizing mechanisms that confer stability to HIPPEs produced from sunflower oil and soy protein microgels (SPMs). HIPPEs were fabricated at the protein concentrations of 1.50-2.00 wt % and oil volume fraction of 0.78-0.82. The cryo-scanning electron microscopy (cryo-SEM) observations indicated that there were two possible stabilizing mechanisms for HIPPEs at the protein concentrations of 1.50-2.00 wt %: the first is a stabilization provided by the shared monolayer of SPMs (at a protein concentration of 1.50%), and the other is stabilization provided by the distinct monolayer of SPMs (at protein concentrations of 1.75 and 2.00 wt %). The latter protein concentration created a thick network, formed by interacting SPMs, which trapped oil droplets. Results also confirmed that HIPPEs have an open-cell porous structure, forming a sponge-like morphology, where the internal phase was located. This study also investigated the digestibility of HIPPEs, suggesting a slower free fatty acid-releasing profile in in vitro intestinal digestion.

Influence of Chemical and Physical Change of Pollen Microgels on Swelling/De-Swelling Behavior.

Pollen, the male microgametophyte of seed plants, is commonly used as a food and health supplement. Here, a facile method to transform sunflower pollen into pH-responsive microgels with tailored properties is presented. The structure and morphology of the pollen microgel are characterized by scanning electron microscopy, confocal laser scanning microscopy, and dynamic image particle analysis based on potassium hydroxide treatment with various incubation time and concentration. These pollen microgels exhibit significant volume change under different pH conditions and Ca+ /ethylenediaminetetraacetic acid treatment. The results describe the fundamental properties of pollen microgels and pave the way for its future applications, such as "smart" drug carriers.

Near-infrared triggered on-demand local anesthesia using a jammed microgels system.

To conveniently modulate the degree of local analgesia in response to changes in patients' needs and level of activity, a NIR-activated drug delivery system based on jammed microgels was introduced in the present study to realize on-demand local anesthesia. Chemically cross-linked gelatin microgels (5-15 µm) containing N-isopropylacrylamide (NIPAM), methylallyl polyethylene glycol (APEG) and graphene oxide (GOs) were fabricated through emulsion. After the in situ free radical polymerization, the physical network was formed, producing microgels with double networks (DN microgels). The DN microgels exhibited thermosensitive properties. The copolymerization of APEG resulted in the increase of lower critical solution temperature (LCST) of microgels. The maximum volume shrinkage ratio of DN microgels (NIPAM40 + APEG60) increased with the increase of the content of physical cross-linking network. The DN microgels also exhibited NIR-responsive ability. Under the NIR irradiance of 272 mW/cm2, the temperature of DN microgels with 3 mg/mL GOs reached 40 °C within 60 s, resulting in the volume shrinkage of 14%. Ropivacaine release from DN microgels could be effectively triggered by NIR irradiation in vitro. After centrifugation, a jammed microgels system was produced where microgels packed densely, displaying shear-thinning behavior for achieving injection. The jammed DN microgels carrying ropivacaine were injected subcutaneously into rat footpad. NIR irradiation produced on-demand and repeated infiltration anesthesia in the rat footpad. The jammed DN microgels system thus was beneficial in the management of pain.