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Ischemic stroke, as a prevalent neurological disorder, often results in rapid increases in the production of reactive oxygen species (ROS) and inflammatory factors in the focal ischemic area. Though edaravone is an approved treatment, its effect is limited due to its weak ability to cross the blood-brain barrier (BBB) and short half-life. Other effective pharmacological treatment options are clearly lacking. In this study, PNIVDBrF-3-Eda (also named MG-3-Eda) was prepared using a thermo- and pH dual-responsive PNIVDBrF microgel. These were designed with a positively charged network, as synthesized by simultaneous quaternization cross-linking and surfactant-free emulsion copolymerization, to be loaded with the negatively charged edaravone. We then investigated whether such a targeted delivery of edaravone could provide enhanced neuroprotection. Cytotoxicity assays confirmed that the microgel (1 mg/mL) exhibited promising cytocompatibility with no remarkable effect on cell viability, cell cycle regulation, or apoptosis levels. In vitro and in vivo experiments demonstrated that the microgels could successfully penetrate the blood-brain barrier where efficient BBB crossing was observed after disruption of the BBB due to ischemic injury. This enabled MG-3-Eda to target the cerebral ischemic area and achieve local release of edaravone. Treatment with MG-3-Eda significantly reduced the cerebral infarct area in transient middle cerebral artery occlusion (tMCAO) mice and significantly improved behavioral scores. MG-3-Eda treatment also prevented the reduction in NF200 expression, a neuronal marker protein, and attenuated microglia activation (as detected by Iba1) in the local ischemic area via local antioxidant and anti-inflammatory effects. A superior neuroprotective effect was noted for MG-3-Eda compared to that for free edaravone. Our results indicate that MG-3-Eda administration represents a clear potential treatment for cerebral ischemia via its targeted delivery of edaravone to ischemic areas where it provides significant local antioxidant and anti-inflammatory effects.

The proposal of the aggregation-induced emission (AIE) effect shines a light on the practical application of luminescent materials. The AIE-active luminescence microgels (TPEC MGs) with photo-induced color-changing behavior were developed by integrating positively charged AIE luminogens (AIEgens) into the anionic network of microgels, where AIEgens of TPEC were obtained from the quaternization reaction between tetra-(4-pyridylphenyl)ethylene (TPE-4Py) and 7-(6-bromohexyloxy)-coumarin. The aqueous suspensions of TPEC MGs exhibit a significant AIE effect following the enhancement of quantum yield. In addition, further increase in fluorescence intensity and blueshift occur at elevated temperatures due to the collapse of microgels. The distinctive photochromic behavior of TPEC MGs was observed, which presents as the transition from orange-yellow to blue-green color under UV irradiation, which is different from TPEC in good organic solvents. The phenomenon of color changing can be ascribed to the competition between photodimerization of the coumarin part and photocyclization of TPE-4Py in TPEC. The photochromic TPEC MG aqueous suspensions can be conducted as aqueous microgel inks for information display, encryption, and dynamic anticounterfeiting.

Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms. Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness (P P P P P P Conclusion Our study suggested the potential therapeutic effects and the underlying mechanisms of HP-MSCs-HA on treating thin endometrium. HA hydrogel could be a preferable delivery method for HP-MSCs, and the strategy represents a promising therapeutic approach against endometrial injury in clinical settings. Graphical abstract

The fabrication of synthetic hydrogels, which simultaneously possess excellent mechanical properties and a high equilibrium water content (EWC) and can be potentially used to mimic the cartilage, o...

Thermosensitive fluorescent microgels (HMQC-MGs) were developed as selective and sensitive sensing systems for the detection of trace Fe3+ and Mn2+ ions in aqueous solutions. HMQC-MGs, which were s...

A receptive endometrium with proper thickness is essential for successful embryo implantation. However, endometrial injury caused by intrauterine procedures often leads to pathophysiological changes in its environment, resulting in subsequent female infertility. Among diverse treatment methods of endometrial injury, hydrogels are a class of hydrophilic three-dimensional polymeric network with biocompatibility as well as the capability of absorbing water and encapsulation, which have potential applications as a promising intrauterine controlled-release delivery system. This review summarizes recent advances in the approaches of endometrial repair and further focuses on the application of a hydrogel-based delivery system in endometrial repair, including its preparation, therapeutic loading considerations, clinical applications, as well as working mechanisms.

Poly(N-isopropylacrylamide) (PNIPAM)-tannic acid (TA) microgels were successfully prepared via surfactant-free emulsion polymerization (SFEP) at 70 °C in aqueous solution using N-isopropylacrylamide (NIPAM) as the monomer and a natural polyphenol macromolecule, TA, as the sole cross-linker. The cross-linking network of the PNIPAM-TA microgels was confirmed to contain both physical cross-linking structures formed via hydrogen-bonding interactions between TA and PNIPAM chains and chemical cross-linking structures formed via capturing the radicals of propagating polymer chains by catechol and pyrogallol groups of TA. Furthermore, TA was applied to modify the surface of hydrophobic Fe3O4 nanoparticles, leading to hydrophilic Fe3O4@TA composite nanoparticles, which were successfully used as the cross-linker to fabricate PNIPAM-Fe3O4@TA organic-inorganic hybrid microgels. The obtained PNIPAM-TA and PNIPAM-Fe3O4@TA organic-inorganic hybrid microgels had a uniform spherical shape with a relatively narrow size distribution and exhibited thermosensitive behavior and pH-tunable degradation. The PNIPAM-TA microgels were stable in the pH range of 1.3-11.1 but underwent complete degradation with pH above 11.4. The PNIPAM-Fe3O4@TA hybrid microgels were partially degraded at pH values of 1.3 and 2.1, stable in the pH range of 3.1-11.1, and underwent complete degradation at pH above 11.4. The partial degradation of PNIPAM-Fe3O4@TA organic-inorganic hybrid microgels under strong acidic conditions was attributed to the disintegration of Fe3O4 nanoparticles. The complete degradation of both microgels at pH above 11.4 was attributed to the hydrolysis of ester groups of TA under strong alkali conditions.

Background Wide applications of nanoparticles (NPs) have raised increasing concerns about safety to humans. Oxidative stress and inflammation are extensively investigated as mechanisms for NPs-induced toxicity. Autophagy and lysosomal dysfunction are emerging molecular mechanisms. Inhalation is one of the main pathways of exposing humans to NPs, which has been reported to induce severe pulmonary inflammation. However, the underlying mechanisms and, more specifically, the interplays of above-mentioned mechanisms in NPs-induced pulmonary inflammation are still largely obscure. Considered that NPs exposure in modern society is often unavoidable, it is highly desirable to develop effective strategies that could help to prevent nanomaterials-induced pulmonary inflammation. Results Pulmonary inflammation induced by intratracheal instillation of silica nanoparticles (SiNPs) in C57BL/6 mice was prevented by PJ34, a poly (ADP-ribose) polymerase (PARP) inhibitor. In human lung bronchial epithelial (BEAS-2B) cells, exposure to SiNPs reduced cell viability, and induced ROS generation, impairment in lysosome function and autophagic flux. Inhibition of ROS generation, PARP and TRPM2 channel suppressed SiNPs-induced lysosome impairment and autophagy dysfunction and consequent inflammatory responses. Consistently, SiNPs-induced pulmonary inflammation was prevented in TRPM2 deficient mice. Conclusion The ROS/PARP/TRPM2 signaling is critical in SiNPs-induced pulmonary inflammation, providing novel mechanistic insights into NPs-induced lung injury. Our study identifies TRPM2 channel as a new target for the development of preventive and therapeutic strategies to mitigate nanomaterials-induced lung inflammation. Graphical abstract

Of the multitude of stimuli-responsive microgels, it is still a challenge to achieve multiple responsivenesses to one single stimulus, which can even revert to the corresponding original state autonomously after stimulus. In this work, we reported a series of anthraquinone functionalized microgels (PNI

Enhanced phase separation and inverse order-to-order phase transition with increasing temperature was observed for a series of poly (acrylic acid)-b-poly (propylene oxide)-b-poly (acrylic acid) triblock copolymers with various block lengths by temperature-variable synchrotron small-angle X-ray scattering (SAXS). This abnormal phase behavior was attributed to the change of hydrogen (H)-bonding interaction in block copolymers upon increasing temperature and theoretically explained from thermodynamic viewpoint. The temperature-dependent FTIR analysis revealed that increasing temperature led to the weakening of overall H-bonding interactions and the increase of free C O and C–O–C groups. The Flory-Huggins interaction parameter χ of PAA and PPO blocks was positive and increased with increasing temperature as determined from the SAXS profiles of disordered block copolymer. The thermodynamic calculation indicated that the increase of ΔH was larger than the decrease of –TΔS with increasing temperature because of the relatively large value of χ, leading to the increase of overall ΔGmix and hence the enhanced phase separation at higher temperature.

A highly selective and sensitive optical sensor was developed to colorimetric detect trace Fe3+ ions in aqueous solution. The sensor was the sulfasalazine (SSZ) functionalized microgels (SSZ-MGs), which were fabricated via in-situ quaternization reaction. The obtained SSZ-MGs had hydrodynamic radius of about 259 &plusmn, 24 nm with uniform size distribution at 25 &deg, C. The SSZ-MG aqueous suspensions can selectively and sensitively response to Fe3+ ions in aqueous solution at 25 &deg, C and pH of 5.6, which can be quantified by UV-visible spectroscopy and also easily distinguished by the naked eye. Job&rsquo, s plot indicated that the molar binding ratio of SSZ moiety in SSZ-MGs to Fe3+ was close to 1:1 with an apparent association constant of 1.72 &times, 104 M&minus, 1. A linear range of 0&ndash, 12 &mu, M with the detection limit of 0.110 &mu, M (0.006 mg/L) was found. The obtained detection limit was much lower than the maximum allowance level of Fe3+ ions in drinking water (0.3 mg/L) regulated by the Environmental Protection Agency (EPA) of the United States. The existence of 19 other species of metal ions, namely, Ag+, Li+, Na+, K+, Ca2+, Ba2+, Cu2+, Ni2+, Mn2+, Pb2+, Zn2+, Cd2+, Co2+, Cr3+, Yb3+, La3+, Gd3+, Ce3+, and Bi3+, did not interfere with the detection of Fe3+ ions.