Leveraging the gel-to-sol transition of physically crosslinked thermoresponsive polymer hydrogels to enable reactions induced by lowering temperature.

Much work has been done on the use of heating to trigger reactions via the temperature-dependent removal of a barrier or constraint separating reagents. Far less work, however, has been done on the use of cooling to achieve a similar goal. Numerous applications, such as those involving components or materials susceptible to persistent low temperatures and cases in which energy for heating is not available, would benefit from this inverse approach. Hence, in this study we explore whether physically crosslinked hydrogels can be reliably used as thermoresponsive constraints that allow reagents to react only upon cooling. We achieve this by loading reagents into adjacent blocks of thermoresponsive hydrogel and showing that these reagents can only react with each other after the temperature of the hydrogel falls below its lower critical solution temperature (LCST). Above the LCST, the reagents remain sequestered in separate gels and no reaction occurs; this "OFF" state is stable for extended periods. When the system is allowed to cool, the hydrogels liquify and flow into each other, allowing mixing of the embedded reagents ("ON" state). We tune the hydrogels' LCSTs using NaCl, quantify the NaCl's tuning effect using rheometry, and determine that reactions are triggered reproducibly at temperatures similar to the tuned LCSTs. We also demonstrate generalizability of the concept by exploring situations involving radically different reaction types. This concept therefore constitutes a new approach to autonomous material behavior based on cooling.

Pt Nanoparticles Supported on a Dynamic Boronate Ester-Based G-quadruplex Hydrogel as a Nanoreactor.

Herein, we have reported a dynamic boronic ester mediated guanosine (G) based G-quadruplex hydrogel as an ideal template for in situ and 'green chemical' approach for the synthesis and stabilization of Pt NPs. 11 B NMR and FT-IR spectra reveal the formation of dynamic boronate ester bonds. The TEM images of the G-quadruplex hydrogel reveal entangled three-dimensional (3D) crosslink nanofibrillar networks with average diameter of 20 nm. Similarly, AFM images of the hydrogel show dense nanofibrillar assembly with an average height of 6 nm. The in situ generated Pt NPs have been characterized using TEM and XPS techniques. The average size of the nanofiber supported Pt NPs is 1.5 nm. The Pt NPs embedded G-quadruplex hydrogel shows better mechanical stiffness than the native hydrogel as the storage modulus (G') increases to 2250 Pa from 317.08 Pa after the in situ generation of Pt NPs. Furthermore, G-quadruplex hydrogel supported Pt NPs have been used as a catalytic system for hydrogenation reaction of different aromatic nitro compounds in aqueous medium. The use of G-quadruplex molecular system as a template for the synthesis and stabilization of metal NPs would be an interesting area of research.

Engineered Dynamic Boronate Ester-Mediated Self-Healable Biocompatible G-Quadruplex Hydrogels for Sustained Release of Vitamins.

Injectable, self-healable, and biocompatible dynamic hydrogels prepared from the molecular self-assembly and reversible covalent bond formation of low-molecular-weight hydrogelators are increasing in the field of drug delivery. Herein, we report the formation of G-quadruplex hydrogels via the multicomponent self-assembly and reversible bond formation between guanosine (G) and 1-naphthaleneboronic acid in the presence of the monovalent cation K+. The cation-templated stacking interaction of G4 quartets and the formation of dynamic cyclic boronate esters are responsible for the construction of dynamic G-quadruplex assembly. The in situ-synthesized dynamic cyclic boronate esters are well characterized by 11B nuclear magnetic resonance and Fourier transform infrared spectroscopy methods. The formation and morphology of the G-quadruplex hydrogel are well supported by several spectroscopic and microscopic techniques. The injectability and self-healing ability of the G-quadruplex hydrogel are also investigated. The in vivo cytotoxicity of the G-quadruplex hydrogel is extensively evaluated over different cell lines (HeLa, MCF-7, and HEK293) to observe the biostability and broad-spectrum biocompatibility of the hydrogel. Further, this injectable, biocompatible G-quadruplex hydrogel has been used for encapsulation and sustained release of two important vitamins (B2 and B12) over 40 h at physiological pH (7.46) and temperature (37 °C) without the influence of any external stimuli.

PEG Functionalized Stimuli Responsive Self-Healable Injectable Dynamic Imino-boronate G-quadruplex Hydrogel for the Delivery of Doxorubicin.

Dynamic G-quadruplex hydrogel is engineered by using guanosine, 2-formylphenylboronic acid, and 4-Arm PEG-NH2. The gelation conditions are optimized by varying concentrations of the gelators, pH, and different alkali metal ions. The formation of imino-boronate bonds during the gelation process is fully characterized with FT-IR, 1H NMR, and 11B NMR spectroscopy. The secondary supramolecular G-quadruplex structure and the formation of nanofibrillar morphology are well examined using several spectroscopic and microscopic techniques. The mechanical strength of the hydrogel is investigated by rheological experiments. The hydrogel is injectable and self-healable due to the dynamic nature of the imono-boronate bonds. The dynamic bonds provide distinct shear-thinning and thixotropic properties to the resulting hydrogel with almost 90% recovery of its mechanical strength after four cycles. The pH responsive behavior of the hydrogel is achieved by pH sensitive imino-boronate bonds, which are unstable at acidic pH. To investigate the biocompatibility of the hydrogel, a wide range of hydrogel concentrations are examined by in vitro cell culture experiments using the MCF-7 cell line. After a biocompatibility test of the hydrogel, the anticancer drug doxorubicin is incorporated inside the gel to analyze the drug release profile at different pHs. The release rate of the loaded drug is observed faster in lower pH (pH 4.8) than in physiological pH (pH 7.4). Different release rate of the drug from the drug loaded hydrogel in different pHs is driven by the pH sensitive imino-boronate bonds. The release profile of the drug is slow, sustain and steady.

Alpha Neurofeedback Has a Positive Effect for Participants Who Are Unable to Sustain Their Alpha Activity.

Alpha rhythm (8-13 Hz) is linked to relaxed mental state in humans. Earlier reports have shown that individuals can increase their alpha power if provided with a valid feedback, compared to controls who are provided invalid feedback. However, these results remain controversial, partly because controls may be in a different behavioral state, making it difficult to directly compare their alpha power with the valid group. We here address this issue by using an experimental paradigm in which an invalid feedback is given on a fraction of trials, such that both valid and invalid conditions can be obtained from the same participant. Using electroencephalography (EEG), we recorded alpha power from the occipital area from 24 humans (nine females) and played a feedback tone which could be valid (tone frequency proportional to alpha power), invalid (tone sequence from a previous valid trial; participants were unaware of this condition), or neutral (constant tone frequency). We found that during eyes closed-state, neurofeedback did not enhance alpha activity beyond pre-trained state within the experimental duration, probably because of saturation of alpha rhythmicity. However, for participants whose alpha power decreased over time within a trial, valid feedback helped them to sustain alpha more than invalid feedback. Further, alpha increase showed a weak negative correlation with their self-reported attentional load but was uncorrelated with relaxation levels. Our results reconcile many conflicting reports in the neurofeedback literature, and show that even under most stringent control, valid neurofeedback can help participants who are otherwise unable to sustain their alpha activity.

Investigations of Anti-Inflammatory Activity of a Peptide-Based Hydrogel Using Rat Air Pouch Model.

The growing area of biomaterial sciences has attracted broad attention in recent years in the development of peptide-based biocompatible materials with inherent therapeutic potentials. Here, we developed an Amoc (9-anthracenemethoxycarbonyl)-capped dipeptide-based biocompatible, injectable, thixotropic, and self-healable hydrogel. In vitro cytotoxicity of the hydrogel was investigated with the human embryonic kidney cell (HEK293) line. We observed that the synthesized peptide is noncytotoxic. The hydrogel showed an antibacterial efficacy against Gram-positive and Gram-negative bacteria. In vivo anti-inflammatory activity of the hydrogel was investigated using the rat air pouch model of acute inflammation. The major parameters considered for the anti-inflammatory study were exudate volume, total and differential white blood cell count, tissue histology, and lipid peroxidation assay. These experimental data suggest biocompatibility and potential therapeutic applications of peptide hydrogel in inflammation.

Redox-Active Dynamic Self-Supporting Thixotropic 3D-Printable G-Quadruplex Hydrogels.

Redox-active G-quadruplex hydrogels were prepared by dynamic boronate ester formation between ferroceneboronic acid and guanosine. Dynamic boronate esters imparted thixotropic and 3D-printability to the hydrogel. Initially, the ferrocene moiety was oxidised to produce a weaker ferrocenium-based green hydrogel. However, the less stable ferrocenium converted into more stable ferrocene to produce a hydrophobic, water-stable and robust hydrogel.

Arylboronate esters mediated self-healable and biocompatible dynamic G-quadruplex hydrogels as promising 3D-bioinks.

Extrudable G-quadruplex hydrogels were prepared at physiological pH. Gels with suitable mechanical properties were explored as 3D-bioinks. The 3D printing process is driven by injectability and the highly thixotropic and self-healable nature of the gel. High cell viability and homogeneous cell distribution within the gel make it a promising material as a 3D bioink.