A Shape‐Memory DNA‐Based Hydrogel Exhibiting Two Internal Memories

The synthesis of a shape‐memory acrylamide–DNA hydrogel that includes two internal memories is introduced. The hydrogel is stabilized, at pH 7.0, by two different pH‐responsive oligonucleotide crosslinking units. At pH 10.0, one of the T‐A?T triplex DNA bridging units is dissociated, resulting in the dissociation of the hydrogel into a shapeless quasi‐liquid state that includes the other oligonucleotide bridges as internal memory. Similarly, at pH 5.0, the second type of bridges is separated, through the formation of C‐G?C⁺ triplex units to yield the shapeless quasi‐liquid state that includes the other oligonucleotide bridges as internal memory. By reversible pH triggering of the hydrogel between the values 10.0?7.0?5.0, the two internal memories cycle the material across shaped hydrogel and shapeless quasi‐liquid states. The two memories enable the pH‐dictated formation of two different hydrogel structures.     

Application of sensitive hydrogels in chemical and pH sensors

In the present work, pH-sensitive poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) blends as well as hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm), which are sensitive to organic solvent concentration in aqueous solutions, were used in silicon micromachined sensors. A sensitivity of approximately 15 mV/pH was obtained for a pH sensor with a 50 μm thick PVA/PAA hydrogel layer in a pH range above the acid exponent of acrylic acid (pK_a=4.7). The output voltage versus pH-value characteristics and the long-term signal stability of hydrogel-based sensors were investigated and the measurement conditions necessary for high signal reproducibility were determined. The influence of the preparation conditions of the hydrogel films on the sensitivity and response time of the chemical and pH sensors is discussed.     

Preparation of dual responsive low-molecular-weight hydrogel for long-lasting drug delivery

A novel low-molecular-weight hydrogel (LMWG) was fabricated by oligopeptide and phenylboronic acid to obtain a smart molecular hydrogel with dual glucose and pH response for long-term drug delivery in this study. Dual glucose and pH responsiveness of the blank molecular hydrogel was first evaluated by on-line tracking the dynamics curves using UV spectroscopy. Model drugs of phenformin for antidiabetes and doxorubicin for anticancer were selected to evaluate the drug carry and glucose/pH responsive drug release of the molecular hydrogel. The results showed the drug-loaded LMWG had good sustaining and long-lasting drug delivery in physiological or pathological environment.     

pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogels via aza‐michael addition for anticancer drug delivery

A pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogel containing “acetals” as pH‐sensitive groups and “disulfides” as reducible linkages was designed and synthesized via aza‐Michael addition reaction between PAMAM and PEGDA diacrylates. The pore size and swelling ratio of hydrogels was varied from 14 ± 3 to 19 ± 4 μm and 214 ± 13 to 300 ± 19 μm, respectively, with varying ethylene glycol repeating units in diacrylates. The swelling ratio of PEGDA/PAMAM network hydrogel increased with increase in the molecular weight of PEG and with decrease in pH. The presence of different cationizable amino‐functionalities in PEGDA/PAMAM network hydrogel helped to enhance the swelling ability of hydrogel under the acidic conditions. The continuous increase in metabolically active live HeLa cells with time in MTT assay implied biocompatibility/noncytotoxicity of the synthesized PEGDA/PAMAM injectable network hydrogel. Furthermore, the prepared PEGDA/PAMAM hydrogel showed higher degradation at lower pH and at higher concentration of DTT. The burst release of doxorubicin from PEGDA/PAMAM hydrogel under the environment of the lower pH and in presence of DTT compared to the release at normal physiological pH and in absence of DTT suggested the potential ability of this model hydrogel system for targeted and selective anticancer drug release at tumor tissues. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2080–2095     

An “Ingredients” Approach to Functional Self‐Synthesizing Materials: A Metal‐Ion‐Selective,Multi‐Responsive,Self‐Assembled Hydrogel

New methodology for making novel materials is highly desirable. Here, an “ingredients” approach to functional self‐assembled hydrogels was developed. By designing a building block to contain the right ingredients, a multi‐responsive, self‐assembled hydrogel was obtained through a process of template‐induced self‐synthesis in a dynamic combinatorial library. The system can be switched between gel and solution by light, redox reactions, pH, temperature, mechanical energy and sequestration or addition of Mg^II salt.     

Stiff,Multistimuli‐Responsive Supramolecular Hydrogels as Unique Molds for 2D/3D Microarchitectures of Live Cells

Supramolecular hydrogels constructed through molecular self‐assembly of small molecules have unique stimuli‐responsive properties; however, they are mechanically weak in general, relative to conventional polymer gels. Very recently, we developed a zwitterionic amino acid tethered amphiphilic molecule 1 , which gave rise to a remarkably stiff hydrogel comparable with polymer‐based agarose gel, retaining reversible thermal‐responsive properties. In this study, we describe that rational accumulation of multiple and orthogonal noncovalent interactions in the supramolecular nanofibers of 1 played crucial roles not only in the mechanical reinforcement but also in the multistimuli responsiveness. That is, the zwitterionic amino acid moiety and the C C double bond unit of the hydrogelator 1 can function as a pH‐responsive unit and a light‐responsive unit, respectively. We also demonstrated that this stiff and multistimuli‐responsive supramolecular hydrogel 1 is applied as a unique mold for 2D and 3D‐patterning of various substances. More significantly, we succeeded in the fabrication of a collagen gel for spatial patterning, culturing, and differentiation of live cells by using hydrogel 1 molds equipped with 2D/3D microspace channels (100–200 μm in diameter).     

Multistimuli‐Responsive,Moldable Supramolecular Hydrogels Cross‐Linked by Ultrafast Complexation of Metal Ions and Biopolymers

A new type of multistimuli‐responsive hydrogels cross‐linked by metal ions and biopolymers is reported. By mixing the biopolymer chitosan (CS) with a variety of metal ions at the appropriate pH values, we obtained a series of transparent and stable hydrogels within a few seconds through supramolecular complexation. In particular, the CS–Ag hydrogel was chosen as the model and the gelation mechanism was revealed by various measurements. It was found that the facile association of Ag⁺ ions with amino and hydroxy groups in CS chains promoted rapid gel‐network formation. Interestingly, the CS–Ag hydrogel exhibits sharp phase transitions in response to multiple external stimuli, including pH value, chemical redox reactions, cations, anions, and neutral species. Furthermore, this soft matter showed a remarkable moldability to form shape‐persistent, free‐standing objects by a fast in situ gelation procedure.     

Inorganic–organic hybrid alginate beads with LCST near human body temperature for sustained dual‐sensitive drug delivery

In order to obtain dual‐stimuli‐responsive (temperature/pH) alginate beads that exhibit LCST close to human body temperature for sustained drug release applications, poly (NIPAAm‐co‐AAm) hydrogel (with LCST 37.5°C) were selected and associated with calcium alginate to prepare inorganic–organic hybrid biomineralized polysaccharide alginate beads via a one‐step method in this paper. Scanning electron microscopy (SEM) and energy dispersive X‐ray spectrometer (EDS) results demonstrated that calcium phosphate could not only be found in the surface but also in the cross‐section of biomineralized polysaccharide beads. Both equilibrium swelling and indomethacin release behavior were found to be pH‐ and thermo‐responsive. In addition, indomethacin release profile could be sustained with a inorganic–organic hybrid membrane: the release amount reached 96% within 4 hr for the unmineralized beads, while a drug release of only 64% obtained after subjecting the biomineralized polysaccharide beads to the same treatment. These results indicate that the biomineralized polysaccharide membrane could prevent the permeability of the encapsulated drug and reduce the drug release rate effectively. The studied system has the potential to be used as an effective smart sustainable delivery system for biomedical applications. Copyright © 2008 John Wiley & Sons, Ltd.     

Multistimuli‐Responsive,Moldable Supramolecular Hydrogels Cross‐Linked by Ultrafast Complexation of Metal Ions and Biopolymers

A new type of multistimuli‐responsive hydrogels cross‐linked by metal ions and biopolymers is reported. By mixing the biopolymer chitosan (CS) with a variety of metal ions at the appropriate pH values, we obtained a series of transparent and stable hydrogels within a few seconds through supramolecular complexation. In particular, the CS–Ag hydrogel was chosen as the model and the gelation mechanism was revealed by various measurements. It was found that the facile association of Ag⁺ ions with amino and hydroxy groups in CS chains promoted rapid gel‐network formation. Interestingly, the CS–Ag hydrogel exhibits sharp phase transitions in response to multiple external stimuli, including pH value, chemical redox reactions, cations, anions, and neutral species. Furthermore, this soft matter showed a remarkable moldability to form shape‐persistent, free‐standing objects by a fast in situ gelation procedure.     

Novel Hydrogels for Rhythmic Pulsatile Drug Delivery

Summary: We are investigating an autonomous glucose-driven hydrogel/enzyme-based device prototype for rhythmic, pulsed delivery of gonadotropin releasing hormone (GnRH). The device employs a pH-sensitive hydrogel membrane in conjunction with the enzyme glucose oxidase. This system delivers GnRH in rhythmic pulses when exposed to a constant level of glucose. These pulses result from autonomous pH oscillations inside the device that are created by an unstable nonlinear feedback between hydrogel permeability to glucose and production of acid by glucose oxidase. Previous versions of this prototype utilized p(N-isopropylacrylamide-co-methylacrylic acid) p(NIPA-co-MAA) hydrogels, with 10 mol% MAA incorporated. With this membrane, which undergoes a volume transition (VT) near pH 5, pH oscillations centered around pH 5 are observed. This range is too low to sustain oscillations in physiologically buffered media. To shift the operating pH of oscillations closer to physiologic pH, we have sought ways to increase the pH of the volume transition. In this study we show that increasing the side chain length of the α-alkylacrylic acid (RAA) comonomer enhances the overall hydrophobicity of the copolymer, and shifts the VT pH closer to physiological pH values. We also demonstrate the ability of such membranes to affect an alkaline shift in the range of oscillations in the prototype oscillator device.     

DNA-SWNT hybrid hydrogel

In this communication, we report the preparation of DNA-SWNT hybrid hydrogel which is pH responsive and strength tunable.     

Synthesis of poly(ethylene glycol)‐based hydrogels and their swelling/shrinking response to molecular recognition

To synthesize the novel molecular‐ and pH‐stimulus‐responsive hydrogel, we prepared poly(ethylene glycol)‐based hydrogel containing ionic groups. We evaluated the fundamental swelling/shrinking properties of the hydrogels synthesized by various conditions. Decreasing the molecular weight of a crosslinker provided the increasing of the equilibrium swelling ratio. Also, the equilibrium swelling ratio was changed by the introduction of functional ionic monomers and its compositions. Furthermore, the swelling/shrinking behaviors of the hydrogels were affected by the environmental condition of aqueous solution, in fact the hydrogels were considerably shrunk (to one‐fifth volume) using a di‐ionic solute in the aqueous solution through the ionic interactions between the hydrogel and the solutes. Additionally, the specific shrinking to diamine compounds was also observed in response to pH change. These results clearly show the swelling/shrinking responsibility of the hydrogels toward the molecular recognitions and its pH conditions. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3153–3158     

氧化石墨烯/聚合物复合水凝胶的研究进展

氧化石墨烯是一种具有单原子厚度的二维材料, 具有优异的力学性能和良好的水分散性, 其表面有大量的含氧官能团. 将氧化石墨烯引入水凝胶体系中可以提高水凝胶的机械性能, 丰富其刺激响应的类型. 目前, 氧化石墨烯水凝胶在高强度、 吸附、 自愈合及智能材料等很多领域均有出色的表现. 氧化石墨烯水凝胶的研究已有10年的历史. 本文总结了氧化石墨烯水凝胶的制备方法, 归纳了智能氧化石墨烯水凝胶在光热响应、 pH响应和自愈合3个方面的响应机理和研究进展, 并综合评述了其在高强度水凝胶、 生物医学、 智能材料和污水处理等方面的应用前景.     

Preparation of a novel pH-responsive silver nanoparticle/poly(HEMA-PEGMA-MAA) composite hydrogel

In this paper, series of novel pH-responsive silver (Ag) nanoparticle/poly(2-hydroxyethyl methacrylate (HEMA)-poly(ethylene glycol) methyl ether methacrylate (PEGMA)-methacrylic acid (MAA)) composite hydrogel were successfully prepared by in situ reducing Ag⁺ ions anchored in the hydrogel by the deprotonized carboxyl acid groups. X-ray diffraction (XRD), UV-vis spectrophotometry, transmission electron microscopy (TEM) and electric conductivity tests were used to characterize the composite system. It was found that the size and morphology of the reduced Ag nanoparticles in the composite hydrogels could be changed by loading the Ag⁺ ions at various swelling ratios of hydrogel. Moreover, compared to the pure poly(HEMA-PEGMA-MAA) hydrogel, not only did the Ag nanoparticle/poly(HEMA-PEGMA-MAA) composite hydrogels exhibit much higher swelling ratio and faster deswelling rate, but also higher pH switchable electrical properties upon controlling the interparticle distance under pH stimulus. The pH responsive nanocomposite hydrogel reported here might be a potentially smart material in the range of applications including electronics, biosensors and drug-delivery devices.     

石墨烯/有机共轭体系的光热效应与应用

本文对近几年来石墨烯/有机共轭体系在光热效应领域取得的重要研究进展进行了总结评述。虽然有机光热试剂具有优异的光热转换效率和良好的生物相容性,但是,有机光热试剂的光稳定性差,限制了其实际应用。现有研究结果表明,石墨烯可显著地增强有机共轭体系的光稳定性,大幅提高其光热转换效率。此外,石墨烯/有机共轭体系还可集多种功能于一体,例如:光声成像指导下的光热治疗、pH响应的荧光成像和光热治疗、光热和光动力联合治疗等,这对有机共轭体系在光热治疗领域的应用具有重要意义。本文总结的研究结果及所作的分析,希望对新型有机共轭体系的光热效应及后续研究起到一定的参考和促进作用。     

Water-in-oil emulsion separation within a milli-fluidic device

A milli-fluidic method capable of continuous passive separation of water-in-oil emulsions with an efficiency of ～90% is described. Experiments used high oleic sunflower oil or mineral oil as the continuous phase and aqueous solutions of methylene blue, crystal violet, or dextran with methylene blue as the dispersed phase. To achieve continuous passive separation, a device with opposing channel walls of disparate hydrophobicity is used to stabilize cocurrent laminar flow of oil and water. The disparity in hydrophobicity of the channel walls is accomplished by defining one length of the channel with a hydrogel, in this case polyethylene glycol. Emulsion separation is facilitated by introducing the emulsion at the water/hydrogel interface. Advantages of performing separations at the milli-fluidic scale are presented.     

Electroaddressing agarose using Fmoc-phenylalanine as a temporary scaffold

Electroaddressing, the use of imposed electrical stimuli to guide assembly, is attractive because electrical stimuli can be conveniently applied with high spatial and temporal resolution. Several electroaddressing mechanisms have been reported in which electrode-induced pH gradients trigger stimuli-responsive materials to undergo localized sol-gel transitions to form hydrogel matrices. A common feature of existing hydrogel electrodeposition mechanisms is that the deposited matrix retains residual charged, acidic, or basic (macro)molecules. Here, we report that pH-responsive fluorenyl-9-methoxycarbonyl-phenylalanine (Fmoc-Phe) can be used to codeposit the neutral and thermally responsive polysaccharide agarose. Upon cooling, an agarose network is generated and Fmoc-Phe can be removed. The Fmoc-Phe-mediated codeposition of agarose is simple, rapid, spatially selective, and allows for the electroaddressing of a bioactive matrix.     

Drug release of pH/temperature-responsive calcium alginate/poly(N-isopropylacrylamide) semi-IPN beads

A series of semi-interpenetrating, polymer network (semi-IPN), hydrogel beads, composed of calcium alginate (Ca-alginate) and poly(N-isopropylacrylamide) (PNIPAAM), were prepared for a pH/temperature-sensitive drug delivery study. The equilibrium swelling showed the independent pH- and thermo- responsive nature of the developed materials. At pH=2.1, the release amount of indomethacin incorporated into these beads was about 10% within 400 min, while this value approached to 95% at pH=7.4. The release rate of the drug was higher at 37 degrees C than that at 25 degrees C and increased slightly with increasing PNIPAAM content. These results suggest that the Ca-alginate/PNIPAAM beads have the potential to be used as an effective pH/temperature sustainable delivery system of bioactive agents. [GRAPHS: SEE TEXT] A summary of the temperature- and pH-dependence on the release of the drug over a period of 450 min. The effect of the temperature on the swelling of the beads is shown in the inset.     

Orthogonal Dual‐Triggered Shape‐Memory DNA‐Based Hydrogels

DNA‐based shape‐memory hydrogels revealing switchable shape recovery in the presence of two orthogonal triggers are described. In one system, a shaped DNA/acrylamide hydrogel is stabilized by duplex nucleic acids and pH‐responsive cytosine‐rich, i‐motif, bridges. Separation of the i‐motif bridges at pH 7.4 transforms the hydrogel into a quasi‐liquid, shapeless state, that includes the duplex bridges as permanent shape‐memory elements. Subjecting the quasi‐liquid state to pH 5.0 or Ag⁺ ions recovers the hydrogel shape, due to the stabilization of the hydrogel by i‐motif or C‐Ag⁺‐C bridged i‐motif. The cysteamine‐induced transformation of the duplex/C‐Ag⁺‐C bridged i‐motif hydrogel into a quasi‐liquid shapeless state results in the recovery of the shaped hydrogel in the presence of H⁺ or Ag⁺ ions as triggers. In a second system, a shaped DNA/acrylamide hydrogel is generated by DNA duplexes and bridging Pb²⁺ or Sr²⁺ ions‐stabilized G‐quadruplex subunits. Subjecting the shaped hydrogel to the DOTA or KP ligands eliminates the Pb²⁺ or Sr²⁺ ions from the respective hydrogels, leading to shapeless, memory‐containing, quasi‐liquid states that restore the original shapes with Pb²⁺ or Sr²⁺ ions.     

Preparation and characterization of a novel IPN hydrogel memberane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAM/CMCS)

A novel type of interpenetrating polymer networks (IPN) hydrogel membrane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAm)/(CMCS) was prepared, and the effects of the feed ratio of components, swelling medium and irradiation dose on the swelling and deswelling properties of the hydrogel was systematically studied. The results showed that the introduction of CMCS did not shift the LCST (at 32 °C), which is similar to the pure PNIPAAm. The lowest swelling ratio was at pH 2. There was little influence of irradiation dose on the thermo- and pH-sensitivity of the IPN hydrogel, increasing dose only decreased the swelling ratio. The PNIPAAm:CMCS=1:4 w/w hydrogel was not thermo-sensitive in distilled water, whereas it showed a discontinuous volume phase transition in pH 2 and a continuous one in pH 8 buffer. Consequently, a combination of pH and temperature can be coupled to control the responsive behavior of these hydrogels.