Stimuli-responsive Polymer Hydrogels Research Articles

Recent Developments and Future Challenges of Hydrogels as Draw Solutes in Forward Osmosis Process

Forward osmosis (FO) has been recently regarded as a promising water treatment technology due to its lower energy consumption and lower membrane fouling propensity compared to the reverse osmosis (RO). The absence of suitable draw solute constraints the wide-range application of the FO. Hydrogels are three-dimensional hydrophilic polymer networks that can absorb a huge amount of water. Particularly, stimuli-responsive polymer hydrogels can undergo a reversible volume change or solution-gel phase transition in response to external environmental stimuli, including temperature, light, pressure, solvent composition, and pH. These intrinsic properties indicate the lowest regeneration cost of draw solutes compared to the thermal method and other membrane processes. This review aims to introduce the research progress on hydrogels as draw solutes, clarify the existing problems and point out the further research direction.

Functional Stimuli-Responsive Gels: Hydrogels and Microgels.

One strategy that has gained much attention in the last decades is the understanding and further mimicking of structures and behaviours found in nature, as inspiration to develop materials with additional functionalities. This review presents recent advances in stimuli-responsive gels with emphasis on functional hydrogels and microgels. The first part of the review highlights the high impact of stimuli-responsive hydrogels in materials science. From macro to micro scale, the review also collects the most recent studies on the preparation of hybrid polymeric microgels composed of a nanoparticle (able to respond to external stimuli), encapsulated or grown into a stimuli-responsive matrix (microgel). This combination gave rise to interesting multi-responsive functional microgels and paved a new path for the preparation of multi-stimuli “smart” systems. Finally, special attention is focused on a new generation of functional stimuli-responsive polymer hydrogels able to self-shape (shape-memory) and/or self-repair. This last functionality could be considered as the closing loop for smart polymeric gels.

Modeling drug release through stimuli responsive polymer hydrogels

There is a rising interest in stimuli-responsive hydrogels to achieve controlled and self-regulated drug delivery. Stimuli responsive polymer hydrogels with their ability to swell/de-swell under varying pH conditions present themselves as a potential candidate for controlled drug delivery. It is important to develop a mechanistic understanding of the underlying phenomena that will help suggest ways to control the drug release from a polymer hydrogel. We present a mathematical model that couples Nernst–Planck, Poisson and force balance equations to incorporate diffusion of ionic species and drug along with deformation of hydrogel under osmotic pressure. The model can be used to simulate swelling behaviour of the hydrogel along with the kinetics of drug release. It has been validated with published experimental data for swelling of polyhydroxyethyl methacrylate-co-methacrylic acid (pHEMA-co-MA) gels and release kinetics of Phenylpropanolamine from these gels. Effect of formulation parameters such as polymer concentration and cross-linker concentration has also been evaluated. The model can be used to reduce the number of exploratory experiments required during design of a drug delivery system.

Design Strategies of Stimuli-Responsive Supramolecular Hydrogels Relying on Structural Analyses and Cell-Mimicking Approaches.

Stimuli-responsive hydrogels are intriguing biomaterials useful for spatiotemporal controlled release of drugs, cells, and biological cues, cell engineering for various applications, and medical diagnosis. To date, many physical and chemical stimuli-responsive polymer hydrogels have been developed by chemical modification of polymer chains and cross-linking points. In particular, conjugation with biomolecules to polymers produced promising biomolecule-responsive hydrogels. These examples clearly indicate high potentials of stimuli-responsive hydrogels as promising biomaterials. In addition to polymer hydrogels, supramolecular hydrogels formed by the assembly of small molecules (hydrogelators) via noncovalent interactions have also been regarded as unique and promising soft materials due to their flexible programmability in rendering them stimuli-responsive with the larger macroscopic change (i.e., gel-sol transition). This Account describes our strategies for the rational design of stimuli-responsive supramolecular hydrogels and their biological applications. Following the detailed structural analysis of a lead hydrogelator that clearly indicates the appropriate sites for incorporation of stimuli-responsive modules, we designed supramolecular hydrogels capable of responding to simple physical (thermal and light) and chemical (pH and metal ions) stimuli. More importantly, biomolecule-responsive hydrogels were successfully developed by supramolecularly mimicking the complex yet well-ordered structures and functions of live cells containing multiple components (a cell-mimicking approach). Development of biomolecule-responsive supramolecular hydrogels has been difficult as the conventional strategy relies on the chemical incorporation of stimuli-responsive modules, owing to the lack of modules that can effectively respond to structurally diverse and complicated biomolecules. Inspired by natural systems where functional compartments (e.g., cell organelles) sophisticatedly interact with each other, we sought to integrate the two distinct microenvironments of supramolecular hydrogels (the aqueous cavity surrounded by fibers and the fluidic hydrophobic fiber domain) with other functional materials (e.g., enzymes, peptides or proteins, fluorescent chemosensors, or inorganic porous or layered nanomaterials) for biomolecule responses. In situ fluorescence microscopy imaging clearly demonstrated that chemical isolation and crosstalk are highly successful between the integrated microenvironments in supramolecular hydrogels, similar to organelles in living cells, which allow for the construction of unique optical response and sensing systems for biomolecules. Furthermore, programmed hybridization of our chemically reactive hydrogels with appropriate enzymes can provide an unprecedented universal platform for biomolecule-degradable supramolecular hydrogels. Such biomolecule-responsive hydrogels are a potentially promising tool for user-friendly early diagnostics and on-demand drug-releasing soft materials. We expect that our rational design strategies for stimuli-responsive supramolecular hydrogels by modification of chemical structures and hybridization with functional materials will inspire scientists in various fields and lead to development of novel soft materials for biological applications.

A Multiresponsive Anisotropic Hydrogel with Macroscopic 3D Complex Deformations

As one of the most promising smart materials, stimuli‐responsive polymer hydrogels (SPHs) can reversibly change volume or shape in response to external stimuli. They thus have shown promising applications in many fields. While considerable progress of 2D deformation of SPHs has been achieved, the realization of 3D or even more complex deformation still remains a significant challenge. Here, a general strategy towards designing multiresponsive, macroscopically anisotropic SPHs (MA‐SPHs) with the ability of 3D complex deformations is reported. Through a local UV‐reduction of graphene oxide sheets (GOs) with a patterned fashion in the GO‐poly(N‐isopropylacrylamide) (GO‐PNIPAM) composite hydrogel sheet, MA‐SPHs can be achieved after the introduction of a second poly(methylacrylic acid) network in the unreduced part of GO‐PNIPAM hydrogel sheet. The resulting 3D MA‐SPHs can provide remote‐controllable light‐driven, as well as thermo‐, pH‐, and ionic strength‐triggered multiresponsive 3D complex deformations. Approaches in this study may provide new insights in designing and fabricating intelligent soft materials for bioinspired applications.

Microfiber-polymer hydrogel monolith as forward osmosis draw agent

Stimuli-responsive polymer hydrogels have shown great potential for use as draw agent in emerging forward osmosis (FO) technology. The swelling pressure of hydrogel and the effective contact area between FO membrane and hydrogel are key parameters for achieving high water flux. In this work, we have demonstrated that the forward osmosis performance of hydrogels can be significantly improved by producing composite hydrogel monoliths containing thermoplastic polyurethane (TPU) microfibers. The use of monolithic hydrogels and the addition of microfibers enhance water diffusion through the draw agent and sustain high swelling pressure, resulting in improved FO performance. As observed in the sigmoidal swelling curves, the swelling kinetics of microfiber–hydrogel composite (TPU microfiber-poly (NIPAM-co-SA), TPU-PN5S5) is faster than that of pure hydrogel (PN5S5), and the time required for the composite to reach swelling equilibrium decreases significantly; the diffusion exponent of TPU-PN5S5 composite increases from 0.73 to 0.81, indicating that addition of microfibers increases the water diffusion rate. Further studies show that water transports more quickly through the microchannels around TPU microfibers due to their hydrophilicity and capillary forces. The composite monolith was tested as forward osmosis draw agent, and it was found that the 1st hour FO water flux and dewatering flux of TPU-PSA are 1.81 and 3.51 L m−2 h−1, respectively, twice of those for PSA particles alone.

Hybrid cross-linked hydrogels based on fibrous protein/block copolymers and layered silicate nanoparticles: tunable thermosensitivity, biodegradability and mechanical durability

Schematic representation of LAPONITE® reinforced pluronic/chitosan/keratin nanocomposite hydrogel crosslinked with Genipin.

PH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells

Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.

Smart draw agents for emerging forward osmosis application

Forward osmosis (FO) membrane technology has attracted rapidly growing research interest because it shows great potential in reducing energy consumption and costs in water desalination and treatment. The lack of a suitable draw agent has been identified as a challenging problem in the commercial implementation of FO technology. Recent years have seen significant advances in the development of smart draw agents with responsive properties, from which water can be recovered under different stimuli. This review highlights the properties and performance of some interesting smart draw agents reported recently, including functionalized magnetic nanoparticles, thermo-responsive polyelectrolytes, and stimuli-responsive polymer hydrogels.

Effect of particle size on the performance of forward osmosis desalination by stimuli-responsive polymer hydrogels as a draw agent

Stimuli-responsive polymer hydrogels have shown great potential for use as a draw agent in forward osmosis desalination. We have previously shown that the alteration of chemical structure of hydrogel network via the incorporation of ionic groups and light-absorbing particles can significantly improve the efficiency of hydrogels used as draw agent in FO desalination. In this study, particle size is demonstrated to be another key parameter in determining the efficacy of these materials as the draw media. Hydrogel copolymers of sodium acrylate and N-isopropylacrylamide of different particle sizes were prepared via free-radical polymerization and tested as draw agents. The results showed that the initial swelling rate of small particles (2–25μm) was much higher than that of large particles (e.g., 500–1000μm), with the diffusion mechanism shifted from non-Fickian to Fickian diffusion as the particle size decreases. To reclaim the fresh water drawn through the membrane by the polymer particles, the gas pressure and heating were applied as the stimuli on the draw agent to release water. Gas pressure was found to be an effective method of regaining the pure water, and is a more readily applicable method industrially than our previous mechanical pressing. It was found that greater liquid water recovery amounts were achieved from large hydrogel particles, whereas more water was recovered from smaller particles under such a thermal stimulus. This is likely due to the fact that hydrogel particles with different sizes showed different interstitial volumes, particle–particle contact areas, particle-membrane contact zones and hydrogel thickness on the membrane surface.

Stimuli-responsive polymer hydrogels as a new class of draw agent for forward osmosis desalination

Ionic polymer hydrogels with thermal responsive units are found to induce higher water permeation rates in the osmosis process, and higher water release rates under a combination of pressure and thermal stimuli. These hydrogels have the potential for use as draw agent in forward osmosis desalination.

Stimuli-responsive polymer hydrogels containing partially exfoliated graphite

In this work, a new stimuli-responsive composite polymer hydrogel containing partially exfoliated graphite was prepared by frontal polymerization. The materials obtained were characterized by differential scanning calorimetry, RAMAN, scan electron microscopy, transmission electron microscopy, atomic force microscopy, and in terms of swelling behavior. It was found that the maximum temperature reached by the polymerization front and the lower critical solution temperature are affected by the graphite content. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

Research Trends of Stimuli-Responsive Polymer Hydrogels in Japan

In recent years, biological functions have been increasingly investigated on the molecular and/or atomic level. Synthesis and assemblies of various functional polymers have also been researched. In particular, research of stimuli-responsive polymeric materials having the func tion and efficiency of a biological system has been of interest. The materials are still in the embryonic period, but there are great expectations surrounding their progress. In this article, the research trends in Japan of stimuli-responsive polymer gel are summarized from the viewpoint of synthesis, fabrication, and applications. On synthesis, researches have been summarized on stimuli including light, heat or temperature, pH or ion, electric field, and chemicals. On fabrication, researches have been summarized on two types of fabrication methods: chemical methods, such as grafting and hybridization; and physical methods, such as blend, microgel, film, fiber and composite. On industrial applications, many at tempts have been made in recent years concerning the released control of chemicals, especially drug delivery systems. Controls of adsorption, permeation, and enzyme reaction using stimuli-responsive polymer gels have also been attempted in the chemical engineering and bioengineering fields. On applications to actuators, the construction of some micro-actuating systems has been attempted. The stimuli-responsive polymer gels (chemomechanical gels) are very promising, both in the field of fundamental study and in the field of applied research.