Search

Smart hydrogels which can respond to external stimuli have been widely focused with increasing interest. Thereinto, magnetic-responsive hydrogels that are prepared by embedding magnetic nanomaterials into hydrogel networks are more advantageous in biomedical applications due to their rapid magnetic response, precisely temporal and spatial control and non-invasively remote actuation. Upon the application of an external magnetic field, magnetic hydrogels can be actuated to perform multiple response modes such as locomotion, deformation and thermogenesis for therapeutic purposes without the limit of tissue penetration depth. This review summarizes the latest advances of magnetic-responsive hydrogels with focus on biomedical applications. The synthetic methods of magnetic hydrogels are firstly introduced. Then, the roles of different response modes of magnetic hydrogels played in different biomedical applications are emphatically discussed in detail. In the end, the current limitations and future perspectives for magnetic hydrogels are given.

Hydrogels are significant hydrophilic materials with 3D polymeric network structures, which have received much attention in recent decades. DNA-based hydrogel materials have been widely used for ti...

The pH-sensitive hydrogels are a unique class of three-dimensional hydrophilic polymers containing ionic pendant groups on their polymeric network. In response to the external pH variation, these materials span the volume of an aqueous/biological solution and swell without dissolution. Nowadays, the pH-sensitive hydrogels have attracted the growing interest of many researchers in various fields of researches such as drug delivery, tissue engineering, soft actuators, etc. which makes the simulation of their behavior crucial for optimum utilization. The essential prerequisite for the simulation of these materials is the swelling theory. In this article, we present a review of the fundamental phenomena in swelling theories of the pH-sensitive hydrogels. We also classify the swelling theories into two groups including the monophasic and multiphasic theories. Then, we briefly examine the most highlighted swelling theories in each group. The experimental data is essential for material parameters estimation as well as verification of the constitutive equations. Thus, we introduce and discuss the most highlighted experiments on the swelling and deswelling behavior of the pH-sensitive hydrogels as well.

Understanding the surrounding atmosphere and reacting accordingly with a precise action are always fascinating features of a material. Materials that pose such responsiveness are called smart materials. Currently, research studies on smart materials are being accelerated exponentially around the world; this is also true for smart hydrogels. Smart hydrogels with various chemically and structurally responsive moieties exhibit excellent characteristics of reacting under different environmental conditions such as pH, temperature, light, electric field, and magnetic field as well as biological and chemical stimuli. These smart hydrogels are drawing the attention of researchers for a wide range of applications, for instance, in designing biomedical, industrial, agricultural, electrical, healthcare, and hygienic products. This review encompasses the latest developments in the field of smart hydrogel synthesis based on their unique features and different aspects of their responsive behaviors. Additionally, this paper covers some of the recent strategies for tuning special functional properties of smart hydrogels for targeted applications.

Smart hydrogels are of great interest in areas such as drug delivery and sensing. Dendrimer-based hydrogels can exhibit tunable properties due to their structural precision. We prepared hydrogels from self-immolative dendrons. Controlled hydrogel degradation in response to light was demonstrated and the hydrogel properties as a function of dendron generation were compared.

Stimuli-responsive smart hydrogels have garnered considerable interest for their potential in biomedical applications. While widely utilized, little is known about the rheological and mechanical properties of the hydrogels with respect to the type of cross-linker in a systematic manner. In this study, we present a facile synthetic route toward ABA triblock copolymer hydrogels based on poly(ethylene oxide) (PEO). Two classes of hydrogels were prepared by employing the functional allyl glycidyl ether (AGE) monomer during the polymerization followed by the subsequent post-polymerization modification of prepared PAGE

Here we report the synthesis and viscoelastic properties of smart hydrogels based on N-isopropylacrylamide, cationic (3-acrylamidopropyl)trimethylammonium chloride and nanoclay. Hydrogels were prepared by aqueous free radical polymerization. The effect of some salts, N,N '-methylenebisacrylamide, (3-acrylamidopropyl)trimethylammonium chloride and nanoclay content on the viscoelastic properties was studied. Also volume phase transition temperature and thermal behavior of the prepared hydrogels were investigated. Synthetic nanoclay and anionic groups of the bind to the cationic co-monomer units and significantly affected the viscoelasticity and thermal properties of the hydrogels. DSC measurements showed that the volume phase transition temperature of hydrogels depended on nanoclay content. By introducing of co-monomer, 250 mM solution of NaCl 15 mM bis(trifluoromethane)sulfonimide lithium salt (LiNTF2) and laponite nanoclay, a 10, 4, and 3.8 fold increase in elastic module was obtained, respectively, compared to that of the homopolymer PNIPAM hydrogel. With a temperature change from 20 to 45°C for the homopolymer PNIPAM hydrogel in 15 mM LiNTF2, the elastic module grew 5 times larger.

Among modern drug formulations, stimuli-responsive hydrogels also called "smart hydrogels" deserve a special attention. The basic feature of this system is the ability to change their mechanical properties, swelling ability, hydrophilicity, bioactive molecules permeability, etc., influenced by various stimuli, such as temperature, pH, electromagnetic radiation, magnetic field and biological factors. Therefore, stimuli-responsive matrices can be potentially used in tissue engineering, cell cultures and technology of innovative drug delivery systems (DDSs), releasing the active substances under the control of internal or external stimuli. Moreover, smart hydrogels can be used as injectable DDSs, due to gel-sol transition connected with in situ cross-linking process. Innovative smart hydrogel DDSs can be utilized as matrices for targeted therapy, which enhances the effectiveness of tumor chemotherapy and subsequently limits systemic toxicity. External stimulus sensitivity allows remote control over the drug release profile and gel formation. On the other hand, internal factors provide drg accumulation in tumor tissue and reduce the concentration of active drug form in healthy tissue. In this report, we summarise the basic knowledge and chemical strategies for the synthetic smart hydrogel DDSs applied in antitumor therapy.

In this paper, injectable, thermosensitive smart hydrogel local drug delivery systems (LDDSs) releasing the model antitumour drug 5-fluorouracil (5-FU) were developed. The systems were based on biodegradable triblock copolymers synthesized via ring opening polymerization (ROP) of ε-caprolactone (CL) in the presence of poly(ethylene glycol) (PEG) and zirconium(IV) acetylacetonate (Zr(acac)4), as co-initiator and catalyst, respectively. The structure, molecular weight (Mn) and molecular weight distribution (Đ) of the synthesized materials was studied in detail using nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC) techniques, the optimal synthesis conditions were determined. The structure corresponded well to the theoretical assumptions. The produced hydrogels demonstrated a sharp sol–gel transition at temperature close to physiological value, forming a stable gel with good mechanical properties at 37 °C. The kinetics and mechanism of in vitro 5-FU release were characterized by zero order, first order, Higuchi and Korsmeyer–Peppas mathematical models. The obtained results indicate good release control, the kinetics were generally defined as first order according to the predominant diffusion mechanism, and the total drug release time was approximately 12 h. The copolymers were considered to be biodegradable and non-toxic, the resulting hydrogels appear to be promising as short-term LDDSs, potentially useful in antitumor therapy.

Smart hydrogels with multistimuli responsiveness have been increasingly exploited as soft matters for biomedical applications in drug delivery, tissue engineering, and bioactuators. While many of t...

Chitosan as a natural polysaccharide have been widely applied in biomedicine due to their outstanding biodegradability, non-toxic, and low-price. As carriers, the multi-functional chitosan hydrogels can be prepared by physical and chemical modification to form smart hydrogels to release cargoes. The smart hydrogels can generate sol-gel phase transition while gaining stimulus from the environment including pH, temperature, photo, and so forth. In recent years, a variety of therapeutic approaches such as gene therapy, chemotherapy, and combined therapy can be achieved by combining chitosan-based hydrogels with therapeutic agents.This review reports the state-of-the-art progress of chitosan-based hydrogel delivery systems and some new technologies and discusses the smart chitosan hydrogels. In addition, the current trends and the future prospects together with the drawbacks of chitosan hydrogels as biomaterials are also discussed.Chitosan as a natural material has been widely studied and reported. Due to its many advantages, the development of chitosan has been applied in all walks of life. However, the application of chitosan hydrogels in disease therapy is limited due to their weak physical and chemical properties in vivo. Thus, it is high likely that chitosan-based hydrogels will contribute to further research and exploration.

The ability to modulate the adhesion of soft materials on-demand is desired for broad applications ranging from tissue repair to soft robotics. Research effort has been focused on the chemistry and architecture of interfaces, leaving the mechanics of soft adhesives overlooked. Stimuli-responsive mechanisms of smart hydrogels could be leveraged for achieving stimuli-responsive hydrogel adhesives that respond mechanically to external stimuli. Such stimuli-responsive hydrogel adhesives involve complex chemomechanical coupling and interfacial fracture phenomena, calling for mechanistic understanding to enable rational design. Here, we combine experimental, computational, and analytical approaches to study a thermo-responsive hydrogel adhesive. Experimentally, we show that the adhesion and mechanical properties of a stimuli-responsive hydrogel adhesive are both enhanced by the application of a stimulus. Our analysis further reveals that the enhanced adhesion stems from the increased fracture energy of the bulk hydrogel and the insignificant residual stress on the adhesive-tissue interface. This study presents a framework for designing stimuli-responsive hydrogel adhesives based on the modulation of bulk properties and sheds light on the development of smart adhesives with tunable mechanics.

Tissue engineering is a promising strategy for the repair and regeneration of damaged tissues or organs. Biomaterials are one of the most important components in tissue engineering. Recently, magnetic hydrogels, which are fabricated using iron oxide-based particles and different types of hydrogel matrices, are becoming more and more attractive in biomedical applications by taking advantage of their biocompatibility, controlled architectures, and smart response to magnetic field remotely. In this literature review, the aim is to summarize the current development of magnetically sensitive smart hydrogels in tissue engineering, which is of great importance but has not yet been comprehensively viewed.

Smart hydrogels are soft materials which can be applied in sensors and actuators especially in microfluidics in which the fluid–structure interaction is important. In this work, first, the behavior of a one-way hydrogel micro-valve is investigated by considering the fluid–structure interaction effect for a specified geometry of the micro-valve. Second, both the fluid–structure interaction and non-fluid–structure interaction simulations are conducted to study the fluid flow effect on the operational parameters of the micro-valve. The obtained results show that the fluid–structure interaction effects are important and have a considerable influence on the micro-valve parameters especially on its closing temperature. Thereafter, a precise study on the micro-valve is executed by considering the micro-valve operational parameters such as inlet pressure, head size, crosslinking density, and breaking pressure at different temperatures. The results show the importance of considering the fluid–structure interaction effect in the design of these devices.

Smart hydrogels are regarded as novel sensors due to large reversible volume change in response to external stimuli. Here we prepared a novel visual multi-triggered sensor based on inverse opal hydrogel (IOH) that responses to pH, temperature and light, respectively. The hydrogel was composed of hydrophilic pH and temperature responsive poly(dimethylaminoethyl methacrylate) (PDMAEMA), and light responsive spiropyran-containing segment. When the pH decreased, the sensor changed its structural color from blue to orange-red, and the structural color was reversibly recovered by increasing pH. In addition, the color of sensor can be controlled to change from green to violet while applying a temperature field. Furthermore, the reflection peak of IOH exhibited obvious shifted behavior by UV/visible irradiation. Repeated condition changes revealed that the sensor has a long lifetime.

Pulsatile chemotherapeutic delivery profiles may provide a number advantages by maximizing the anticancer toxicity of chemotherapeutics, reducing off-target side effects, and combating adaptive resistance. While these temporally dynamic deliveries have shown some promise, they have yet to be clinically deployed from implantable hydrogels, whose localized deliveries could further enhance therapeutic outcomes. Here, several pulsatile chemotherapeutic delivery profiles were tested on melanoma cell survival in vitro and compared to constant (flatline) delivery profiles of the same integrated dose. Results indicated that pulsatile delivery profiles were more efficient at killing melanoma cells than flatline deliveries. Furthermore, results suggested that parameters like the duration of drug "on" periods (pulse width), delivery rates during those periods (pulse heights), and the number/frequency of pulses could be used to optimize delivery profiles. Optimization of pulsatile profiles at tumor sites in vivo would require hydrogel materials capable of producing a wide variety of pulsatile profiles (e.g., of different pulse heights, pulse widths, and pulse numbers). This work goes on to demonstrate that magnetically responsive, biphasic ferrogels are capable of producing pulsatile mitoxantrone delivery profiles similar to those tested in vitro. Pulse parameters such as the timing and rate of delivery during "on" periods could be remotely regulated through the use of simple, hand-held magnets. The timing of pulses was controlled simply by deciding when and for how long to magnetically stimulate. The rate of release during pulse "on" periods was a function of the magnetic stimulation frequency. These findings add to the growing evidence that pulsatile chemotherapeutic delivery profiles may be therapeutically beneficial and suggest that magnetically responsive hydrogels could provide useful tools for optimizing and clinically deploying pulsatile chemotherapeutic delivery profiles.

This review discusses basic aspects used to control the architecture and functional properties of smart hydrogels. The introduction briefly outlines what has been accomplished regarding smart hydrogels and explores historical aspects and the fundamental understanding of these systems. Then, a short discussion on the chemical interactions and the main variables involved in architectural construction is exhibited. Further analysis provides the basis for optimizing biological responses through system modulation. Finally, we outline perspectives and challenges for building smart hydrogels into functionalized and modulated delivery systems.

We report a new strategy for fabricating a smart low molecular weight hydrogel based on dynamic covalent chemistry from a bola-type supra-gelator, which was facilely fabricated in situ from two non-assembling building blocks, (3-(2-(4-formylphenoxy) ethyl)-1-methyl imidazolium bromide, MA) and (3,3'-dithiobis (propionohydrazide), DSPDZ), through dynamic acylhydrazone bonding. The obtained low molecular weight hydrogels exhibited redox-responsive and controllable self-healing properties. The role of dynamic covalent bonding in the formation of smart hydrogels is revealed in this study, which provides a simple and bottom-up method for constructing smart low molecular weight hydrogels.

In recent years, clinical applications have been proposed for various hydrogel products. Hydrogels can be derived from animal tissues, plant extracts and/or adipose tissue extracellular matrices; each type of hydrogel presents significantly different functional properties and may be used for many different applications, including medical therapies, environmental pollution treatments, and industrial materials. Due to complicated preparation techniques and the complexities associated with the selection of suitable materials, the applications of many host-guest supramolecular polymeric hydrogels are limited. Thus, improvements in the design and construction of smart materials are highly desirable in order to increase the lifetimes of functional materials. Here, we summarize different functional hydrogels and their varied preparation methods and source materials. The multifunctional properties of hydrogels, particularly their unique ability to adapt to certain environmental stimuli, are chiefly based on the incorporation of smart materials. Smart materials may be temperature sensitive, pH sensitive, pH/temperature dual sensitive, photoresponsive or salt responsive and may be used for hydrogel wound repair, hydrogel bone repair, hydrogel drug delivery, cancer therapy, and so on. This review focuses on the recent development of smart hydrogels for tissue engineering applications and describes some of the latest advances in using smart materials to create hydrogels for cancer therapy.

The emergence of smart biomaterials has significantly developed the boundaries of modern medicine. This class of biomaterials can operate as an ‘on–off’ switch for multiple applications from nanometer to macrometer scales because of their unique characteristics responsive to the environmental changes. As for illustration, smart biomaterials can guide stem cells to enhance tissue regeneration, resulting in numerous applications in tissue engineering. They can also self-fold or self-unfold to encapsulate and release cells or drugs in a controlled fashion, leading to a smart drug delivery system. Besides, the combination of stimuli-responsive biomaterials with additive manufacturing introduces smart constructs that may closely resemble natural tissues. Therefore, progress in smart biomaterials can trigger significant changes in the field of biomedical engineering. This article will briefly review the current advances and applications in smart biomaterials with emphasis on smart hydrogels, nanomaterials, bioconjugates, and shape-memory biomaterials. Furthermore, smart constructs, as well as intelligent biomaterials and systems, are summarized.

Synthesis of environmentally-sensitive, and therefore smart hydrogels of micro- and nanosize allowed substantial shortening of time of response of these gels to a change in environmental conditions. This made the hydrogels much more attractive and opened new possibilities of their applications. In this paper we present recent developments in ways of construction of micro- and nanogels, their adaptation to particular needs and possibilities of use. The focus was given to individual, spherical particles and very thin layers of gels on solid supports, including electrodes.

This review summarizes recent progress of the robust and smart hydrogels prepared from natural polymers including polysaccharides, proteins, etc. These hydrogels exhibit outstanding mechanical properties due to their nanofibrous aggregated microstructures and special crosslinking networks. Furthermore, these hydrogels show some smart stimuli-responsive behaviors triggered by pH, temperature, light, electricity and magnetism. Hopefully, these hydrogels derived from natural polymers with inherent biodegradation and biocompatibility have great application potential in the fields of biomedicine, tissue engineering, soft robots and bio-machine.

Smart hydrogels have received increasing attention for their great potential for the applications in many fields. Herein, we report a facile approach to prepare a class of dual-responsive hydrogels assembled from synthetic statistical/block thermal-responsive copoly(L-glutamate)s copolymerized with poly(ethylene glycol), which were prepared by ring-opening polymerization (ROP) and post-modification strategy. The incorporation of oligo(ethylene glycol) (OEG) and glutamic acid residues offers the gels with thermal- and pH-responsive properties simultaneously. We have systematically studied the influence of both temperature and pH on the gelation behaviors of these copolymers. It is found that the increase of glutamic acid content and solution pH values can significantly suppress the gelation ability of the samples. Circular dichroism (CD) results show that the α-helix conformation appears to be the dominant secondary conformation. More interestingly, the gelation property of the block copolymer with statistical thermal-responsive copoly(L-glutamate)s shows greater dependence on pH as compared to that with block segments due to the distinct morphology of the self-assemblies. The obtained hydrogels exhibit pH-dependent and thermal-responsive gelation behaviors, which enable them as an ideal smart hydrogel system for biomedical applications.

A laboratory experiment was developed to enable students to investigate the use of smart hydrogels for potential application in targeted drug delivery. This is challenging for students to explore practically because of the extremely high risks of handling cross-linking agents such as glutaraldehyde. Genipin is a safe and green alternative that has been combined with chitosan and poly(vinyl alcohol) to form a pH-sensitive hydrogel. In this problem-based learning mini-project, students can study the swelling behaviors, oscillatory functionality, gelation, fluorescence, optical, and release properties of this system. Students in the third year of an undergraduate chemistry degree program have successfully conducted this laboratory experiment as part of a problem-based learning mini-project.

The field of regenerative medicine has tremendous potential for improved treatment outcomes and has been stimulated by advances made in bioengineering over the last few decades. The strategies of engineering tissues and assembling functional constructs that are capable of restoring, retaining, and revitalizing lost tissues and organs have impacted the whole spectrum of medicine and health care. Techniques to combine biomimetic materials, cells, and bioactive molecules play a decisive role in promoting the regeneration of damaged tissues or as therapeutic systems. Hydrogels have been used as one of the most common tissue engineering scaffolds over the past two decades due to their ability to maintain a distinct 3D structure, to provide mechanical support for the cells in the engineered tissues, and to simulate the native extracellular matrix. The high water content of hydrogels can provide an ideal environment for cell survival, and structure which mimics the native tissues. Hydrogel systems have been serving as a supportive matrix for cell immobilization and growth factor delivery. This review outlines a brief description of the properties, structure, synthesis and fabrication methods, applications, and future perspectives of smart hydrogels in tissue engineering.

Understanding structure-property relationships is critical for the development of new drug delivery systems. This study investigates the properties of Pluronic smart hydrogel formulations for future use as injectable controlled drug carriers. The smart hydrogels promise to enhance patient compliance, decrease side effects and reduce dose and frequency. Pharmaceutically, these systems are attractive due to their unique sol-gel phase transition in the body, biocompatibility, safety and injectability as solutions before transforming into gel matrices at body temperature. We quantify the structural changes of F127 systems under controlled temperature after flow, as experienced during real bodily injection. Empirical formulae combining the coupled thermal and shear dependency are produced to aid future application of these systems. Induced structural transitions measured in-situ by small angle x-ray and neutron scattering reveal mixed oriented structures that can be exploited to tailor the drug release profile.

Soft materials can be manufactured into soft micro-robots for biomedical applications. Especially, hydrogels provided potentials for loading drugs and delivering them to target controlled by pH or electric field. By application of photoinitiator, these hydrogels can be manufactured into complex 3D structures. Compared to the traditional gelling methods, the gelling process used in 3D printing changed some mechanical properties of these hydrogels. Therefore, it is necessary to study the mechanical properties and drug delivery performance of these hydrogels if we want to use them as biomaterials and 3D printed micro-robots. Here, we focused on the mechanical properties and drug delivery performance of an electric controlled smart hydrogel which has the ability to be printed into complex 3D structures. Electric controlled smart hydrogels were studied with different photoinitiators, and the results provide guidance for the application of printable smart hydrogels.

Hydrogels prepared from natural polymers have received immense considerations over the past decade due to their safe nature, biocompatibility, hydrophilic properties, and biodegradable nature. More recently, when treated with electroactive materials, these hydrogels were endowed with high electrical conductivity, electrochemical redox properties, and electromechanical properties; consequently, forming a smart hydrogel. The biological properties of these smart hydrogels, classified as electroconductive hydrogels, can be combined with electronics. Thus, they are considered as good candidates for some potential uses, which include bioconductors, biosensors, electro-stimulated drug delivery systems, as well as neuron-, muscle-, and skin-tissue engineering. However, there is lacking comprehensive information on the current state of these electroconductive hydrogels which complicates our understanding of this new type of biomaterials as well as their potential applications. Hence, this review provides a summary on the current development of electroconductive natural polymer-based hydrogels (ENPHs). We have introduced various types of ENPHs, with a brief description of their advantages and shortcomings. In addition, emerging technologies regarding their synthesis developed during the past decade are discussed. Finally, two attractive potential applications of ENPHs, cell culture and biomedical devices, are reviewed, along with their current challenges.

Smart hydrogels that respond to magnetic fields have attracted increasing interest in recent years. This is as a result of their numerous potential applications such as tunable delivery vehicles, magnetic resonance imaging contrast agents, hyperthermal therapy agents, etc. In this review, we summarize the methods for preparing magnetic hydrogels. Then we give an overview of magnetic hydrogels with various applications. Finally, the current limitations in the preparation and application of magnetic hydrogels are discussed and perspectives will be proposed for the next generation of hydrogels. © 2016 Society of Chemical Industry

A facile polymer-assisted method achieves simultaneous exfoliation and noncovalent functionalization of MoSe2 nanosheets. The nanosheet dispersion can further assemble into a novel "smart" nanocomposite hydrogel, whose dual-responsive (photo- and thermoresponsive) behavior is reversible and can be controllably tailored by varying the distribution of hydrophilic and hydrophobic groups in the polymer.

Development of polymer-based smart materials, which can autonomously alter their physical and/or chemical properties when exposed to external stimuli, is a thriving research frontier in contemporary advanced functional materials science. Poly(N-isopropylacrylamide) (PNIPAM)-based smart hydrogels are known to exhibit distinct thermo-responsive properties near a lower critical solution temperature (LCST), which have found diverse promising applications such as smart coating, drug delivery, tissue regeneration, and artificial muscles. In this review, we provide an up-to-date account on the recent developments in advanced functional PNIPAM-based smart hydrogels and their emerging technological applications in the fields of smart actuators, photonic crystals, smart windows and novel biomedical applications. The fundamental design and synthetic strategies of PNIPAM-based smart hydrogels are discussed. Their unique properties, underlying mechanisms and potential applications in different fields are highlighted. Finally, this review provides a brief conclusion and enumerates the challenges and opportunities in this rising area of research and development involving these intriguing polymer-based advanced smart systems rooted in chemistry and materials science. It is expected that this review would provide significant insights for the development of reconfigurable and programmable advanced smart materials with numerous possibilities, prompting the rapid advancement of this highly interdisciplinary area, which encompasses materials science, polymer science, synthetic chemistry, device engineering, physics, biology, nanoscience and nanotechnology.

The area of interest is the synthesis and study of properties of new types of hydrogels made from pelt waste, in order to recover waste from tanneries. Leather processing in tanneries results in about 500-600 kg of pelt waste from a ton of raw hides. These hydrogels are made using smart processes in order to then be applied in agriculture, for preservation of water in the soil or for controlled release of fertilizers, pesticides but also for the development of additivated agricultural film biodegradable over time (between 1 month and 6 months). Hydrogels that are based on biopolymers, compared with hydrogels based on synthetic polymers, have the advantage of biodegradability, biocompatibility, and a low level of toxicity. The paper presents the production of biodegradable polymer mixtures obtained from hydrolysis and enrichment of the resulting hydrolysate with phosphorus and potassium. Hydrogels with collagenous structure are tested using a high-performance instrumental analysis system (FT-IR-ATR, UV-Vis-NIR, SEM, EDAX, etc). The paper presents an experimental model for obtaining hydrogels with collagenous structure from pelt waste resulting from the liming process.

There is a strong commercial need for inexpensive point-of-use sensors for monitoring disease biomarkers or environmental contaminants in drinking water. Point-of-use sensors that employ smart polymer hydrogels as recognition elements can be tailored to detect almost any target analyte, but often suffer from long response times. Hence, we describe here a fabrication process that can be used to manufacture low-cost point-of-use hydrogel-based microfluidics sensors with short response times. In this process, mask-templated UV photopolymerization is used to produce arrays of smart hydrogel pillars inside sub-millimeter channels located upon microfluidics devices. When these pillars contact aqueous solutions containing a target analyte, they swell or shrink, thereby changing the resistance of the microfluidic channel to ionic current flow when a small bias voltage is applied to the system. Hence resistance measurements can be used to transduce hydrogel swelling changes into electrical signals. The only instrumentation required is a simple portable potentiostat that can be operated using a smartphone or a laptop, thus making the system suitable for point of use. Rapid hydrogel response rate is achieved by fabricating arrays of smart hydrogels that have large surface area-to-volume ratios.

This paper presents two novel techniques for monitoring the response of smart hydrogels composed of synthetic organic materials that can be engineered to respond (swell or shrink, change conductivity and optical properties) to specific chemicals, biomolecules or external stimuli. The first technique uses microwaves both in contact and remote monitoring of the hydrogel as it responds to chemicals. This method is of great interest because it can be used to non-invasively monitor the response of subcutaneously implanted hydrogels to blood chemicals such as oxygen and glucose. The second technique uses a metal-oxide-hydrogel field-effect transistor (MOHFET) and its associated current-voltage characteristics to monitor the hydrogel&rsquo, s response to different chemicals. MOHFET can be easily integrated with on-board telemetry electronics for applications in implantable biosensors or it can be used as a transistor in an oscillator circuit where the oscillation frequency of the circuit depends on the analyte concentration.

Well-defined amphiphilic triblock poly(sodium methacrylate)-polystyrene-poly(sodium methacrylate) (PMAA-b-PS-b-PMAA) copolymers characterized by a different length of either the hydrophilic or the hydrophobic block have been synthesized by ATRP. In solution the micelle-like aggregates consist of a collapsed PS core surrounded by stretched charged PMAA chains. The micelles are kinetically ‘frozen’ and as a consequence the triblock copolymers do not show a significant surface activity. The hydrophilic block length has a major influence on the rheology, the shortest PMAA blocks yielding the strongest gels (at the same total weight concentration). The hydrophobic block length has only a minor influence until a certain threshold, below which the hydrophobic interactions are too weak resulting in weak gels. A mathematical model is used to describe the micelle radius and the results were in good agreement with the experimentally found radius in transmission electron microscopy. The influences of the ionic strength, pH and temperature on the rheology has also been investigated, showing the potential of these polymers as smart hydrogels. The change in conformation of the hydrophilic corona from the collapsed state to the stretched state by changing the pH was quantified with zeta-potential measurements. To the best of our knowledge, this is the first systematic investigation of this kind of triblock copolymers in terms of their rheological behavior in water.

The physiological milieu of healthy skin is slightly acidic, with a pH value between 4 and 6, whereas for skin with chronic or infected wounds, the pH value is above 7.3. As testing pH value is an effective way to monitor the status of wounds, a novel smart hydrogel wound patch incorporating modified pH indicator dyes was developed in this study. Phenol red (PR), the dye molecule, was successfully modified with methacrylate (MA) to allow a copolymerization with the alginate/polyacrylamide (PAAm) hydrogel matrix. This covalent attachment prevented the dye from leaching out of the matrix. The prepared pH-responsive hydrogel patch exhibited a porous internal structure, excellent mechanical property, and high swelling ratio, as well as an appropriate water vapour transmission rate. Mechanical responses of alginate/P(AAm-MAPR) hydrogel patches under different calcium and water contents were also investigated to consider the case of exudate accumulation into hydrogels. Results showed that increased calcium amount and reduced water content significantly improved the Young's modulus and elongation at break of the hydrogels. These characteristics indicated the suitability of hydrogels as wound dressing materials. When pH increased, the color of the hydrogel patches underwent a transition from yellow (pH 5, 6 and 7) to orange (7.4 and 8), and finally to red (pH 9). This range of color change matches the clinically-meaningful pH range of chronic or infected wounds. Therefore, our developed hydrogels could be applied as promising wound dressing materials to monitor the wound healing process by a simple colorimetric display, thus providing a desirable substrate for printed electronics for smart wound dressing.

During the past few decades, thiomers have attracted interest as responsive-polymers in the design of smart hydrogels, due to thiol reactivity to physical stimuli (i.e., pH, oxygen, UV/Vis irradiation). However, thiomer potentialities have been limited by their low thiolation degree and lack of multi-responsiveness to physical cues. In this work, a new class of thiomers with tailored thiolation degree and sensitivity to multiple physical stimuli was developed. To this aim, a polyurethane (33,000 Da) was synthesised from Poloxamer® 407, 1,6-diisocyanatohexane and N-Boc diethanolamine. Secondary amino groups were exposed through Boc-removal (yield 80%, assessed by 1H NMR) giving up to 4.5 × 1020 ± 1.8 × 1019 –NH units/gpolymer (Orange II Sodium Salt colorimetric assay) without polymer chemical degradation. Polymer thermo-responsiveness was proved by the increase in micelle hydrodynamic diameter upon system heating up to 45 °C and through estimated critical micellar temperatures. Thioglycolic acid grafting to exposed amines via carbodiimide chemistry was optimised to give up to 1.73 × 1019 thiols/gpolymer (Ellman's method), while minimising disulphide bond formation. Finally, the best storage conditions against oxidation were investigated by quantifying free thiols at different time points.

The latest development in the field of smart hydrogels application as drugs carriers is shown in this chapter. Hydrogels are three-dimensional polymer network consisting of at least one hydrophilic monomer. They are insoluble in water, but in the excess presence of water or physiological fluids, swell to the equilibrium state. The amount of absorbed water depends on the chemical composition and the crosslinking degree of 3D hydrogel network and reaches over 1000% of the xerogel weight. Stimuli-responsive hydrogels exhibit significant change of their properties (swelling, color, transparency, conductivity, shape) due to small changes in the external environment conditions (pH, ionic strength, temperature, light wavelength, magnetic or electric fields, ultrasound, or a combination thereof). This smart hydrogels, with different physical and chemical properties, chemical structure and technology of obtaining, show great potential for application in the pharmaceutical industry. The application of smart hydrogels is very promising and at the beginning of the development and exploitation.

The ability of hydrophilic chain segments in polymer networks to strongly interact with water allows the volumetric expansion of the material and formation of a hydrogel. When polymer chain segments undergo reversible hydration depending on environmental conditions, smart hydrogels can be realized, which are able to shrink/swell and thus alter their volume on demand. In contrast, implementing the capacity of hydrogels to switch their shape rather than volume demands more sophisticated chemical approaches and structural concepts. In this Account, the principles of hydrogel network design, incorporation of molecular switches, and hydrogel microstructures are summarized that enable a spatially directed actuation of hydrogels by a shape-memory effect (SME) without major volume alteration. The SME involves an elastic deformation (programming) of samples, which are temporarily fixed by reversible covalent or physical cross-links resulting in a temporary shape. The material can reverse to the original shape when these molecular switches are affected by application of a suitable stimulus. Hydrophobic shape-memory polymers (SMPs), which are established with complex functions including multiple or reversible shape-switching, may provide inspiration for the molecular architecture of shape-memory hydrogels (SMHs), but cannot be identically copied in the world of hydrophilic soft materials. For instance, fixation of the temporary shape requires cross-links to be formed also in an aqueous environment, which may not be realized, for example, by crystalline domains from the hydrophilic main chains as these may dissolve in presence of water. Accordingly, dual-shape hydrogels have evolved, where, for example, hydrophobic crystallizable side chains have been linked into hydrophilic polymer networks to act as temperature-sensitive temporary cross-links. By incorporating a second type of such side chains, triple-shape hydrogels can be realized. Considering the typically given light permeability of hydrogels and the fully hydrated state with easy permeation by small molecules, other types of stimuli like light, pH, or ions can be employed that may not be easily used in hydrophobic SMPs. In some cases, those molecular switches can respond to more than one stimulus, thus increasing the number of opportunities to induce actuation of these synthetic hydrogels. Beyond this, biopolymer-based hydrogels can be equipped with a shape switching function when facilitating, for example, triple helix formation in proteins or ionic interactions in polysaccharides. Eventually, microstructured SMHs such as hybrid or porous structures can combine the shape-switching function with an improved performance by helping to overcome frequent shortcomings of hydrogels such as low mechanical strength or volume change upon temporary cross-link cleavage. Specifically, shape switching without major volume alteration is possible in porous SMHs by decoupling small volume changes of pore walls on the microscale and the macroscopic sample size. Furthermore, oligomeric rather than short aliphatic side chains as molecular switches allow stabilization of the sample volumes. Based on those structural principles and switching functionalities, SMHs have already entered into applications as soft actuators and are considered, for example, for cell manipulation in biomedicine. In the context of those applications, switching kinetics, switching forces, and reversibility of switching are aspects to be further explored.

Biomedical research, known as medical research, is conducive to support and promote the development of knowledge in the field of medicine. Hydrogels have been extensively used in many biomedical fields due to their highly absorbent and flexible properties. The smart hydrogels, especially, can respond to a broad range of external stimuli such as temperature, pH value, light, electric and magnetic fields. With excellent biocompatibility, tunable rheology, mechanical properties, porosity, and hydrated molecular structure, hydrogels are considered as promising candidate for simulating local tissue microenvironment. In this review article, we mainly focused on the most recent development of engineering synthetic hydrogels; moreover, the classification, properties, especially the biomedical applications including tissue engineering and cell scaffolding, drug and gene delivery, immunotherapies and vaccines, are summarized and discussed.

A novel and facile assembly strategy has been successfully developed to construct smart nanocomposite (NC) hydrogels with inhomogeneous structures using nanoclay-cross-linked stimuli-responsive hydrogel subunits as building blocks via rearranged hydrogen bonding between polymers and clay nanosheets. The assembled thermoresponsive poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAM-co-AM)) hydrogels with various inhomogeneous structures exhibit excellent mechanical properties due to plenty of new hydrogen bonding interactions created at the interface for locking the NC hydrogel subunits, which are strong enough to tolerate external forces such as high levels of elongations and multicycles of swelling/deswelling operations. The proposed approach is featured with flexibility and designability to build assembled hydrogels with diverse architectures for achieving various responsive deformations, which are highly promising for stimuli-responsive manipulation such as actuation, encapsulation, and cargo transportation. Our assembly strategy creates new opportunities for further developing mechanically strong hydrogel systems with complex architectures that composed of diverse internal structures, multistimuli-responsive properties, and controllable shape deformation behaviors in the soft robots and actuators fields.

Smart hydrogels are promising materials for actuators and sensors, as they can respond to small changes in their environment with a large property change. Hydrogels can respond to a variety of stimuli, for example temperature, pH, metal ions, etc. In this article, the synthesis and characterization of polyampholyte hydrogels based on open chain ligands showing pH and metal ion sensitivity are described. Copolymer and terpolymer gels using different mixtures of monomers i.e., N-[2-(dimethylaminoethyl)acrylamide] (DMAEAAm), N,N-dimethylacrylamide (DMAAm), acrylic acid (AA) and 2-acrylamido-2-methyl-1-propanesulphonic acid (AMPS), have been synthesized. The effect of copolymer composition, i.e., the ratio and amount of ionic monomers and the degree of crosslinking on the swelling characteristics, was evaluated as a function of pH. On this basis, metal ion sensitivity measurements were performed at selected pH values. The metal ion sensitivity was measured by varying the concentration of Cu2+, Zn2+ and Ag+ ions under acidic pH conditions.

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.

Smart hydrogels are useful elements in microfluidic systems because they respond to environmental stimuli and are capable of storing reagents. We present here a concept of using hydrogels (poly(N-isopropylacrylamide)) as an interface between continuous and discontinuous microfluidics. Their swelling and shrinking capabilities allow them to act as storage elements for reagents absorbed in the swelling process. When the swollen hydrogel collapses in an oil-filled channel, the incorporated water and molecules are expelled from the hydrogel and form a water reservoir. Water-in-oil droplets can be released from the reservoir generating different sized droplets depending on the flow regime at various oil flow rates (dispensing functionality). Different hydrogel sizes and microfluidic structures are discussed in terms of their storage and droplet formation capabilities. The time behaviour of the hydrogel element is investigated by dynamic swelling experiments and computational fluid dynamics simulations. By precise temperature control, the device acts as an active droplet generator and converts continuous to discontinuous flows.

Recent advances and applications of biomolecule-responsive hydrogels, namely, glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid-responsive hydrogels are highlighted. However, achieving the ultimate purpose of using biomolecule-responsive hydrogels in preclinical and clinical areas is still at the very early stage and calls for more novel designing concepts and advance ideas. On the way toward the real/clinical application of biomolecule-responsive hydrogels, plenty of factors should be extensively studied and examined under both in vitro and in vivo conditions. For example, biocompatibility, biointegration, and toxicity of biomolecule-responsive hydrogels should be carefully evaluated. From the living body's point of view, biocompatibility is seriously depended on the interactions at the tissue/polymer interface. These interactions are influenced by physical nature, chemical structure, surface properties, and degradation of the materials. In addition, the developments of advanced hydrogels with tunable biological and mechanical properties which cause no/low side effects are of great importance.

pH- and temperature-sensitive hydrogels, based on 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) copolymers, were prepared by gamma-irradiation and characterized in order to examine their potential use in biomedical applications. The influence of comonomer ratio in these smart copolymers on their morphology, mechanical and thermal properties, biocompatibility and microbe penetration capability was investigated. The mechanical properties of copolymers were investigated using the dynamic mechanical analysis (DMA), while their thermal properties and morphology were examined by thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The morphology, mechanical and thermal properties of these hydrogels were found to be suitable for most requirements of biomedical applications. The in vitro study of P(HEMA/IA) biocompatibility showed no evidence of cell toxicity nor any considerable hemolytic activity. Furthermore, the microbe penetration test showed that neither Staphylococcus aureus nor Escherichia coli passed through the hydogel dressing; thus the P(HEMA/IA) dressing could be considered a good barrier against microbes. All results indicate that stimuli-responsive P(HEMA/IA) hydrogels have great potential for biomedical applications, especially for skin treatment and wound dressings. (C) 2009 Elsevier Ltd. All rights reserved.