Intelligent Hydrogels

An Introduction to Hydrogels and Some Recent Applications
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Both acidic and basic polymers are employed in pH-sensitive DDS.


Thermosensitive polymers, like pH-responsive systems, offer many possibilities in biomedicine. Heavy metal pollution is commonly found in wastewater of many industrial processes and has been known to cause severe threats to the public health and ecological systems.

The removal of heavy metal ions from various water resources is of great scientific and practical interest. Synthetic cross-linked polyacrylate hydrogels have been used to remove heavy metal toxicity from aqueous media [ 27 ]. However, application of these synthetic materials on large scales may not be a practical solution because they are very costly. The pollution caused by heavy metal ions can be removed by well-known adsorption processes which, alongside flexibility in design and operation, offer the advantage of reusing the treated effluent.

Also because of general reversibility of adsorption process, it is usually possible to regenerate the adsorbent to make the process most cost-effective. The use of hydrogels as adsorbents for the removal of heavy metals, recovery of dyes, and removal of toxic components from various effluents has been studied.

Adsorbents with carboxyl, sulfonic, phosphonic, and nitrogen groups on their surface favor metal ion adsorption [ 77 ]. The hydrogels were proven to be excellent dye adsorbent materials with extremely high amounts of methylene blue adsorption. Many applications of polyelectrolytes in this area are due to their ability to bind oppositely charged metal ions to form complexes. In fact, having both cationic and anionic charges on the micro- or nano-gel provides additional advantages for the removal of two distinct species simultaneously.

Hydrogels are versatile and viable materials that show potential for environmental applications. Chitosan, alginate, starch, and cellulose derivatives are biopolymer-based hydrogels, which were used to remove metal ions from aqueous media. It has been shown that the sorption mechanism and sorption capacity of heavy metal ions were influenced by the functional groups of the hydrogel.

This is because of the participation of other processes like chelating and ion exchange rather than simple sorption in removal of metal ions [ 78 , 79 ]. Chitosan-based hydrogels are applicable in the removal of heavy metal ions due to the presence of multiple amino NH 2 and hydroxyl OH groups in their structure.

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This applicability originates from the tendency of metal ions to form chelates with the so-called amino groups. But after reaction of chitosan with cross-linkers, its alkalescence which is related to adsorption capacity is decreased. Chemical modification of these functional groups can improve not only the adsorption capacity but also the physicochemical properties of chitosan [ 79 , 80 ].

Different approaches were employed by researchers to modify chitosan including the use of amino acid esters, oxoglutaric acid, pyridyl, ethylenediamine, carbodiimide, aromatic polyimides, amine-functionalized magnetic nanoparticles, and glycine [ 81 — 83 ]. It is shown in these studies that both adsorption capacity and mechanical resistance of chitosan-based hydrogels will improve after modification of functional groups.

Tissue engineering is defined as a combination of materials, engineering, and cells to improve or replace biological organs. This needs finding proper types of cells and culturing them in a suitable scaffold under appropriate conditions. Hydrogels are an appealing scaffold material because their structures are similar to the extracellular matrix of many tissues, they can often be processed under relatively mild conditions, and they may be delivered in a minimally invasive manner [ 32 ]. Adequate scaffold design and material selection for each specific application depends on several variables, including physical properties, mass transport properties, and biological properties and is specified by the intended scaffold application and environment into which the scaffold will be placed.

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For example, the type of scaffold used to produce artificial skin must be different from that used for artificial bone and thus different structures for materials are needed. Both synthetic and naturally derived materials can be used to form hydrogels for tissue engineering scaffolds. Synthetic hydrogels are interesting because it is easy to control their chemistry and structure and thus alter their properties.

Naturally derived hydrogel-forming polymers are other candidates for use in tissue engineering scaffolds because they either are natural extracellular matrix components or have properties similar to these matrices and they interact in a favorable manner in vivo. Hydrogels are used for three purposes in tissue engineering applications. They may be used as agents for filling vacant spaces, carriers for delivery of bioactive molecules, and 3D structures that act as a support for cells and help the formation of an ideal tissue.

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Agents for filling vacant spaces space-filling agents include scaffolds that provide bulking, prevent adhesions, or act as bioadhesives [ 33 ]. To reach this aim, the most basic design requirements for a hydrogel are the abilities to keep a desired volume and structural integrity for the required time. Hydrogel scaffolds based on alginate, chitosan, and collagen show potential for use as general bulking agents.

Synthetic hydrogels are often used as anti-adhesive materials because cells lack adhesion receptors to them and proteins often do not readily absorb to them if designed appropriately. Polyethylene glycol PEG has been used to prevent post-operative adhesions [ 32 , 33 ].

Hydrogels composed of chitosan and chitin derivatives are now used as biological adhesives in surgical procedures to seal small wounds out of which air and body fluids could leak, and to improve the effectiveness of wound dressings [ 37 , 38 ]. Another application of scaffold hydrogels that is quite different includes using them as vehicles to stabilize and deliver bioactive molecules to the target tissues and to encapsulate secretory cells. Currently, most drugs are delivered into patients systemically without the use of a scaffold, so large doses are usually required for a desired local effect because of enzymatic degradation of the drug and nonspecific uptake by other tissues.

This is a costly process and can cause serious side effects. In addition, many factors, which are necessary or beneficial to the target tissue, may be toxic to other tissues. Thus, a vehicle or scaffold allowing for local and specific delivery to the desired tissue site is highly desirable in many situations. Ionically cross-linked alginate hydrogels and glutaraldehyde cross-linked collagen sponges are some of the examples to fulfill this requirement [ 39 , 40 ].

As hydrogels are highly hydrated 3D networks of polymers, they can provide chemical and mechanical signals and also an environment for cells to adhere, proliferate, and differentiate; thus, they are suitable for cell delivery and tissue development goals.

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Nowadays, hydrogel scaffolds are being used to produce a wide range of tissues, including cartilage, bone, muscle, fat, liver, and neurons. Based on the type of the desired tissue, different kinds of hydrogels can be utilized. For example, alginate has been used more widely than other hydrogels to assess the in vivo potential of hydrogel scaffolds for cartilage engineering and also as Schwann cell matrices in the area of nerve grafting, and collagen has been used for engineering large blood vessels [ 33 ].


Nowadays, hydrogels have attracted a growing interest of many scientists in different fields of research. Intelligent hydrogels have found a significant role in a . This volume of Progress in Colloid and Polymer Science assembles original contributions and invited reviews from the priority research program "Intelligent.

A key area in the use of synthetic hydrogels for bioapplications is ophthalmology, especially contact lenses. A contact lens is a small optical device placed directly on the cornea to alter the corneal power. The first concept of using contact lenses was described by Leonardo da Vinci in ; this consisted of immersing the eye in a bowl of water. Direct placing of contact lenses on the surface of cornea prevents the exchange of atmospheric oxygen and thus disturbs the natural physiological metabolism of the cornea known as hypoxic stress, so a good contact lens must have maximum oxygen permeability.

Mechanical stress to the cornea produces the same problems as the hypoxic stress, such as mitosis of the epithelial cells, elevated activity in protease and glycosidase, corneal sensitivity, and changes in corneal hydration and transparency. To reduce these stresses, the proper choice of contact materials and their shape are necessary. Hydrogels used for production of contact lenses can cover most of the requirements needed when using in different physiological conditions. For a hydrogel material that is used as a contact lens, there are some necessities to make it comfortable during usage.

These necessities include amount of water content, good mechanical properties, permeability toward oxygen, wettability of surface, good optical facilities, stability toward hydrolysis and sterilization, having nontoxic nature, and having enough biological tolerance for living cells. In order to increase the water content of hydrogel and achieve an enhanced swelling effect, different types of monomers can be used. These include dihydroxy methacrylates, methacrylic acid, acrylamides, and many other monomers.

Silicone hydrogels represent an independent group of contact lens materials. The evolution of basic hydrogels gave rise to the production of this class, and they have good swelling properties and high permeability toward oxygen, which make them suitable for use in lenses. These properties are owing to their structure in which hydrophobic silicones are connected with hydrophilic chains in such a way that makes the resulting composite suitable both mechanically and optically. It is possible to incorporate linear or branched hydrophilic polymer chains into the structure of the polymer to form an interpenetrated network to reduce the drying by the lenses when using them normally.

Stimuli-responsive polymers or hydrogels can change their volume significantly in response to small alterations of certain environmental parameters. Cationic polyelectrolytes dissolve swell more at low pH and anionic polyelectrolytes vice versa and this is due to ionization [ 44 ]. Two types of transducers are used in pH-sensitive hydrogel sensors: transducers based on mechanical work performed by hydrogel swelling and shrinking and those observing changes in properties of free swelling gels [ 45 ]. The ability of hydrogels to deform or to strain mechanically a transduction element resulting in a change of a special property of that element or in a change of a detectable distance is the basis of operation of transducers based on mechanical work of the hydrogel.

They are classified as optical transducers, including reflective diaphragms and fiber Bragg grating sensors, and mechanical transducers, including microcantilevers and bending plate transducers. Transducers of free swelling gels have to directly observe changes in one or more hydrogel properties and include optical, conductometric, and oscillating transducers. Optical transducers can directly measure changes in optical properties of hydrogels. A different approach is based on the observation of special fillings or surface coatings, which are changed or moved due to hydrogel swelling.

Oscillating transducers are devices that keep changing their resonance frequency. Changes in the properties of a load result in a shift of this resonance frequency.

Intelligent Hydrogels

This can be accompanied by a change of the signal amplitude. Conductometric transducers are based on measuring the conductivity of hydrogel as the degree of swelling changes [ 44 ]. Combining physical and chemical sensors results in a biosensor. There are two definitions for what a biosensor can do: it can be thought as a device that can sense and report a biophysical property of the system under study or a device that can deliver useful analytical information from transforming biochemical data. A common aspect in all biosensors is the presence of a biological recognition part that makes it possible to analyze biological information.

Biosensors are becoming increasingly important as practical tools to cover a wide variety of application areas including point-of-care testing, home diagnostics, and environmental monitoring. Biological recognition part known as bioelement consists of different structures like enzymes, antibodies, living cells, or tissues but the point is its specificity toward one analyte and zero response to other interferents. There are various methods for coupling biomolecules with sensors including entrapment into membranes, physical adsorption, entrapment into a matrix, or covalent bonding [ 42 , 44 ].

The high water content and hydrophilic nature of hydrogels are similar to the void-filling component of the extracellular matrix and render them intrinsically biocompatible. Hence, an apparent application of hydrogels in biosensors is the protection and coating function of sensor parts to prevent undesired interaction with biological molecules or cells.

Hydrogels can be used as immobilization matrices for the biosensing elements and provide excellent environments for enzymes and other biomolecules to preserve their active and functional structure. Several types of sensing elements are used based on the nature of analyte but these elements can be categorized in two distinct groups: molecular interactions and living sensors.