A hydrogel is a network of crosslinked polymer chains that are hydrophilic, sometimes found as a colloidal gel in which water is the dispersion medium. A three-dimensional solid results from the hydrophilic polymer chains being held together by cross-links. The crosslinks which bond the polymers of a hydrogel fall under two general categories: physical and chemical. Physical crosslinks consist of hydrogen bonds, hydrophobic interactions, and chain entanglements (among others). Because of the inherent cross-links, the structural integrity of the hydrogel network does not dissolve from the high concentration of water. Hydrogels are highly absorbent (they can contain over 90% water) natural or synthetic polymeric networks.
The first appearance of the term 'hydrogel' in the literature was in 1894.
Common uses include:
- Scaffolds in tissue engineering. When used as scaffolds, hydrogels may contain human cells to repair tissue. They mimic 3D microenvironment of cells.
- Hydrogel-coated wells have been used for cell culture.
- Investigating biomechanical functions in cells when combined with Holotomography microscopy
- Environmentally sensitive hydrogels (also known as 'Smart Gels' or 'Intelligent Gels'). These hydrogels have the ability to sense changes of pH, temperature, or the concentration of metabolite and release their load as result of such a change.
- Injectable hydrogels which can be used as drug carriers for treatment of diseases or as cell carriers for regenerative purposes or tissue engineering.
- Sustained-release drug delivery systems. Ionic strength, pH and temperature can be used as a triggering factor to control the release of the drug.
- Providing absorption, desloughing and debriding of necrotic and fibrotic tissue
- Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors, as well as in DDS.
- Disposable diapers where they absorb urine, or in sanitary napkins
- Contact lenses (silicone hydrogels, polyacrylamides, polymacon)
- EEG and ECG medical electrodes using hydrogels composed of cross-linked polymers (polyethylene oxide, polyAMPS and polyvinylpyrrolidone)
- Water gel explosives
- Rectal drug delivery and diagnosis
- Encapsulation of quantum dots
- Breast implants
- Granules for holding soil moisture in arid areas
- Dressings for healing of burn or other hard-to-heal wounds. Wound gels are excellent for helping to create or maintain a moist environment.
- Reservoirs in topical drug delivery; particularly ionic drugs, delivered by iontophoresis (see ion exchange resin).
- Materials mimicking animal mucosal tissues to be used for testing mucoadhesive properties of drug delivery systems
- Thermodynamic electricity generation. When combined with ions allows for heat dissipation for electronic devices and batteries and converting the heat exchange to an electrical charge.
Common ingredients include polyvinyl alcohol, polyethylene glycol, sodium polyacrylate, acrylate polymers and copolymers with an abundance of hydrophilic groups, and natural proteins such as collagen, gelatin and fibrin.
The crosslinks which bond the polymers of a hydrogel fall under two general categories: physical and chemical. Physical crosslinks consist of hydrogen bonds, hydrophobic interactions, and chain entanglements (among others). A hydrogel generated through the use of physical crosslinks is sometimes called a ‘reversible’ hydrogel. Chemical crosslinks consist of covalent bonds between polymer strands. Hydrogels generated in this manner are sometimes called ‘permanent’ hydrogels.
One notable method of initiating a polymerization reaction involves the use of light as a stimulus. In this method, photoinitiators, compounds that cleave from the absorption of photons, are added to the precursor solution which will become the hydrogel. When the precursor solution is exposed to a concentrated source of light, the photoinitiators will cleave and form free radicals, which will begin a polymerization reaction that forms crosslinks between polymer strands. This reaction will cease if the light source is removed, allowing the amount of crosslinks formed in the hydrogel to be controlled. The properties of a hydrogel are highly dependent on the type and quantity of its crosslinks, making photopolymerization a popular choice for fine-tuning hydrogels. This technique has seen considerable use in cell and tissue engineering applications due to the ability to inject or mold a precursor solution loaded with cells into a wound site, then solidify it in situ.
Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. As responsive "smart materials," hydrogels can encapsulate chemical systems which upon stimulation by external factors such as a change of pH may cause specific compounds such as glucose to be liberated to the environment, in most cases by a gel-sol transition to the liquid state. Chemomechanical polymers are mostly also hydrogels, which upon stimulation change their volume and can serve as actuators or sensors.
A short-peptide-based hydrogel matrix, capable of holding about one hundred times its own weight in water. Developed as a medical dressing. The thickness of the fibers was on the order of tens of nm, mimicking the fibrous microenvironment found in the extracellular matrix. Field emission scanning electron microscopy image
Hydrogels possess a vast range of mechanical properties, which is one of the primary reasons why they have recently been investigated for a wide spread of applications. By modifying the polymer concentration of a hydrogel (or conversely, the water concentration), the Young’s Modulus, Shear Modulus, and Storage Modulus can vary from 10 Pa to 3 MPa, a range of about five orders of magnitude. A similar effect can be seen by altering the crosslinking concentration. This much variability of the mechanical stiffness is why hydrogels are so appealing for biomedical applications, where it is vital for implants to match the mechanical properties of the surrounding tissues.
In the unswollen state, hydrogels can be modelled as highly crosslinked chemical gels, in which the system can be described as one continuous polymer network. In this case:
where G is the shear modulus, k is the Boltzmann constant, T is temperature, Np is the number of polymer chains per unit volume, ρ is the density, R is the ideal gas constant, and is the (number) average molecular weight between two adjacent cross-linking points. can be calculated from the swell ratio, Q, which is relatively easy to test and measure.
For the swollen state, a perfect gel network can be modeled as:
In a simple uniaxial extension or compression test, the true stress, , and engineering stress, , can be calculated as:
where is the stretch.
In order to describe the time-dependent creep and stress-relaxation behavior of hydrogel, a variety of physical lumped parameter models can be used. These modeling methods vary greatly and are extremely complex, so the empirical Prony Series description is commonly used to describe the viscoelastic behavior in hydrogels.
The most commonly seen environmental sensitivity in hydrogels is a response to temperature. Many polymers/hydrogels exhibit a temperature dependent phase transition, which can be classified as either an Upper Critical Solution Temperature (UCST) or Lower Critical Solution Temperature (LCST). UCST polymers increase in their water-solubility at higher temperatures, which lead to UCST hydrogels transitioning from a gel (solid) to a solution (liquid) as the temperature is increased (similar to the melting point behavior of pure materials). This phenomenon also causes UCST hydrogels to expand (increase their swell ratio) as temperature increases while they are below their UCST. However, polymers with LCSTs display an inverse (or negative) temperature-dependence, where their water-solubility decreases at higher temperatures. LCST hydrogels transition from a liquid solution to a solid gel as the temperature is increased, and they also shrink (decrease their swell ratio) as the temperature increases while they are above their LCST.
Different applications call for different thermal responses. For example, in the biomedical field, LCST hydrogels are being investigated as drug delivery systems due to being injectable (liquid) at room temp and then solidifying into a rigid gel upon exposure to the higher temperatures of the human body. There are many other stimuli that hydrogels can be responsive to, including: pH, glucose, electrical signals, light, pressure, ions, antigens, and more.
There are many ways to fine-tune the mechanical properties of hydrogels. One of the most simple is to use different molecules for the backbone and crosslinkers of the hydrogel system, as different molecules will have different intermolecular interactions with each other and different interactions with the absorbed water. Another method of modifying the strength or elasticity of hydrogels is to graft or surface coat them onto a stronger/stiffer support, or by making superporous hydrogel (SPH) composites, in which a cross-linkable matrix swelling additive is added. Other additives, such as nanoparticles and microparticles, have been shown to significantly modify the stiffness and gelation temperature of certain hydrogels used in biomedical applications.
Natural hydrogel materials are being investigated for tissue engineering; these materials include agarose, methylcellulose, hyaluronan, Elastin like polypeptides and other naturally derived polymers. Hydrogels show promise for use in agriculture, as they can release agrochemicals including pesticides and phosphate fertiliser slowly, increasing efficiency and reducing runoff, and at the same time improve the water retention of drier soils such as sandy loams.
In the 2000 there has been an increase in research on the use of hydrogels for drug delivery. Polymeric drug delivery systems have overcome challenge due to their biodegradability, biocompatibility and anti-toxicity. Recent advances have fueled the formulation and synthesis of hydrogels that provide strong backbone for efficient component for drug delivery systems. Materials such as collagen, chitosan, cellulose and poly (lactic-co-glycolic acid) all have been implemented extensively for drug delivery to various important organs in the human body such as: the eye, nose, kidneys, lungs, intestines, skin and the brain. Future work is focused on better anti-toxicity of hydrogels, varying assembly techniques for hydrogels making them more biocompatible and the delivery of complex systems such as using hydrogels to deliver therapeutic cells.
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