What is Hydrogel?

Hydrogel is a hydrophilic polymer synthesized from natural or synthetic materials with a three-dimensional network structure. Due to the presence of hydrophilic groups such as -NH₂, -COOH, and -OH, hydrogen bonds can be formed with water molecules inside the hydrogel network, allowing the hydrogel to absorb and retain a large amount of water. Not only are hydrogels highly flexible, but they also have a soft rubbery consistency similar to living tissue, making them ideal raw materials for a variety of applications. Especially in many aspects of the biomedical field, major breakthroughs have been made.

Hydrogel Classification

According to the response of hydrogels to external stimuli, Hydrogels can be divided into traditional hydrogels and environment-sensitive hydrogels. Traditional hydrogels are relatively insensitive to changes in the environment. Sensitive hydrogels can sense small changes or stimuli in the external environment, and produce corresponding changes or even mutations in physical structure and chemical properties. Sensitive hydrogels can be further divided into temperature-sensitive hydrogels, pH-sensitive hydrogels, light-sensitive hydrogels, and pressure-sensitive hydrogels. This kind of hydrogel material has good research and market application prospects due to its different response performance to different environmental conditions.

According to different hydrogel network bonding, hydrogels can also be divided into physical hydrogels and chemical hydrogels. Physical hydrogels are formed by physical forces such as electrostatic interactions, hydrogen bonding, chain entanglement, etc. Chemical hydrogels are three-dimensional network polymers formed by cross-linking chemical bonds.

Fig. 1. Hydrogel network structure (Polym, J. 2010, 42: 839-851).

According to different synthetic materials, hydrogels are further divided into synthetic polymer hydrogels and natural polymer hydrogels. Natural polymer hydrogel includes gelling factors, such as starch, cellulose, alginic acid, collagen and other polysaccharides and polypeptides. Synthetic polymer hydrogel is the gel factor, such as polyacrylic acid, polyethylene glycol, etc. as the main raw materials.

Hydrogel Properties

Functional Carrier Hydrogel

Hydrogels are good functional carriers because of their good hydrophilicity, biocompatibility, and three-dimensional (3D) porous structure similar to extracellular matrix (ECM). Hydrogels can not only load macromolecules such as small-molecule drugs and proteins, but also nanomaterials such as nanovesicles and nanoparticles, making the function of hydrogels change from a single physical coverage or a single function to a multi-functional one. Combination, and showing a trend of further intelligence.

Self-healing Hydrogel

Self-healing hydrogels are widely used in the biomedical field as smart materials that can repair their own functional and structural damage. Chemically self-healing hydrogels that form reconstituted networks through dynamic covalent bonds are currently the way to go.

Tissue-adhesive Hydrogel

In nature, marine mussels can tightly adhere to the surface of foreign objects in seawater by secreting adhesive proteins, thereby forming hard adhesion plaques. The strong adhesive ability of mussels is derived from a catechol-containing amino acid called L-3,4-dihydroxyphenylalanine (L-DOPA), which is present in the adhesion proteins secreted by mussels. Mussel-like hydrogel has excellent tissue adhesion, hemostasis and antibacterial properties, biosafety and plasticity, and is an ideal medical adhesive material.

Injectable Hydrogel

Injectable hydrogels can fill irregular cavities and allow the simultaneous injection of drugs and biologics, making them of great interest for reconstructive surgery, tissue engineering, and drug delivery applications.

Responsive Hydrogel

Responsive hydrogel, also known as smart hydrogel, refers to a class of smart polymer materials in which the gel network undergoes deformation and phase transition under the stimulation of the surrounding environment, and then undergoes swelling-shrinkage or gel-sol transition. Compared with traditional hydrogels, stimuli-responsive hydrogels have space and time sensitivity, and products made with them have multiple, variable, and controllable properties. The use of specific responsive functional groups and the combination of materials and natural polymers are the main methods for endowing gels with stimuli responsiveness.

Preparation of Hydrogels

The preparation of hydrogel materials is mainly divided into three ways: monomer cross-linking polymerization, graft copolymerization and water-soluble polymer cross-linking.

Monomer Cross-Linking Polymerization

Monomer cross-linking polymerization refers to the method of preparing polymer hydrogel materials through free radical homo-polymerization or copolymerization of monomers in the presence of cross-linking agents. During the polymerization reaction, the polymerization kinetics can be controlled by adding or changing initiators, chelating agents, chain transfer agents, etc. The low cross-linking network structure of polymer hydrogel plays a decisive role in the two most critical properties of gel swelling ability and gel elastic modulus. In addition, the properties of polymer hydrogel materials can be regulated by changing important variables such as polymerization method, monomer type and composition, crosslinker structure and type.

Graft Copolymerization

Many polymer hydrogel materials are prepared by graft copolymerization of α-olefin monomers in natural polymers (such as starch, cellulose, etc.) and their derivatives. Free radical-initiated graft copolymerization is one of the most important graft copolymerization methods, and common initiators include ceric ammonium nitrate and composite initiators.

Fig. 2. Example of hydrogel preparation (J. Vis. Exp. 2017, 127: e56253).

Water-soluble Polymer Cross-Linking

Water-soluble polymers such as polyvinyl alcohol (PVA), polyacrylamide (PAM), polyacrylic acid (PAA), poly-N-methylpyrrolidone, and polyamine can be properly cross-linked to obtain polymer hydrogel materials. This method requires that the raw material to be cross-linked must be a water-soluble polymer. The crosslinking agent must be a multifunctional compound or a multivalent metal ion that can react with the functional group of the water-soluble polymer. The key to preparing polymer hydrogel materials from water-soluble polymers is the control of the degree of cross-linking. The chemical reagent cross-linking method mainly relies on the control of the amount of cross-linking agent added, while the key to the radiation cross-linking method is the effective control of the radiation dose.

Applications of Hydrogels in Biomedicine

Hydrogels provide a physiologically similar environment for cell growth, and they are often used to mimic the extracellular matrix (ECM). Therefore, hydrogels have been developed for a variety of biomedical applications, including wound dressings, drug delivery and controlled release, tissue engineering, bone repair, etc.

Hydrogel Wound Dressing

Wound dressings can be divided into dry dressings and wet dressings. Although common dry dressings such as gauze have a protective effect on the wound surface, they are prone to adhesion to the new wound tissue, requiring frequent dressing changes. Wet dressings include hydrogel dressings, hydrocolloid dressings, foam dressings, etc. Hydrogels are considered to be the best candidates for wet dressings due to their high water content, biocompatibility, and similar structure to the macromolecular components of the human body. Because they can provide a moist environment at the wound site, help remove wound exudate, prevent infection, and provide the right environment for tissue regeneration. In addition, hydrogels can reduce the risk of scarring and facilitate the migration of epithelial cells into wounds.

Drug Delivery

Due to the three-dimensional network structure and strong water retention capacity, hydrogels have been widely used to encapsulate and control release therapeutic drugs and proteins. The drug-loaded hydrogel can be used as a drug library for sustained release of drugs at the injury site, which not only achieves effective controlled release of drugs, but also improves the utilization of drugs. Drug delivery can be controlled by diffusion, swelling release mechanisms. In addition, by choosing biodegradable hydrogel materials, the gel controlled release system can even be removed from the body, thereby reducing the damage to the body. For drug delivery applications, these hydrogels may also need to respond to environmental stimuli through changes in their chemical, microscopic or bulk mechanical properties.

Fig. 3. Application of hydrogels in drug delivery (Advanced Drug Delivery Reviews. 2021, 168: 79-98).

Tissue Engineering

The skeleton structure of biomaterials plays an important role in tissue engineering, providing mechanical support and developmental guidance for cell growth and new tissue formation. The superior viscoelasticity of hydrogels and their similar properties to extracellular matrix (ECM) enable them to serve as cell-supporting scaffolds for soft tissue regeneration. In cartilage and bone tissue engineering, collagen hydrogel can be used as an immunomodulatory scaffold to affect cartilage formation; adding fibroblast growth factor to the gel can promote the repair of tympanic membrane; serum protein-rich hydrogel can also promote the repair of intervertebral disc damage; in neural tissue engineering, alginate hydrogels with special swelling and mechanical properties can be used to culture neural tissue in vitro.

Medical Implant Intervention

Hydrogel interventional therapy is a new application of hydrogel in the field of biomedicine. Through the interfacial in situ polymerization technology of hydrogel, a thin layer of hydrogel coating is formed on the inner surface of blood vessels, thereby isolating the contact between blood and injured vessel walls, and inhibiting platelet deposition, thrombus formation and neointima expansion. In addition, the bioactive hydrogel coating can promote the healing of vascular endothelium by introducing bioactive factors, thereby restoring the normal function of blood vessels.

Contact Lenses

Hydrogel systems based on poly(2-hydroxyethyl methacrylate) (PHEMA) were the first hydrogel materials used to manufacture contact lenses. Subsequently, hydrophilic polymers such as polyvinyl alcohol and polyacrylonitrile were investigated for the manufacture of hydrogel contact lenses. In addition, the researchers investigated silicone and fluorine-based hydrogel contact lenses. Silicone-based hydrogel contact lenses are one of the main hydrogel materials today. Soft or hydrogel contact lenses should have high water content, oxygen permeability and ability to transfer water. Long-term use of conventional hydrogel contact lenses can cause corneal physiological hypoxia, affecting corneal integrity and function. The high oxygen permeability of silicon-based soft contact lenses can avoid these adverse effects. But silicon-based hydrogel contact lenses may also affect corneal homeostasis after long-term use.

Electroconductive hydrogels (EHs)

Electroconductive hydrogels (EHs) not only have excellent physical and chemical properties and biocompatibility, but also have the conductivity and multiple stimuli responsiveness of conductive polymer materials. Conductive polymers in EHs can often improve the mechanical properties of hydrogels, making them tougher. EHs can be used as the matrix of cell culture and the framework of tissue culture, and EHs is also applied to the intelligent drug-loading system of drug-controlled release, so that the drug can be released at a timed and fixed point. Because EHs can respond to multiple stimuli and convert them into electrical signals, they can be used as the core components of chemical sensors and biosensors. Combining the two advantages of controlled drug release and biosensing, soft conductive hydrogel devices can be implanted into the human body to perform functions such as real-time monitoring and treatment. EHs can also be made into smart electronic devices and worn on the surface of the human body.

PEG Hydrogel

PEG hydrogels are formed by cross-linking polyethylene glycol chains to form a stable porous network structure. Crosslinking can be achieved by various methods, such as chemical reactions or physical interactions. The degree of crosslinking can be tuned to control the properties of the hydrogel, including its mechanical strength, porosity, and swelling behavior. PEG hydrogels have several unique properties that allow them to be used in a variety of applications. Their high water content mimics the natural environment of many living tissues and allows efficient diffusion of nutrients and waste. They are also biocompatible, meaning they are generally well tolerated by organisms and do not cause significant immune responses or toxicity.

BOC Sciences offers PEG hydrogel solutions in different forms, including pre-polymerized hydrogel solutions and hydrogel precursors for in situ gelation. Our PEG hydrogels can be customized with different molecular weights, cross-linking densities, and functional groups to meet the multifunctional needs of cell culture, tissue engineering, drug delivery, and other biomedical applications. In addition, BOC Sciences offers a comprehensive PEG product catalog including different molecular weights, functional groups, and chemical modifications. We can supply PEGs with molecular weights ranging from a few hundred Daltons to several thousand Daltons. These PEGs can be customized with various functional groups such as amino PEG, carboxylic acid PEG, thiol PEG, etc. to meet specific requirements.

References

1. Imran, A. et al. Recent advances in hydrogels in terms of fast stimuli responsiveness and superior mechanical performance. Polym, J. 2010, 42: 839-851.
2. Li, Y. et al. Preparation of Chitosan-based Injectable Hydrogels and Its Application in 3D Cell Culture. J. Vis. Exp. 2017, 127: e56253.
3. Mo, F. et al. DNA hydrogel-based gene editing and drug delivery systems. Advanced Drug Delivery Reviews. 2021, 168: 79-98.