Perspective Chapter: Introduction to Hydrogels – Definition, Classifications, Applications and Methods of Preparation

Abstract

Hydrogel products are a group of polymeric materials that possess a hydrophilic structure, allowing them to retain significant amounts of water within their three-dimensional networks. The development of new materials is crucial for advancing technologies, and this often involves the innovative combination of existing components. A combination that incorporates both a polymer hydrogel network and nanoparticles can be achieved by combining metals, non-metals, metal oxides, and polymeric moieties. The composite material’s functionality will be enhanced by this amalgamation, which has applications in various fields such as catalysis, electronics, biosensing, drug delivery, nano-medicine, and environmental remediation. The incorporation of nanoparticles into hydrogels can result in synergistic property enhancements, such as improved mechanical strength of the hydrogel and a reduction in nanoparticle aggregation. These mutually beneficial effects have attracted significant interest from multidisciplinary research groups over the past decade. In this chapter, we delve into recent advancements in nanoparticle-hydrogel composites, focusing on their synthesis, design, potential applications, and the inherent challenges associated with these exciting materials.

1. Introduction

Hydrogels are unique materials that consist of a three-dimensional network of hydrophilic polymers. They can absorb and retain large amounts of water or aqueous fluids without completely dissolving. The water-retaining capacity of hydrogels is attributed to the functional groups attached to the polymer backbone, such as hydroxylic, amidic, carboxylic, sulfonic, and primary amidic groups. These groups have a high affinity for water. The cross-links between the polymer chains provide structural integrity to the hydrogel and prevent its disintegration. Hydrogels can exhibit softness, high efficiency, and the ability to store materials, making them versatile materials for various applications. Hydrogels also act as matrices that allow the diffusion of certain solute molecules while holding water together. They form semi-open macromolecular network systems with intertwined or cross-linked chains of different lengths. When exposed to a compatible solvent like water or biological fluids, hydrogels swell and trap a large amount of solvent molecules within their pores. Hydrogels can undergo phase transitions, including gel-sol transitions, in response to physical or chemical stimuli. Physical stimuli such as temperature, pressure, magnetic and electric fields, light intensity, and solvent compositions can trigger these transitions. Chemical or biochemical stimuli include ions, pH changes, and specific chemical compositions. The response of hydrogels to external stimuli depends on factors such as charge density, degree of cross-linkage, presence of free chains, and the nature of the monomer used.

The synthesis of hydrogels involves a series of chemical events, including polymerization and cross-linking of multifunctional monomers. One method is the reaction between polymers and cross-linking agents. Another approach is a multistep process where a polymer with reactive groups is synthesized first, followed by cross-linking with suitable agents. These reactions can involve various chemical interactions, such as ionic forces, hydrogen bonds, van der Waals interactions, primary covalent cross-linkages, affinity interactions, and hydrophobic interactions. These interactions contribute to holding the molecules within the three-dimensional matrix of the hydrogel. Hydrogels can be synthesized from both natural and synthetic polymers. Natural polymers such as agarose, alginate, collagen, chitosan, chondroitin sulfate, dextran, fibrin, gelatin, hyaluronic acid, and pectin can be used. Synthetic polymers include polyacrylic acid, polyacrylamide, polyvinyl alcohol, polyethylene oxide, polyhydroxyethyl methacrylate, poly-2-hydroxyethyl methacrylate (PHEMA), polypropylene fumarate-co-ethylene glycol, polypeptides, and poly(N-isopropylacrylamide). In many hydrogel formulations, a combination of natural and synthetic polymers is used to enhance the physicochemical properties and biocompatibility. This can be achieved through interpenetrating polymer networks (IPN) or semi-interpenetrating polymer networks (semi-IPN).

According to the findings of Javad Alaei et al. [1], the industrial production of hydrogels encompasses solution polymerization, reversed suspension polymerization, and reversed emulsion polymerization techniques. Figure 1 presents a schematic diagram illustrating the key steps involved in the manufacturing of hydrogels at semi-pilot and industrial scales.

Figure 1.

Hydrogel preparation block diagram (solution polymerization/cross-linking procedure).

The use of classical organic reactions between the functional groups of the polymer being utilized is common for cross-linking polymeric materials. The Huisgen cycloaddition, the Diels-Alder reaction, the Michael addition, and the Schiff base reaction are just a few of the reactions that are notable (Figure 2) [2].

Figure 2.

Schematic overview of the different cross-linking methods for preparing hydrogels.

Indeed, hydrogels have gained significant attention in recent years due to their unique characteristics and versatile properties. They find applications in various industries, particularly in the biomedical field. Here are some key areas where hydrogels are extensively used: biomedical engineering, 3D printing, agriculture, food packaging, separation technology, cosmetics and personal care, biosensors, and bio-microelectromechanical systems (Bio-MEMS). The unique characteristics of hydrogels, including their biocompatibility, water retention capacity, and tunable properties, make them highly attractive for a wide range of applications across multiple industries. Ongoing research and development in the field of hydrogels continues to expand their potential applications and impact.

2. History of hydrogels

Bacterial biofilms and plant structures have long been observed as water-swollen motifs in nature. Throughout human history, gelatin and agar were discovered and utilized for various purposes. However, the specific history of hydrogels as a distinct group of materials designed for biological applications can be traced back to more recent times. The term “hydrogel” was coined by Lee, Kwon, and Park in 1894. However, the substance they described was not a hydrogel in the modern sense but rather an inorganic salt-based gel. Despite this, the term “hydrogel” has endured and continues to be used to describe a wide range of water-swollen materials. In the nineteenth century, Thomas Graham conducted the first scientific study of gels. He produced a silica gel using sol–gel chemistry, laying the groundwork for the understanding of gel formation. In 1974, Paul Flory was awarded the Nobel Prize in Chemistry for his contributions to polymer science, including the development of macromolecules and polymers. His work played a pivotal role in advancing the field of polymer science. Another notable figure in the history of polymers is Alan G. Wardhaugh Treloar, who made significant contributions to the study of polymer elasticity. His work greatly influenced the understanding of polymer behavior and properties. The combined efforts of these pioneers and many others have shaped the field of hydrogels and polymer science as we know it today. Their research and discoveries have paved the way for the development and application of hydrogels in various fields, including biomedicine, materials science, and engineering [3, 4].

Hydrogels have indeed played a significant role in biomedical applications and have been used with human tissues as biocompatible materials. The development of the first synthetic hydrogel based on poly-2-hydroxyethyl methacrylate (PHEMA) for contact lens applications was described by Wichterle and Lim [5]. This breakthrough led to the use of PHEMA hydrogels as contact lenses, marking one of the early successful applications of hydrogels in 1960. This development paved the way for the emergence of biomedical hydrogels, which are specifically designed for applications within the human body. Since the 1970s, numerous studies have been conducted to explore the diverse biomedical applications of hydrogels. In the 1980s, countries like Germany and France started incorporating hydrogels into diaper products, which further propelled advancements in the field of hydrogel research. As interest in biopolymers and hydrogels grew, more researchers began focusing on developing efficient and biocompatible hydrogels. This involved studying the properties and characteristics of hydrogel and polymer materials in-depth. The goal was to enhance the functionality, biocompatibility, and performance of hydrogels for various biomedical applications. Over time, advancements in materials science, polymer chemistry, and fabrication techniques have led to the development of a wide range of hydrogels with tailored properties. These hydrogels can now be designed to possess desired characteristics such as mechanical strength, controlled drug release, stimuli-responsiveness, and biodegradability, making them suitable for applications in tissue engineering, drug delivery, wound healing, and other biomedical fields. The continuous exploration and research in the field of hydrogels have contributed to the development of more efficient and versatile materials with enhanced biocompatibility, expanding the potential applications and impact of hydrogels in the biomedical domain.

There are three generations of hydrogel development: first, second, and third [6]. To obtain hydrogels with desirable swelling, physicochemical, and mechanical properties, first-generation hydrogels employ diverse cross-linking methods and modifications of monomers or polymers.

Second-generation hydrogels emerged in the mid-1970s, with a focus on incorporating responsive behavior to environmental stimuli. These hydrogels can respond to stimuli such as temperature, pH, solvent composition, molecule concentration, and ionic charge changes. Their responsive nature finds applications in drug delivery, in situ pore formation, polymerization, and cross-linking.

The current research is directed toward developing third-generation hydrogels, often referred to as smart hydrogels. These advanced hydrogels exhibit dynamic properties and can change their composition and texture in response to external stimuli like temperature, pH, solvent composition, and electric fields. They are considered smart materials and are being explored for a wide range of applications.

Over the past 50 years, hydrogels have found extensive applications in various sectors, including agriculture, biomaterials, pharmaceutics, biotechnology, and wastewater treatment. In recent years, hydrogels have made significant breakthroughs in tissue engineering, enabling advancements in wound healing, tissue repair, and regenerative medicine. The use of hydrogels in tissue engineering gained momentum with Lim and Sun’s work in 1980, demonstrating the feasibility of using calcium alginate microcapsules for cell encapsulation. Yannas and colleagues made significant progress in the field in the 1980s by creating hydrogels made from natural polymers like collagen and shark cartilage to be used as artificial burn dressings. Hydrogels that are composed of natural and synthetic polymers have become popular for encapsulating cells and have been utilized in tissue engineering for healing and regenerating various tissues and organs. The field of hydrogels is continuously evolving, and the development of smart hydrogels with adjustable characteristics and responsive behavior opens up vast possibilities in engineering and medical applications. The potential for further advancements and applications in this field appears to be limitless [7].

3. Classifications of hydrogels

Hydrogels can be categorized based on various characteristics and factors (Figure 3) [8, 9]. Some common classification criteria include:

1. Physical Characteristics: Hydrogels can be classified based on physical mechanisms that contribute to their structure and properties, such as hydrophobic association, chain aggregation, crystallization, polymer chain conformation, and hydrogen bonding.

2. Swelling Characteristics: Hydrogels can be classified based on their swelling behavior, including the extent of swelling, response to stimuli, and the ability to retain or release water or other substances.

3. Manufacturing Process: Hydrogels can be classified based on the method of fabrication, such as physical gelation, chemical cross-linking, or a combination of both.

4. Origin or Source: Hydrogels can be classified based on their origin, distinguishing between natural hydrogels derived from biological sources (e.g., proteins, polysaccharides) and synthetic hydrogels produced from synthetic polymers.

5. Ionic Charge: Hydrogels can be classified based on their ionic charge, which can be positively charged (cationic), negatively charged (anionic), or neutral.

6. Biodegradation Rate: Hydrogels can be categorized based on their rate of biodegradation, distinguishing between fast-degrading hydrogels that break down relatively quickly and slow-degrading hydrogels that maintain their structure for a longer duration.

7. Cross-Linking: Hydrogels can be classified based on the type of cross-linking present, such as physical cross-linking (reversible interactions) or chemical cross-linking (covalent bonds). Chemical hydrogels have permanent and irreversible cross-linking, while physical hydrogels exhibit reversible conformational changes.

Figure 3.

Hydrogel classification: A diagrammatic depiction.

Additionally, dual-network hydrogels are a type of hydrogel that combines both physical and chemical cross-linking, enabling electrostatic interactions between the networks. This type of hydrogel overcomes some limitations associated with using solely physical or chemical hydrogels, providing high liquid absorption capacity over a wide pH range and increased sensitivity to pH changes compared to chemical hydrogels. Hydrogels can have diverse compositions and properties, and their classification can be based on a combination of factors such as physical condition, polymeric composition, pore size, physical appearance, and configuration. This classification helps in understanding and categorizing the wide range of hydrogel types available in both natural and synthetic forms.

3.1 Classification based on origin

Hydrogels can be classified into three main types based on their composition: natural hydrogels, synthetic hydrogels, and hybrid hydrogels:

1. Natural Hydrogels: These hydrogels are derived from natural polymers, such as polysaccharides and proteins. Examples of natural hydrogels include agarose, chitin, hyaluronic acid (HA), collagen, dextran, and gelatin. Natural hydrogels are biocompatible, biodegradable, and often possess high cell adhesion properties. They are synthesized from naturally occurring biomaterials and find applications in various biomedical fields.

2. Synthetic Hydrogels: Synthetic hydrogels are created through polymerization processes using artificial monomers. They are engineered materials with a wide range of chemical and mechanical properties. Examples of synthetic hydrogels include polyethylene glycol (PEG)-polylactic acid (PLA) hydrogels. Synthetic hydrogels are more inert compared to natural hydrogels and offer advantages such as high compatibility, low immunogenicity, and nontoxicity. They are commonly used in biomedical applications due to their controlled and tailored properties.

3. Hybrid Hydrogels: Hybrid hydrogels are a combination of natural hydrogels and synthetic polymer hydrogels. These hydrogels are designed to leverage the benefits of both natural and synthetic components. Natural polymers like chitosan, collagen, and dextran are mixed with artificial polymers such as polyvinyl alcohol and poly(N-isopropylacrylamide) to create hybrid hydrogels. By combining different materials, hybrid hydrogels can exhibit enhanced properties and functionalities, making them suitable for various biomedical applications.

The classification of hydrogels into natural, synthetic, and hybrid types allows researchers and engineers to choose the most appropriate hydrogel materials based on their specific requirements and desired properties.

3.2 Classification based on polymeric composition

Hydrogels can be further classified into different types based on the composition and structure of their polymer networks. Some of these types include:

1. Homopolymer Hydrogels: Homopolymeric hydrogels are cross-linked polymer networks formed from a single type of monomer. The choice of monomer, polymerization method, and cross-linker influences the structural composition of these hydrogels. For example, polyethylene glycol (PEG) homopolymer hydrogels are often used for controlled release applications in drug delivery systems due to their biocompatibility and ability to control the release of medicines, proteins, and biomolecules.

2. Copolymer Hydrogels: Copolymeric hydrogels consist of two or more types of monomer species in their polymeric network. Typically, one of the monomers is hydrophilic, enabling the hydrogel to swell. Copolymer hydrogels can have various arrangements of monomers, including graft, random, block, and alternate configurations. The hydrogels are formed by polymerizing or cross-linking two monomers using a single initiator and cross-linker. The physical cross-linking in copolymer hydrogels can occur through interactions such as hydrogen bonding, chain aggregation, ion-polymer complexation, and ionic interactions. Examples of copolymer hydrogels include carboxymethyl cellulose and carboxymethyl chitosan-based hydrogels used for metal ion adsorption.

3. Multipolymer Hydrogels: Multipolymer hydrogels are formed from three or more monomers through polymerization and cross-linking reactions. The independent polymer components can be of synthetic or natural origin and are cross-linked together to form a network. An example of a multipolymer hydrogel is poly (acrylic acid-2-hydroxy ethyl methacrylate) or gelatin hydrogel.

4. Interpenetrating Network (IPN): Interpenetrating network hydrogels consist of two interlaced polymer networks without chemical interactions between them. The first polymer network is linear, while the second polymer network is cross-linked. The linear network of the first polymer diffuses into the second polymer, resulting in interlocking and strong cross-linking between the two networks. IPN hydrogels can overcome thermodynamic incompatibility and restricted phase separation. Semi-interpenetrating networks (Semi-IPN) are a type of IPN where the linear polymers are scattered inside the first network. IPN hydrogels can be synthesized through simultaneous or sequential methods.

In summary, hydrogels can be classified into various types based on their composition and structure, including homopolymer hydrogels, copolymer hydrogels, multipolymer hydrogels, and interpenetrating network (IPN) hydrogels. These classifications help in understanding the different types of hydrogels and their applications in various fields, such as drug delivery, tissue engineering, and biomaterials.

3.3 Classification based on ionic charge

Hydrogels can also be classified based on the electric charge on their cross-linked chains. Here are the three types:

1. Neutral (Nonionic) Hydrogels: Neutral hydrogels have no net charge on their side groups or backbone. They do not contain any ionizable groups. These hydrogels are electrically neutral and do not exhibit specific interactions with ions or charged molecules. They are typically used in applications where a neutral environment is desired, such as in contact lenses.

2. Ionic Hydrogels: Ionic hydrogels contain ionizable groups that can be either cationic or anionic. These groups introduce a net positive or negative charge to the hydrogel. Cationic hydrogels have positively charged groups, such as amines, while anionic hydrogels have negatively charged groups, such as carboxylic acids or sulfonic acids. The swelling properties of ionic hydrogels can be pH-dependent. Cationic hydrogels tend to swell more at lower pH values, while anionic hydrogels show increased swelling at higher pH values.

3. Ampholytic (Amphoteric) Hydrogels: Ampholytic hydrogels contain both negative (basic) and positive (acidic) charges on the same polymer chain. These charges can coexist and are balanced at the isoelectric point. Ampholytic hydrogels can exhibit different properties depending on the pH of the surrounding environment. They can respond to changes in pH by altering their swelling behavior or charge distribution. These hydrogels find applications in pH-sensitive drug delivery systems and biomaterials.

Additionally, there is a category known as zwitterionic hydrogels, where each structural unit contains both anionic and cationic groups. This balanced charge distribution provides unique properties to zwitterionic hydrogels, such as excellent biocompatibility, low fouling, and resistance to protein adsorption. Zwitterionic hydrogels have gained attention for applications in biomedicine, such as coatings for medical devices and tissue engineering scaffolds. The classification of hydrogels based on electric charge helps in understanding their behavior and properties in different environments, and it enables the design of hydrogels with specific functionalities for various applications.

3.4 Classification based on configuration

Hydrogels can also be classified based on their structural organization, specifically regarding the presence or absence of crystalline regions. Here are the three types:

1. Amorphous (Noncrystalline) Hydrogels: Amorphous hydrogels have randomly arranged macromolecular chains in their polymeric networks. They lack a well-defined crystalline structure. The absence of crystalline regions gives amorphous hydrogels a more flexible and disordered nature.

2. Semicrystalline Hydrogels: Semicrystalline hydrogels exhibit a complex blend of amorphous and crystalline phases. In these hydrogels, there are sections or domains where the macromolecular chains are organized into a more ordered, crystalline structure. These crystalline regions coexist with the amorphous regions, resulting in a combination of mechanical properties associated with both structures.

3. Crystalline Hydrogels: Crystalline hydrogels consist primarily of a well-defined crystalline phase. The macromolecular chains within the hydrogel are highly organized and aligned in a repeating, three-dimensional lattice structure. These hydrogels have distinct crystalline regions and exhibit unique mechanical, thermal, and chemical properties associated with crystallinity.

The structural organization of hydrogels, whether they are amorphous, semicrystalline, or crystalline, can significantly affect their mechanical strength, swelling behavior, and other properties. The type of structural organization desired in a hydrogel depends on the specific application and the desired properties required for that application.

3.5 Classification based on cross-linking

Hydrogels can be classified into two types based on the nature of cross-linking: physical hydrogels and chemical hydrogels.

1. Physical Hydrogels: Physical hydrogels are cross-linked through reversible physical interactions rather than covalent chemical bonds. These physical interactions can include crystallization, hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Physical hydrogels can undergo reversible changes in their structure and properties in response to external stimuli, such as temperature, pH, or solvent composition. These hydrogels can exhibit tunable gelation and sol–gel transitions, making them suitable for applications such as drug delivery, tissue engineering, and sensors.

2. Chemical Hydrogels: Chemical hydrogels are cross-linked through covalent chemical bonds, resulting in the formation of permanent junctions within the polymer network. The cross-linking can occur through various chemical reactions, such as polymerization, condensation, or click chemistry reactions. Chemical hydrogels have stable and permanent cross-links, providing them with robust mechanical properties and resistance to changes in environmental conditions. These hydrogels are commonly used in applications requiring long-term stability and structural integrity, such as biomedical implants, wound dressings, and scaffolds for tissue engineering.

The classification of hydrogels into physical and chemical types is based on the underlying cross-linking mechanism. This classification is essential for understanding the behavior and properties of hydrogels and selecting the appropriate type for specific applications.

4. Applications of hydrogel

In the past few decades, hydrogels due to their unique properties including abundance, cheapness, renewableness, non-toxicity, biodegradability, and biocompatibility have been used in various industries such as food, packaging, pharmaceuticals, agriculture, biomedical and bioengineering applications, in the construction of technical and electronic devices, also as absorbents to remove pollutants in environmental applications, and in ionic liquids. Considering the importance and diverse capabilities of these compounds as promising materials in various applications, in this section, their important applications in various fields have been reviewed.

4.1 Food packaging

The hydrogel is comprised of a complex network structure made up of polymeric chains, creating a porous, three-dimensional (3D) network. The formation of such a structure is achieved by cross-linking polymer chains of natural or synthetic polymers that have the capability to absorb and retain a significant amount of water in their interstitial frameworks (Figure 4).

Figure 4.

Structural chemistry of a hydrogel: (a) the structure of a hydrogel at the molecular level is the subject of structural chemistry. (b) the relationship between the swelling ratio of the hydrogel and osmotic pressure and elastic stress.

In recent years, the use of sustainable packaging resources in the circular economy framework has gained considerable attention as a way to decrease waste and decrease the negative environmental impact of packaging materials. Bio-based hydrogels are being examined for their potential applications in various fields, including food packaging, in line with these trends. The hydrophilic nature of hydrogels is a promising solution for food packaging systems, especially in controlling moisture levels and transporting bioactive substances, which can significantly impact the shelf life of food products. In general, the creation of cellulose-based hydrogels (CBHs) and their offshoots has resulted in hydrogels that are appealing due to their flexibility, water absorption, swelling capacity, biocompatibility, biodegradability, stimulus sensitivity, and cost-effectiveness. The purpose of this review is to provide an overview of the latest trends and applications of CBHs in the food packaging industry, with a focus on CBH sources, processing methods, and cross-linking methods used to create hydrogels through physical, chemical, and polymerization processes [10]. Chitosan (CH), which is the only natural cationic polysaccharide, has multiple bioactive properties. Moreover, chitosan was the ideal biomaterial for preparing hydrogels due to its desirable biocompatibility and biodegradability. CH-based hydrogels have been extensively studied for their applications in delivery systems and tissue engineering. Additionally, they have shown great potential and garnered considerable attention in recent years for use in biosensors and packaging materials [11]. Sugarcane bagasse’s nanocellulose has been used to develop a hydrogel that can be used as a colorimetric indicator for monitoring the freshness of chicken breasts. The preparation of nanocellulose from sugarcane bagasse cellulose filaments was done through TEMPO-mediated oxidation, and then it was utilized to create a resilient hydrogel matrix by cross-linking with Zn²⁺ [12]. This review examines the current status of natural hydrogels for sustainable food packaging. The hydrogels are based on proteins, polysaccharides, lipids, and other biodegradable polymers. The review also focuses on the functionalization of these hydrogels with bioactive compounds, particularly phenolic compounds. Incorporating them into the hydrogel’s formulation appears to enhance the mechanical, antioxidant, and antimicrobial properties of the resulting films, as well as extend the shelf life of food products. This review compiles recent applications of natural hydrogels in food. Although current research is still in its early stages, the results obtained thus far are promising. This represents an innovative, sustainable alternative to plastic materials for extending the shelf life of food products [13].

4.2 Pharmaceuticals

The versatility and potential demand of hydrogels can be attributed to their ability to absorb large amounts of aqueous solutions without losing shape or mechanical properties, as well as their ability to load drugs of different types, including hydrophobic and biomolecules. Many pathways of synthesis have been developed, particularly for chemical/permanent hydrogels, as they have been explored in numerous studies for years. The regulation of properties such as targeting and drug release can be enhanced by using stimuli-responsive hydrogels, also known as intelligent materials, which have been investigated. The control of particle size has led to similar studies of hydrogels on the micro- and nanoscale, which have increased the possibilities for applications of so-called XXI century materials even more. Our objective was to provide an overview of recent studies on the synthesis, biomedical, and pharmaceutical applications of macro-, micro-, and nanogels. The size of the particles obtained can determine the classification of hydrogels as macro-, micro-, or nanogels. When they are smaller than 100 nm, they are usually considered nanogels, while gels with particle sizes bigger than this (up to the micrometer range) are called microgels. Finally, if these gels have particle sizes bigger than 100 μm, they are usually called macrogels (Figure 5) [14]. Cellulose and lignin are natural, abundant, biodegradable, and environmentally friendly polymers. In addition, the presence of reactive functional groups and the ability to chemically modify cellulose and lignin provide great potential for development of products for the medical sciences and pharmaceuticals. Hydrogels in drug delivery systems have potential to give better performance of drugs. The properties of hydrogels and their constituent polymers are among the most challenging issues in this field. Research has shown that biopolymers, mainly cellulose and lignin, are excellent components for drug delivery hydrogels. These two biopolymers and their derivatives can be used as matrix hydrogels and cross-linking agents, improving mechanical properties and designing an engineered function for hydrogels, including their usage as pharmaceutical agents. The use of cellulose and lignin, their chemical interactions in producing hydrogels, and the applications and properties that make these two polymers so vital. Various applications can benefit from the incorporation of cellulose or lignin structures into hydrogels to develop unique or exceptional characteristics [15].

Figure 5.

Representative scheme of gels at different size levels.

4.3 Agriculture

Controlling the release of macronutrients in hydrogels can be achieved by using biopolymers, which are a solution for agricultural production. To synthesize SAH, graft copolymerization of babassu mesocarp (MB) and polyacrylamide (PAM) was necessary. The characterization of these materials was done using X-ray diffraction (XRD). Differences in crystallographic characteristics between hydrogels and their precursors suggested interactions between fertilizers and macromolecular chains. FTIR revealed a band at 1121 cm⁻¹ that distinguishes HMBP and HMB hydrogels and was attributed to the inclusion of potassium phosphate. The obtained materials were found to be thermally stable through thermo-gravimetric analysis (TG and DTG) [16]. The use of superabsorbent polymer hydrogels in agriculture has been presented as materials to store and retain water and nutrients and as additives to improve soil properties. The use of synthetic and natural polymer hydrogels for these purposes is considered. Although natural polymers, such as various polysaccharides, have undoubted advantages in terms of biocompatibility, biodegradability, and low cost, they are inferior to synthetic polymers in terms of water absorption and retention. The most promising in this respect are semi-synthetic polymeric superabsorbents based on natural polymers modified with additives or grafted chains of synthetic polymers, which can combine the advantages of natural and synthetic polymeric hydrogels without their disadvantages. Such semi-synthetic polymers are of great interest for agricultural applications, especially in arid regions, also because they can be used to create systems for the slow release of nutrients into the soil, which is necessary to increase crop yields using environmentally friendly technologies. One of the most pressing problems in agriculture is the shortage of water for irrigation. Superabsorbent polymers (SAPs) are widely used as containers for water and plant nutrients, especially in arid and semi-arid regions, because they significantly improve the efficiency of water use. A recent review found that applying 100 kg of SAP per hectare is the most suitable rate for increasing seed and dry matter yields while taking economic considerations into account, and it can result in a cereal seed yield increase of more than 15%. Cross-linked polymer networks that contain water-soluble building blocks are what SAPs are referred to as. Our review will categorize superabsorbent polymers or polymer hydrogels into synthetic, natural, and semi-synthetic based on their chemical structure [17]. In this review, superabsorbent polymers or polymer hydrogels have been classified according to their chemical structure as synthetic, natural, and semi-synthetic. The addition of external cross-linking molecules can lead to covalent bonding. In an aqueous environment, the dissolution of hydrophilic polymer chains can be prevented by using crosslinkers in a hydrogel preparation. Crosslinkers that are added to polymer chains can affect the physical properties of the polymer and the presence or absence of crystallinity. Cross-linking causes changes in the chemical structure of the polymer. The formation of bridges between polymer chains is possible due to the presence of at least two reactive functional groups in cross-linking molecules (Figure 6). Various synthetic cross-linking compounds such as dialdehydes (glyoxal, glutaraldehyde), epoxy compounds (epichlorohydrin), carbodiimides (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide together with N-hydroxysuccinimide; EDC-NHS), and dithiols can be used for covalent cross-linking. These cross-linker molecules can be attached to polymers that have functional groups such as primary amines, alcohols, thiols, carbonyls, and carboxylic acids through covalent bonding. The Schiff base reaction allows dialdehyde crosslinkers to bind primary amines, leading to the formation of two imine bonds. NH₂-containing polysaccharides and proteins are transformed into hydrogels by the use of dialdehydes. Glyoxal dialdehyde is capable of reacting with the polysaccharide chitosan, for instance. Glutaraldehyde is regarded as one of the most efficient dialdehydes, forming stable cross-links quickly [18].

Figure 6.

A general cross-linking mechanism between nanoparticles and polymeric chains.

4.4 Biomedical

Advanced hydrogels can be classified as static, dynamic, multi-stage, or bioinspired. They can be used as cell-free gene expression platforms for gene therapy. Administration of nanogel-based sprays can act as an immunoassay for priming macrophage toward the M1 phenotype to prevent cancer recurrence after surgery. Nanogels can also serve as a dual biosensing and capture platform for liquid biopsies and can detect and remove circulating cancer cells from the blood of cancer patients. The ATRP technique was utilized to synthesize poly(2-hydroxyethyl methacrylate) (PHEMA)-cross-linked nanogels, which were then investigated as engineered tissue scaffolds that are biodegradable and can be cleaved by enzymes. An ABC triblock polymer (PPS-b-PDMA-b-PNIPAAM) with a reactive oxygen species (ROS)-triggered degradable response was synthesized using a combination of anionic and RAFT polymerization [19]. Collagen-based hydrogels have been the subject of a growing number of investigations, with the aim of overcoming the low mechanical properties of collagen. The biocompatibility of the collagen-alginate composite (CAC) hydrogel is widely appreciated because it gels easily under mild conditions, has low cytotoxicity, has adjustable mechanical properties, is widely available, and can be easily integrated with other biomaterials and bioactive agents. This review is designed to summarize the properties of alginate and collagen. Furthermore, the utilization of CAC hydrogel in tissue engineering and biomedical sciences is also covered [20]. A cross-linked polymer chain with a three-dimensional (3D) network structure is what hydrogels are made of. Hydrogen bonding can lead to the formation of hydrogels by the polymer with functional groups. The formation of amphiphilic grafting and block polymers can be achieved by polymers self-assembling in hydrophobic or hydrophilic solvents because of their amphiphilic affinity. The polymer chains can synthesize hydrogels by adjusting their crystallization temperature through crystallization. Crystallization is commonly achieved through the use of the freeze-thaw and heating processes. During cross-linking, the attraction of ionic groups causes ionic interactions to occur. Proteins and polymers interact when they are added or modified using molecular medical technology, such as protein and genetic engineering. The destruction of complementary RNA strands is a result of the destruction of these small molecules, which reduces protein expression. Improving heart function and repair after myocardial infarction can be achieved through the use of miRNAs, but it requires efficient and sustained delivery to the myocardium. The use of hydrogel nanoparticles as delivery vehicles resulted in miRNA being delivered to the heart. Polymeric nanoparticles embedded in hydrogels contained miRNAs after they were loaded. MiRNA’s localized and sustained release led to cardiomyocyte proliferation, which was triggered by miRNA’s silencing of target proteins. The improvement of cardiac function resulted in an increase in ejection fraction, a reduction in scar size, and a double increase in capillary density in the border zone. Myocardial repair was safely and efficiently accomplished by utilizing the miRNA-loaded hydrogel nanoparticle complex (Figure 7) [21].

Figure 7.

Hydrogels for nucleic acid delivery. Adhesive hydrogel-loaded miRNA nanoparticles promote local immunomodulation for wound healing.

4.5 Adsorbents

The most significant environmental issues worldwide involve the presence of contaminated water and the lack of clean water. The elimination of hazardous organic/inorganic contaminants from water/sewage is crucial to protect clean water resources. Bio-based hydrogels that have luminescent properties such as three-dimensional (3D) microstructures, high porosity, surface area, and multifunctionality can be developed to meet the rising demands of wastewater treatment on an industrial scale. Advanced bio-based hydrogels can be developed to overcome separation problems and advance technological aspects, as described. A brief overview of each treatment technique is described as follows: (i) advanced oxidation, (ii) electrochemical method, (iii) ion exchange, (iv) biodegradation, (v) membrane filtration, (vi) flocculation/coagulation, (vii) irradiation, (viii) solar desalination, (ix) portable water filter [22]. Two cross-linked networks intertwined with balanced mechanical performance form a double-network (DN) hydrogel that has high strength and toughness. In addition to the excellent mechanical properties provided by the double-network structure, it can also have good anti-swelling and self-healing properties, which provide a good basis for the application of hydrogels in the environment. Recently, research on the environmental application of double-network hydrogels has been gradually increasing. We classify this type of hydrogel in terms of composition and cross-linking methods and discuss its adsorption mechanism for various environmental pollutants (metal ions, dyes, antibiotics). This type of hydrogel is classified in terms of composition and cross-linking methods, and its adsorption mechanism for different environmental pollutants (metal ions, dyes, and antibiotics) is discussed [23]. Polymer hydrogels have been developed in different ways to remove hazardous pollutants over the last few decades. The effectiveness of hydrogel adsorbents is determined by the gel’s composition and the functions created by their polymer networks. Over the last decade, research on hydrogels that utilize the characteristic functions of polymer networks has increased. The removal of hazardous pollutants has been facilitated by the development of various adsorption functions of polymer hydrogels over the past few decades. Some adsorbents contain a local gel phase. An adsorbent that has a gel phase throughout is typically identified as a gel adsorbent. The use of polymeric hydrogels as adsorbents has several advantages. Percolation pores with the desired solvent content and pore size can be achieved through the creation of polymer networks. The network structure with a large amount of solvent makes it difficult to discuss the specific surface area of polymer hydrogels. Adsorbents can rapidly penetrate deep into the gels due to the open pores caused by the polymer networks, which enhances their sorption capacity. Gels that contain a lot of solvent have excellent diffusional permeability for a range of substances. Both experimental and theoretical studies have been conducted on the diffusivity of solutes in gels. By developing porous structures in polymeric gels, it is possible to increase the number of effective adsorption sites and decrease the resistance to mass transfer. Porous hydrogels can be synthesized using various methods, such as phase separation, emulsion, ice crystal, and foam. A solution environment that is different from the external solution can be created inside the gels due to the polymer’s nature, which involves the hydrophilic-hydrophobic balance of the polymers and the presence of fixed charges. Polymer gels have been categorized as adsorbents based on their roles and functions [24]. Hydrogels are remarkably able to absorb both water and biological fluids because they are three-dimensional cross-linked stable, networks that are insoluble in water. Natural or synthetic polymers and monomers have been used to synthesize hydrogels, which have made significant progress in many different applications. The backbone of the polymer chain can be grafted with hydrophilic groups like hydroxyl (-OH), carboxylic acid (-COOH), imide (-CONH-), sulfonic acid (-SO₃H), amine (-NH₂), and amide (-CONH₂), and additives can also be added to create composite hydrogel. Different properties like pH, temperature, or light can stimulate polymeric composite hydrogels, which can affect swelling, mechanical properties, and self-healing, which are crucial in various fields. The creation of polymer-based composite hydrogels has been made possible by utilizing physical or chemical cross-linking techniques to enhance their physicochemical, biological, and other properties. The current focus of many researchers is on hydrogels and their applications, which include wastewater treatment and purification, medical and biomedical applications, agricultural applications, and many other industrial applications. The purpose of this review is to sum up the classification of composite hydrogels by their chemical and physical cross-linking techniques, as well as the various polymers and additives used to make them. Hydrogels have an impact on health and the environment, which is also discussed. The production and application of hydrogels have also been discussed and presented with other important issues. A hydrogel is created from a polymer substrate by using hydrophilic monomers that form double bonds during polymerization. Polymeric hydrogels can be made up of either natural or synthetic polymers, or a mixture of both. The hydrogel’s mechanical, salt tolerance, and water retention properties vary depending on the monomer type. The majority of inorganic-organic DN hydrogel components consist of graphene oxide (GO) and natural minerals, among other things. Self-assembly can lead to the transformation of graphene oxide (GO) into reduced graphene oxide (rGO) hydrogels, a commonly used carbon material that contains epoxide, hydroxyl (OH) functional groups, and carboxylic acid (COOH) groups. The graphene oxide/sodium alginate DN hydrogel had an exceptional ability to absorb Mn(II) (56.49 mg.g⁻¹). A novel approach was taken to assemble a graphene oxide/polyacrylic acid (GO/PAA) DN gel framework, in which GO sheets self-assembled during the solution polymerization process of acrylic acid (AA) monomers; two networks were formed simultaneously (Figure 8a). Due to their distinctive structure and properties, hydroxyapatite and sulfoaluminate cement were utilized to construct the inorganic network of the DN hydrogels. The inorganic substance was prepared in a uniform dispersion solution after stirring, called solution A. Then appropriate amounts of monomers and other chemical reagents were mixed in water to obtain solution B. Finally, the components were completely mixed at different temperatures to form DN hydrogels. The sulfoaluminate cement/polyacrylamide DN hydrogel made through hydration and radical polymerization is extremely strong because of its distinctive network structure and special chemical composition. The network of this hydrogel is comprised of hydroxyapatite (Figure 8b) [25].

Figure 8.

Schematic of the synthesis of GO/PAA DN gel and its adsorption behavior. (a) Schematic of the synthesis of sulfoaluminate cement/polyacrylamide DN hydrogel (1) and SEM image (2) and X-ray diffraction patterns (3) (b).

4.6 Ionic liquids

Biocompatibility, flexibility, and biocompatibility are all qualities that make hydrogels a natural carrier for drug delivery. Traditional PNIPAM-based hydrogel’s practical application is severely hindered by its poor drug compatibility. By adding a poly (ionic liquids) chain to the binary polymer chain, we synthesized a photo-thermally regulated smart hydrogel. The smart hydrogel is made transparent by the temperature-induced hydrophilic-hydrophobic switchable polymer chain, which allows for intuitive visualization of drug loading and release capacity. The smart hydrogel could be used as an NIR/temperature-controlled drug carrier to achieve efficient and visualized release (40.8% drug release rate in 30 min). A dynamic wound management system was created with the smart hydrogel, which has excellent sensing performance and editable drug delivery ability, to achieve personalized wound treatment and wireless state diagnosis. Wireless monitoring and warning of joints (fingers, ankles, and elbows) could be achieved by the wireless sensor early warning system, which has guiding significance for rehabilitation treatment. Furthermore, the sensor array that uses 5 × 5 smart hydrogels could accurately detect strain, temperature, and NIR light in three-dimensional space and direction. The smart hydrogel is a new approach to personalized wound diagnosis and assisted rehabilitation. By incorporating ionic liquids into the hydrogel, it not only retains their natural benefits but also enhances its solubility and conductivity. Ultrasonic-assisted radical polymerization resulted in synthesis of a smart hydrogel that is photothermally regulated. The smart hydrogel was given editable mechanical properties, transparency, and drug-loading capacity by the addition of poly (ionic liquids) chain to the polymer network (Figure 9). This enabled remote, rapid, and visualized drug release with a 40.8 percent release rate within 30 minutes [23]. The incorporation of ionic liquids (ILs) into hydrogel-enabled biosensing development has led to unique structures called ionic gels that have both the intrinsic attributes of hydrogels and ILs. The present review focuses on the two materials (hydrogels and ion gels) and their potential in biosensing applications in a straightforward manner. The most recent and impactful research is examined to provide a solid reference point for future development. Crosslinkers and initiators found in electrolytes play a role in the polymerization of aqueous ionic gels. Polyacrylamide-based hydrogels have been widely studied for their polymerization in the presence of KCl or NaCl-based electrolyte solutions. Polyethylene oxide and lithium salts are used to create a non-aqueous ionic gel that has recently been reported. The range of applications is limited by the low conductivity (10–5 S/cm) of lithium ions because of their mobility at room temperature. In order to improve the conductivity of ion gels, incorporating ionic liquids into polymer networks was a viable option. Dissolved salts with exceptional ionic conductivity and stability form ionic liquids (ILs) at temperatures below 100°C [26]. The report describes a hydrogel dressing that is both multifunctional and conductible, using a polymerized ionic liquid and konjac glucomannan (KGM). It was discovered that this newly developed hydrogel dressing has excellent mechanical properties and biocompatibility, as well as providing durable and efficient sterilization without releasing antibacterial factors. The current electrical stimulation was enhanced to significantly improve the migration and proliferation of fibroblast cells, as well as the treatment effect on diabetic skin wounds. A new approach to treating chronic wounds efficiently may be provided by a KGM hydrogel dressing that is polymerized and ionic liquid functionalized, along with ES. KGM, a polysaccharide that can be water soluble and flexible, can improve cellular metabolism by targeting specific sugar receptors in fibroblasts and is thought to be a promising material for building hydrogel dressing. A promising method for healing chronic wounds could involve ES and KGM-based hydrogel dressing. This purpose presents a challenge to developing hydrogel dressings based on KGM due to their poor electrical conductivity and weak antibacterial properties. The number of deaths caused by bacterial infections has risen significantly in modern healthcare, which is due to the overuse of antibiotics and the quick growth of multidrug-resistant pathogens. Numerous studies have been conducted on cationic antimicrobial polymers that have various cations, such as quaternary ammonium, phosphonium, pyridinium, and imidazole cations. PILs, which have large organic cations and small inorganic anions, are well-known for their high stability and excellent conductivity. It has been confirmed that they are promising candidates for ES treatment [27].

Figure 9.

Synthesis and application scheme of poly (ionic liquids) smart hydrogels.

5. Characterization of hydrogel

The characterization of hydrogels plays a crucial role in understanding their properties and potential applications. Various analytical techniques are employed to assess the structural, mechanical, and physicochemical characteristics of hydrogels. One commonly used method is scanning electron microscopy (SEM), which provides high-resolution images of the hydrogel’s surface morphology. This technique allows for the observation of the network structure, porosity, and homogeneity of the hydrogel. Additionally, Fourier-transform infrared spectroscopy (FT-IR) is used to analyze the chemical composition of hydrogels by detecting the vibrational modes of functional groups. By studying the FTIR spectra, one can identify the presence of specific chemical bonds and assess the degree of cross-linking within the hydrogel network. Light scattering techniques, such as dynamic light scattering (DLS), provide information about the size distribution and stability of hydrogel particles or aggregates in solution. Nuclear magnetic resonance (NMR) spectroscopy is another powerful tool for the characterization of hydrogels, providing insights into their molecular structure, mobility, and interactions. Furthermore, differential scanning calorimetry (DSC) can be utilized to investigate the thermal behavior of hydrogels, including the determination of phase transitions, glass transition temperature, and enthalpy changes. These techniques, including SEM, FT-IR, light scattering, NMR, and DSC, offer valuable insights into the structural, chemical, and thermal properties of hydrogels, enabling researchers to design and optimize hydrogel-based materials for various applications.

5.1 Methods to produce hydrogel

There are several methods available for the production of hydrogels, each offering unique advantages and considerations. One commonly used technique is the physical cross-linking method, where hydrogel formation relies on physical interactions, such as temperature, pH, or solvent-induced gelation. This method often involves the use of polymer chains with hydrophilic groups that can form reversible physical bonds, allowing the gel to swell and retain water. Chemical cross-linking is a method that uses cross-linking agents to create covalent bonds between polymer chains, leading to a stable network structure. This method offers excellent control over the gel’s mechanical properties and stability but requires the careful selection of crosslinkers and reaction conditions. Additionally, enzymatic cross-linking has gained attention as a more environmentally friendly approach, utilizing enzymes to catalyze the formation of cross-links within the hydrogel matrix. This method offers precise control over gelation kinetics and can be used with a variety of biocompatible materials. Furthermore, recent advances in 3D printing technology have enabled the fabrication of hydrogel structures with complex geometries and spatial control. This approach combines the use of hydrogel precursors with specialized 3D printing techniques, allowing precise deposition and layer-by-layer assembly of hydrogel-based constructs. Overall, the choice of hydrogel production method depends on the desired properties, application requirements, and the compatibility of the chosen materials. The general methods to produce physical and chemical gels are described below.

5.1.1 Physical cross-linking

Physical cross-linking is a common method for the production of hydrogels, relying on physical interactions to form a three-dimensional network structure. This approach utilizes factors such as temperature, pH, or solvent-induced gelation to induce gel formation. One popular method is thermally induced gelation, where the hydrogel precursor solution undergoes a phase transition upon a change in temperature. This can be achieved by either heating or cooling the solution, causing the polymer chains to undergo conformational changes and form physical cross-links. Another approach is pH-induced gelation, where the hydrogel precursor solution contains pH-sensitive groups that can undergo protonation or deprotonation, leading to gel formation. Additionally, solvent-induced gelation involves the use of solvents that can selectively swell the hydrogel precursor, promoting the formation of physical cross-links. The advantage of physical cross-linking is that it allows for the reversible nature of the gel, as the physical bonds can be broken and reformed under certain conditions. This provides the hydrogel with the ability to respond to external stimuli and exhibit stimuli-responsive behavior. Overall, physical cross-linking is a versatile method for producing hydrogels, offering control over gelation kinetics, gel properties, and the potential for application in areas such as drug delivery, tissue engineering, and biosensors. Physically cross-linked hydrogels can be obtained using various methods, as reported in the literature. Some of these methods include:

Heating/cooling a polymer solution: the physically cross-linked gels are formed by cooling hot gelatin or carrageenan solutions, with gel formation attributed to helix formation, helix association, and the formation of junction zones. Carrageenan undergoes conformational changes upon cooling, and the addition of salt promotes the formation of stable gels. Additionally, hydrogels can be obtained through warming polymer solutions, leading to block copolymerization (Figure 10) [28].

Figure 10.

The formation of gel occurs when helix aggregate when a hot carrageenan solution cools down.

Ionic interaction: The ionic polymers can be cross-linked by adding di- or trivalent counter ions, leading to gel formation. This principle is commonly applied in polyelectrolyte solutions, with examples including Na⁺ alginate and various chitosan-based hydrogels. Where multivalent ions of opposite charges, such as Ca²⁺ + 2Cl⁻, are introduced to initiate cross-linking (Figure 11) [29].

Figure 11.

Ionotropic gelation by interaction between anionic groups on alginate (COO⁻) with divalent metal ions (Ca²⁺).

Complex coacervation: complex coacervate gels form when a polyanion and a polycation are mixed. This is based on the principle of oppositely charged polymers binding together to create soluble or insoluble complexes, depending on solution concentration and pH (Figure 12). As an example, polyanionic xanthan has the ability to coacerbate with polycationic chitosan. Positively charged proteins have the ability to bind with anionic hydrocolloids below their isoelectric point to form poly-ion complex hydrogels or complex coacervates that contain poly-ion complexes [30].

Figure 12.

Complex coacervation between a polyanion and a polycation.

5.1.2 Chemical cross-linking

Chemical cross-linking is a process that involves the formation of covalent bonds between polymer chains, resulting in the creation of a three-dimensional network structure. This network provides enhanced mechanical strength, rigidity, and stability to the material. Chemical cross-linking is achieved by introducing cross-linking agents or molecules with reactive functional groups that can form bonds with the polymer chains. These reactive groups can include aldehydes, isocyanates, epoxides, or vinyl groups, among others. When the cross-linking agent reacts with the polymer chains, new chemical bonds are formed, effectively connecting the chains and immobilizing them in a fixed spatial arrangement. This cross-linking process can be controlled by adjusting parameters such as cross-linker concentration, reaction time, and temperature. These agents react with functional groups present in the polymers, such as OH, COOH, or NH₂, forming covalent bonds and creating cross-links. Common crosslinkers include aldehydes like glutaraldehyde and adipic acid dihydrazide. These cross-linking reactions can occur in both natural and synthetic polymers, allowing for the modification and enhancement of their properties. Chemical cross-linking is widely used in various industries, including polymer synthesis, coatings, adhesives, and the production of biomedical materials, where it enables the development of materials with tailored properties and improved performance. As reported in the literature, crosslinkers like glutaraldehyde and epichlorohydrin are widely used to create cross-linked hydrogel networks in both synthetic and natural polymers. This technique involves introducing additional molecules between polymer chains to form cross-linked chains (Figure 13). For example, glutaraldehyde can cross-link corn starch and polyvinyl alcohol to produce a hydrogel membrane with applications in artificial skin and targeted delivery of nutrients and medications [31]. Other examples include cross-linking carboxymethyl cellulose (CMC) with 1,3-diaminopropane for drug delivery, cross-linking xanthan and polyvinyl alcohol with epichlorohydrin, and cross-linking κ-carrageenan and acrylic acid using 2-acrylamido-2-methylpropanesulfonic acid for biodegradable hydrogels and drug delivery systems. Carrageenan hydrogels also show promise for industrial enzyme immobilization. Additionally, hydrogels can be synthesized from cellulose using epichlorohydrin and various methods involving NaOH/urea aqueous solutions [32, 33].

Figure 13.

Schematic illustration of using chemical cross-linker to obtain cross-linked hydrogel network.

6. Conclusion

In this current chapter, the history of hydrogels, their types and properties, their formation mechanisms, and their applications in food packaging, pharmaceuticals, agriculture, biomedicine, absorbents, and ionic liquids have been discussed. In the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Today, hydrogels widely play an important role in the production of products such as contact lenses, health products, and wound dressings. However, the production of commercial hydrogels for tissue engineering and drug release is still limited. Regarding the formation mechanism of hydrogels, there are different methods for the networks of the structure. The ability to swell upon contact with an aqueous solution is a desirable property of these hydrogels. This review examines the literature on how hydrogels can be classified based on their configurations, physical and chemical characteristics, and technical feasibility of utilization. Our review of nanoparticle-hydrogel composites has been extensive, as they are a state-of-the-art and versatile class of materials that can be used in a variety of applications. Many scaffolds and drug release tools based on hydrogels have been designed, studied, and, in some cases, even patented, but few of them have reached the market. Further development for the production of commercial hydrogels is expected in these two fields, but high production costs are the main reason for the limitation of their further commercialization. Recent advances in polymer science and technology have led to the development of various types of hydrogels. But despite all the beneficial properties of hydrogels, there are still many challenges to overcome for clinical transfer. Future research in this field will be focused on the transfer of promising preclinical studies and bioprocesses to change life with the ability to increase the quality of life and healthy aging on a global scale. The classification of synthetic approaches and applications of nanoparticle-hydrogel composites presented in this review is anticipated to enhance the reader’s understanding of the system and facilitate the design of innovative combinations for novel applications.

Acknowledgments

The authors appreciate the support from the University of Mazandaran. Also, the generous contributions of all our collaborators over the years are appreciated.

Conflict of interest

The authors declare no conflict of interest.