Comprehensive Review of Hydrogel Synthesis, Characterization, and Emerging Applications

Abstract

Hydrogels play a crucial role due to their high-water content and 3D structure, which make them ideal for various applications in biomedicine, sensing, and beyond. They can be prepared from a variety of biomaterials, polymers, and their combinations, allowing for versatility in properties and applications. Hydrogels include natural types derived from collagen, gelatin, alginate, and hyaluronic acid, as well as synthetic types based on polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide (PAAm). Each type possesses distinct properties, such as mechanical strength, biodegradability, and biocompatibility, which can be tailored for applications such as wound healing, contact lenses, 3D bioprinting, and tissue engineering. The high-water content of hydrogels mimics natural tissue environments, promoting cell growth and allowing nutrient and waste exchange, which supports the development of functional tissues. They serve as scaffolds in tissue engineering applications, including wound healing, cartilage and bone regeneration, vascular tissue engineering, and organ-on-a-chip systems. Additionally, hydrogels can encapsulate and deliver therapeutic agents, such as growth factors or drugs, to specific target sites in the body. Hydrogels can be prepared through three primary methods: physical crosslinking, which relies on non-covalent interactions such as physical entanglements or hydrogen bonding; chemical crosslinking, which forms covalent bonds between polymer chains to create a stable structure; and irradiation-based crosslinking, where UV irradiation induces rapid hydrogel formation. The choice of crosslinking method depends on the desired properties and applications of the hydrogel. By providing a biomimetic environment, hydrogels facilitate cell growth and differentiation, support tissue formation, and aid in the regeneration of damaged or diseased tissues while delivering therapeutic agents. This review focuses on the critical advancements in processing routes for hydrogel development, summarizing the characterization and application of hydrogels. It also details key applications, including wound healing and cartilage and bone regeneration, as well as the challenges and future perspectives in the field.

1. Introduction

The ability of hydrogels to create functional replacement tissues and organs holds immense promise for treating a wide range of injuries and diseases [1,2,3,4,5]. This includes advances in biomaterials science, 3D printing, stem cell technology, and bio fabrication methods. These innovations are driving the field forward and expanding its potential to address a wider range of tissue damage and diseases [6,7]. Normally, metal-based materials, chitosan, cellulose, and hydrogel materials are used for biomedical applications. Furthermore, hydrogel materials are used to support the development of new cells and promote repair. In general, hydrogel has large amounts of water, and it is one of the three-dimensional hydrophilic polymers [8]. They are highly biocompatible and can mimic the properties of natural extracellular matrices. Hydrogels are indeed fascinating materials with unique properties that have attracted significant attention from researchers. Their ability to retain a large amount of water is due to their 3D structure, which gives them a gel-like appearance and behaviour. The properties of hydrogels can be tailored based on the nature and arrangement of their constituent monomers, as well as the preparation method employed. The hydrogels are prepared using different methods like chemical cross-linking of monomers, physical cross-linking using temperature or pH changes, and blending of natural or synthetic polymers. These methods allow researchers to create hydrogels with specific properties suitable for various applications such as tissue engineering, biomedicine, and sensing. In tissue engineering, hydrogels serve as excellent biomaterials since they can mimic the natural water and polymer environment found in biological systems [9]. Hydrogels have gained popularity for their solubility, water retention, and wet environment compatibility. They are used in dye and heavy metal adsorption, biosensors, and medical coatings. However, traditional hydrogels struggle to combine electrical conductivity, strong adhesion, and mechanical performance. Designing hydrogels that adhere well to various surfaces while maintaining these properties is a significant challenge.

Hydrogels are three-dimensional networks of hydrophilic polymers that can absorb and retain large amounts of water while maintaining their structure. The water absorption capacity and network stability of hydrogels are controlled by crosslinking, which involves forming covalent or non-covalent bonds between polymer chains. Crosslinkers play a crucial role in providing secondary interactions with biological tissues, and the presence of hydrophilic groups in the polymer chains enhances water uptake [10]. Hydrogels possess several distinctive characteristics, making them highly valuable for various biomedical applications. These characteristics include biodegradability, biocompatibility, hydrophilicity, super absorbency, viscoelasticity, softness, and fluffiness. Furthermore, hydrogels are responsive to various stimuli, which adds versatility to their applications. These stimuli can include temperature, electric field, magnetic field, biological molecules, and ionic strength [11,12]. This resemblance to the extracellular matrix, along with their biocompatibility and biodegradability, makes them ideal for creating scaffolds to support tissue regeneration and growth. Smart hydrogels are a subcategory that can respond to external stimuli like pH, temperature, specific molecules, solvents, or mechanical force. These stimuli-responsive properties allow hydrogels to act as sensors for various applications. Additionally, the transportation properties and injectability of hydrogels make them promising candidates for drug delivery systems [13,14,15]. They can encapsulate and release drugs in a controlled manner, which is crucial for targeted and sustained drug applications. This review discusses the preparation methods for hydrogels, their characterization properties, and their use in various applications.

2. Types of Hydrogels

Hydrogels employed in pesticide encapsulation vary according to their material origins, which include natural polymers, synthetic polymers, and hybrid compositions combining both natural and synthetic polymers.

2.1. Natural Polymer

Natural polymer-derived hydrogels, sourced from plants or animals like polysaccharides and proteins, play a crucial role in encapsulating pesticides [16]. They are valued for their safety, biodegradability, and biocompatibility, ensuring environmentally friendly degradation after use. These hydrogels are adept at absorbing and retaining water, effectively managing pesticide release in soil to boost efficacy and minimize environmental harm caused by excessive application. Cellulose, abundant in nature, enhances pesticide encapsulation due to its structural characteristics. Derivatives such as carboxymethyl cellulose form networks that prevent leakage and prolong the release duration of pesticides [17]. Chitosan, derived from chitin, swells responsively to pH changes and interacts with other polymers to control release rates. Sodium alginate forms stable networks with calcium ions for controlled pesticide release, while proteins, with their amino acid chains, can be tailored for enzymatic degradation and precise pesticide release. Despite challenges like mechanical strength variations inherent in natural sources, natural polymer-derived hydrogels hold great promise for sustainable agriculture and environmental conservation. Ongoing research aims to enhance their properties for wider applications in pesticide encapsulation and precision agriculture.

2.2. Synthetic Polymer

Synthetic polymer hydrogels, such as those made from polyacrylamide (PAM) and PVA, are effective for pesticide encapsulation due to their controllable structures, mechanical strength, and chemical stability [18]. These properties enhance the longevity and stability of pesticide release, improving utilization. PAM is especially favoured for its water retention and non-toxic nature, making it prevalent in biomedicines and agriculture. However, the use of PAM comes with concerns. Acrylamide, used in PAM synthesis, is potentially neurotoxic and may release unreacted particles, posing environmental and health risks. Additionally, these hydrogels have low biodegradability, causing environmental residues and potential contamination. Production of these synthetic polymers often involves harmful chemicals, increasing costs and raising further health and environmental concerns [19,20].

2.3. Natural-Synthetic Polymer

Natural-synthetic polymer hydrogels, blending natural polymers like alginate and xanthan gum with synthetic counterparts such as PAM and PVA, offer innovative solutions for pesticide encapsulation in agriculture. These hydrogels enhance biodegradability and biocompatibility, mitigate long-term soil and water contamination risks, and provide robust mechanical strength and chemical stability. They effectively safeguard pesticides in diverse farm environments, ensuring controlled release according to preset conditions. Despite challenges in optimizing material ratios, eco-friendly synthesis, and cost reduction, these hydrogels represent a significant leap in pesticide encapsulation technology, promoting efficient pesticide use and sustainable agricultural practices.

3. Preparation Methods of Hydrogels

Hydrogels are composed of polymer chains, and the properties of the hydrogel are influenced by the properties of the polymer used. The main feature of hydrogels is their ability to absorb water, and not all polymers are suitable for synthesizing hydrogels (Figure 1). Polymer chains connect through cross-links to form a 3D network in hydrogels. Cross-linking affects various physical properties of the hydrogel, such as elasticity, viscosity, solubility, glass transition temperature, strength, toughness, and melting point (Figure 2). It has higher glass transition temperature due to limited rotational motion between the polymer chains. Cross-linking increases the molecular weight of the polymer chains, which, in turn, limits their translational movement and decreases the solubility of the polymer. These kinds of polymers are insoluble but can absorb a large amount of solvent, resulting in the formation of gels. The amount of solvent absorbed by the hydrogel depends on the cross-linking density, which increases as the interactions between the polymer chains and solvent molecules decrease.

Hydrogels can be prepared using two main methods: physical cross-linking and chemical cross-linking. These methods result in hydrogels with different properties due to the nature of the cross-links between the polymer chains. Ionizing radiations, such as X-rays, gamma rays, accelerated electrons, ion beams, and high-energy ultraviolet rays, can be used for polymerization reactions and crosslinking of polymers. These radiations have sufficient energy to break chemical bonds and initiate polymerization or crosslinking processes. In the context of polymerization reactions, ionizing radiation is used to initiate the polymerization of monomers and create long polymer chains. This process is known as radiation polymerization or radiation curing. It is commonly used in industries like coatings, adhesives, and 3D printing, where rapid and efficient polymerization is desired. Crosslinking is another essential process that can be controlled and intentionally modified using ionizing radiations. Crosslinking involves the formation of chemical bonds between polymer chains, creating a three-dimensional network structure. This network enhances the mechanical properties, stability, and other desirable characteristics of the polymer material. Controlling the crosslinking process with ionizing radiations can be achieved by manipulating various parameters during exposure, such as exposure time of radiation, frequency, temperature, and pressure. Figure 2 shows the hydrogels undergo different responses to changes in physical and chemical methods.

3.1. Hydrogel Formation Materials

Materials used for hydrogel formation include polyethylene oxide, PVA, poly(acrylic acid) (PAA), poly(propylene furmarate-co-ethylene glycol) (P(PF-co-EG)), and polypeptides. Some kind of materials are naturally derived polymers, including agarose, alginate, chitosan, collagen, fibrin, gelatin, and hyaluronic acid. Table 1 shows hydrogel preparation methods and doping elements.

3.2. Physical Cross-Linking

In physically cross-linked hydrogels, the interactions between polymer chains are not covalent but rather based on physical interactions. These interactions can include hydrogen bonding, van der Waals forces, hydrophobic interactions, or coordination bonds. Unlike chemical cross-linking, physical cross-linking is reversible under certain conditions, which means that the hydrogel can undergo structural changes without breaking any covalent bonds. This characteristic makes physically cross-linked hydrogels more responsive to external stimuli like temperature, pH, or ionic strength. They may exhibit unique properties, such as “self-healing” behaviour, where the gel can reform after being broken. The hydrogels prepared by these interactions are uniquely physical gels and have high water sensitivity and thermal reversibility. These kinds of hydrogel have a short lifespan, in the range of a few days to a maximum of a month, in the physiological media. Therefore, in this form, hydrogels are used when a short-term drug release is required. These kinds of hydrogels are safe to use for clinical purposes because the gelation does not require any toxic covalent crosslinking molecules. This method is used to prepare hydrogels through non-covalent approaches, such as electrostatic, hydrogen bonding, and hydrophobic forces among polymer chains. The physical methods used to prepare hydrogel have certain advantages, such as high-water sensitivity and thermal reversibility [21]. When prepared using this method, hydrogels are very safe for clinical purposes as the gelation does not require any toxic covalent crosslinking molecules. Chitosan with small anionic molecules such as sulphates, phosphates, and citrates of Pt, Pd, and Mo can be used for hydrogel preparation using physical methods. The synthesized hydrogels depend on the charge and size of anions and the concentration of deacetylation of chitosan.

Table 1

Preparation methods and variation of hydrogel.

Cross Link	Materials	Variation	Analysis	Ref.
Physical	Chitosan-silver	Composition, pH	Sol-gel, swelling, antimicrobial, mechanical, morphology	[22]
	Catechol-conjugated chitosan-thiolatedpluronic F-127 hydrogel	Composition	Tissue adhesion, mechanical, stability	[23]
	Chitosan	Composition, pH	Functional group, Rheology, Mechanical, degradation	[24]
Chemical	Poly vinyl alcohol, carbomer, glabridin	Composition	Swelling, mechanical, shape	[25]
	TiO2 loaded chitosan-poly (acrylic acid)	Composition	Removal of methylene blue, functional group analysis, morphology, thermal stability	[26]
	Polyethylene glycol	Mixing time duration	Rheological, mechanical, swelling,	[27]
	Acylated xylan, graphene oxide	Composition, pH	Functional group, morphology, particle size	[28]
	Chitosan/dopamine hydrochloride/inulin aldehyde hydrogel	Composition	Functional group, thermal, physical evaluation, statistical, cytotoxicity	[29]
	Polyvinyl alcohol	Composition	Tensile, Rheological, morphology, functional group, structural,	[30]
Irradiation	Chitosan-silver nanoparticles	Composition	Morphology, absorbance, particle size, Antimicrobial	[31]
	Sterculia gum	Composition (Graphene oxide)	Morphology, swelling, drug release studies, biomedical properties	[32]

3.3. Chemical Cross-Linking

The formation of physical gels through clustering of molecules causes formation of free chain loops and thus inhomogeneity that signifies short lived network imperfections. This preparation of hydrogel networks is easy to control when compared to physical hydrogels as their preparation and the applications they are used for are not dependent on their pH. The chemical crosslinking method can be used to transform the physical properties of the hydrogels. In chemically cross-linked hydrogels, covalent bonds form between the polymer chains. These covalent bonds are strong and stable, resulting in a 3D network of interconnected polymer chains. The cross-links are typically formed through chemical reactions, such as polymerization or cross-linking agent-induced reactions. The presence of covalent bonds makes the hydrogel structure more robust and resistant to changes in environmental conditions, such as temperature and pH. As a result, chemically cross-linked hydrogels generally exhibit greater mechanical strength and long-term stability. Chemically crosslinked hydrogels are easier to control as compared to physical hydrogels as their preparation method and applications are not dependent on their pH. Tan et al. [33] synthesized N-succinyl chitosan function alizedhyaluronic acid injectable composite hydrogels through a Schiff base mechanism. It was determined that the compressive modulus, which is an important factor for cartilage tissue engineering, improved with an increasing amount of N-succinyl chitosan in the hybrid hydrogel [33]. Ito et al. [34] also reported the same preparation method for hydrogel using cellulose and alginate. The amino group’s derivatives form hydrogels using Michael’s addition reactions. The amino groups react with the vinyl group of other polymers. In these kinds of preparations, hydrogels enhanced mucoadhesive properties. This method has some disadvantages, such as multistep preparation and purification method. Polymers might become cytotoxic after functionalization with the reactive groups.

3.4. Irradiation Based Cross Linking

Irradiation-based crosslinking is an attractive approach for hydrogel synthesis, especially in applications where rapid gelation and cost efficiency are critical factors. By harnessing light-sensitive functional groups and UV irradiation, researchers can achieve effective hydrogel formation in a short period, thus enabling various potential applications in biomedicine, tissue engineering, drug delivery, and other fields [13,14]. However, it is essential to consider specific requirements and potential limitations, such as the compatibility of the chosen light-sensitive moieties with the target application and the sensitivity of the hydrogel to environmental factors like light and temperature. The use of irradiation-based crosslinking with light-sensitive functional groups is a proposed method for the synthesis of hydrogels, and it offers several advantages over traditional chemical crosslinking methods [31]. It has some advantages such as (i) Speedy preparation: The hydrogel formation can occur rapidly when using light-sensitive functional groups and UV irradiation. This allows for a faster production process compared to chemical crosslinking methods, which may involve longer reaction times; (ii) Low cost of production: The use of light-sensitive functional groups and UV irradiation may reduce the need for expensive crosslinking agents or catalysts, potentially making the production process more cost-effective [32].

The proposed method by Ono et al. [35] for the synthesis of UV-light irradiated chitosan hydrogels is based on the use of light-sensitive moieties, specifically azide and lactose. Azide and lactose are introduced into the chitosan polymer. These moieties are selected because they are sensitive to UV light and can undergo specific reactions upon exposure. The chitosan polymer with the introduced azide and lactose moieties is exposed to UV light. UV light serves as a trigger to initiate a reaction involving the azide group. Upon UV irradiation, the azide group on the chitosan polymer is converted into a nitrene group. This conversion is likely a photochemical reaction, where the high-energy UV light breaks the N-N triple bond in the azide group, generating a reactive nitrene intermediate. The generated nitrene intermediate then reacts with the amino groups present in chitosan. The nitrene group binds covalently to the amino groups, resulting in the crosslinking of chitosan chains. This crosslinking process forms a three-dimensional network, leading to the formation of a hydrogel.

The irradiation-based cross linking method reported by Yoo et al. [36] for the synthesis of UV-irradiated chitosan hydrogels involves pre-functionalization with photo-sensitive acrylates of chitosan and pluronic acid. However, this method has some drawbacks such as need for a light sensitizer, delayed irradiation, and increase in local temperature.

4. Characterization Methods

4.1. Swelling

The swelling of a hydrogel refers to the process of absorbing a significant amount of water, leading to an increase in its volume and weight. It is an essential property of hydrogels and has a significant impact on various characteristics, including the degree of cross-linking, mechanical properties, and rate of degradation. Several methods are used to measure the swelling of hydrogels, such as gel fraction study, swelling ratio measurements, and the weight loss method. These methods are relatively simple and widely used to assess the swelling behaviour of hydrogels. By understanding their swelling properties, researchers can gain insights into the structure and performance of hydrogels, which is crucial for various applications, such as drug delivery, tissue engineering, and biomedical devices. Additionally, the swelling behaviour can provide valuable information about the hydrogel’s response to changes in the surrounding environment, making it an important consideration in material design and engineering. The swelling of a hydrogel is determined using gel fraction [37]

$\mathrm{Swelling}={\displaystyle \frac{{\mathrm{W}}_{\mathrm{s}}-{\mathrm{W}}_{\mathrm{i}}}{{\mathrm{W}}_{\mathrm{i}}}}$

where, Ws—the dry weight of polymer after the treatment and Wi—the dry weight of the as prepared polymer. Li Q et al. [38] reported that the swelling kinetics of PDIV1-PDIV4 (Figure 3a) exhibit rapid swelling during the first 10 h, reaching equilibrium by 12 h with rates of 5.3 g/g, 10.73 g/g, 14.55 g/g, and 19.41 g/g. This rapid swelling is attributed to the ionization of carboxyl groups in deionized water, where increased itaconic acid content enhances water absorption and loosens the hydrogel structure. As shown in Figure 3b, the swelling rate decreases with increasing temperature, following the order PDIV1 < PDIV2 < PDIV3 < PDIV4. At lower temperatures, strong hydrogen bonds between hydrophilic groups and water molecules promote water absorption. However, as the temperature rises, these hydrogen bonds weaken, while internal hydrogen bonds within the hydrogel increase, resulting in reduced volume and swelling rate. Figure 3c illustrates the swelling-shrinking behaviour of PDIV1-PDIV4 between 25 °C and 37 °C. In Figure 3d, swelling initially decreases and then increases with changing pH. At pH 2, the swelling order is PDIV1 > PDIV2 > PDIV3 > PDIV4, but this order reverses at pH 4 and higher. In strongly acidic conditions (pH 2), protonated amide groups increase molecular repulsion, limiting water absorption. Between pH 2 and 6, hydrogen bonds between carboxyl and amide groups dominate, causing the hydrogel to contract. At pH 6 or higher, weaker hydrogen bonds and stronger interactions with water molecules expand the hydrogel, with higher IA content leading to greater swelling. Figure 3e shows the swelling-shrinking behaviour between pH 1.2 and 7.4.

4.2. Microstructural Performance

The microstructure of hydrogels plays a crucial role in determining their physical properties and behaviour. Several key parameters are used to characterize the microstructure of hydrogels such as volume fraction of the polymer in the swollen state, number average molecular weight between cross-links, mesh size of the network, and other environmental factors. The mesh size depends on the degree of cross-linking, chemical structure of the monomers, and the external environment, especially pH, temperature, and ionic strength. The mesh size calculates the physical properties of the hydrogel, including mechanical strength and the degradability and diffusivity of a releasing molecule [39]. The microstructure of hydrogels is vital for tailoring their properties to specific applications, such as drug delivery, tissue engineering, and biomaterial design. By controlling the degree of cross-linking and mesh size, researchers can customize the mechanical properties, degradation rate, and release kinetics of the hydrogel, making it a versatile and valuable material in various biomedical and engineering fields. Zhang et al. [40] investigated the microstructure of hydrogels using SEM to understand the effects of MTG crosslinking. The M7-crosslinked hydrogel had a denser, smoother reticulate surface compared to natural and WT-crosslinked versions (Figure 4a). Internally, it featured a distinctive polygonal or honeycomb structure (Figure 4a). These structural improvements are due to the combined effects of hydrogen bonding, hydrophobic interactions, and covalent bonding from MTG crosslinking, enhancing the hydrogel’s microstructure and its potential uses in the food industry. Khalesi et al. [41] found that Figure 4b,c displays SEM images of SAF- and LAF-WPI hydrogel composites with varying NaCl concentrations. SEM analysis at ×40,000 (Figure 4b) and ×10,000 magnifications (Figure 4c) showed that increasing NaCl levels enlarged pores and altered the microstructure, with 150 mM NaCl leading to the most noticeable coarseness. High NaCl concentrations reduce electrostatic repulsion among proteins, promoting larger aggregates. These results are consistent with other studies on pH changes, ion additions, and biopolymer interactions. Moreover, LAF-hydrogel composites with 150 mM NaCl exhibited more branching, indicating that fibril length and NaCl affect gel morphology. Camerco et al. [42] reported that SEM images (Figure 5) show ellipsoidal hydrogel beads, with SA beads having a rougher surface compared to smoother SA-TSM beads, indicating TSM’s role in structural improvement. Cross-sections reveal SA beads are more porous, while SA-TSM beads have a more uniform structure with fewer cracks, suggesting TSM enhances structural support. The bead size ranged from 2.09 to 2.91 mm, increasing with TSM due to higher viscosity. The beads were not perfectly spherical (SF > 0.05), and TSM-containing beads had a lower SF, indicating better cross-linking and uniformity (Figure 5).

4.3. Mechanical Properties

The mechanical properties were determined from normal techniques such as tensile testing, compression testing, indentation testing, bulge testing, cyclical testing, and the strip extension method. This test is demonstrated in the following ways. Tensile testing is a common technique used to determine the mechanical response of a material to an applied tensile force. In the case of hydrogels, this involves subjecting a strip of the hydrogel to a tensile force using specialized grips in an instrument. The resulting stress-strain data can be used to calculate important mechanical properties, such as Young’s modulus, yield strength, and ultimate tensile strength [43]. Compression testing involves placing a hydrogel sample between two plates and applying pressure to compress it. This helps determine the compression distance or how the hydrogel responds to compressive forces. By analysing the deformation and load data during compression, researchers can understand how the hydrogel behaves under compressive stresses. Indentation testing involves pressing a small, hard object into the surface of a hydrogel. The indentation depth and the force applied are measured to understand the hydrogel’s hardness and elastic modulus in the indentation region. The bulge test is a specialized test used to measure the mechanical properties of thin films or membranes, including hydrogels. In this test, a hydrogel sheet is constrained around its edges while being subjected to internal pressure. By monitoring the deformation, researchers can extract properties like the elastic modulus and Poisson’s ratio of the hydrogel. Cyclical testing, also known as fatigue testing, involves subjecting the hydrogel to repetitive loading and unloading cycles. This helps assess the material’s fatigue behaviour, which is essential in understanding its long-term mechanical durability under repeated stresses. Zhang et al. [44] tested hydrogels using an AGS-X machine at 20 °C and 80% humidity. Hydrogels, prepared in cuboid moulds and hydrated, were evaluated for tensile strength (10 mm × 8 mm × 40 mm) and compression (20 mm diameter) at 1 mm/min. Adhesion tests with T-AlgDD on cellulose membranes were light-treated and soaked in CaCl₂ before testing. S-Alg showed low tensile Young’s modulus (2.7 ± 0.7 kPa) and high elongation (224%), while D-Alg had higher tensile modulus (134.6 ± 6.2 kPa) and compression modulus (453.9 ± 16.9 kPa) (Figure 6a,b). AlgMA’s double crosslinking improved strength but reduced toughness. Figure 6c illustrates the linear viscoelastic region determined by an amplitude sweep conducted prior to the oscillatory frequency sweep tests on S-Alg and D-Alg, which were performed to further investigate their three-dimensional network structures. Figure 6d shows that both S-Alg and D-Alg hydrogels display a wide linear viscoelastic range, extending up to about 10% strain. The storage modulus (G’) is greater than the loss modulus (G”), and remains constant across the frequency range, which is typical of hydrogel viscoelastic behaviour. Notably, D-Alg has a higher storage modulus than S-Alg, highlighting its improved mechanical properties. Hou et al. [45] found that PVA-CMC hydrogels exhibited excellent mechanical properties for soft strain sensors through stress-strain, tensile, and cyclic tests (Figure 7). The hydrogel strip (3.5 mm thick, 4.5 mm wide) supported 1 kg without damage and withstood stretching, twisting, and knotting (Figure 7a). It retained its structure after stretching, poking (Figure 7b), or drill pressure (Figure 7c). Adding DMSO decreased the fracture strain of pure PVA from 446.48% to 241.18% while increasing the maximum fracture stress to 0.366 MPa. The addition of CMC further improved strength and strain (0.453 MPa, 272.13%) (Figure 7e). The PVA-CMC hydrogel displayed notable hysteresis and stable performance in cyclic tests (Figure 7f–h). DMSO enhanced crosslinking density, leading to improved energy dissipation and fatigue resistance (Figure 7i). Hardness tests indicated that Ag-CMC hydrogels had higher values than pure PVA (Figure 7m), and Ag(1.0)-CMC(0.08) hydrogels achieved optimal mechanical strength and low resistance (Figure 7n,o).

4.4. Morphology Study

Morphology studies in the context of hydrogel research are essential for understanding the structural characteristics and physical properties of the prepared hydrogels. FE-SEM is used to examine the surface morphology and topography of hydrogels. It provides high-resolution images of the hydrogel’s surface, revealing its surface features, such as porosity, roughness, and the presence of any structural defects [46]. Environmental Scanning Electron Microscopy (ESEM) allows for imaging under controlled environmental conditions, including in the presence of water, making it suitable for studying hydrogels. ESEM can reveal the morphological changes that hydrogels undergo in a wet state, which is crucial for understanding their behaviour in physiological or aqueous environments. Transmission Electron Microscopy (TEM) is used to study the internal structure of hydrogels at the nanoscale. It provides information about the particle size and shape of components within the hydrogel [47]. It can also reveal the distribution of nanoparticles or other inclusions, if present. For FE-SEM and ESEM, the hydrogel samples are typically dehydrated, coated with a conductive layer like gold or carbon, and imaged under high vacuum conditions or in a controlled environmental chamber. For TEM, ultrathin sections of the hydrogel or nanoparticles within it are prepared, stained or contrasted if necessary, and examined using high-vacuum TEM. Huang et al. [48] developed a MnO₂-embedded 3D porous PANI hydrogel electrode for supercapacitors. As shown in Figure 8, the hydrogel’s coral-like porous structure supports efficient electron transfer. SEM (Figure 8b) reveals a sturdy surface, while TEM (Figure 8c) shows uniformly distributed MnO₂ nanoparticles coated with a 20–50 nm PANI layer for protection. The electrode displayed a specific capacitance of 293 F/g at 10 mV/s with 1.5 mg/cm² loading, decreasing to 258 F/g at 10.8 mg/cm², benefiting from its conductive, porous structure.

4.5. Fourier Transform Infrared Spectroscopy (FTIR)

The chemical structure and bonds are identified by FTIR. Those chemical bonds can be excited and absorb infrared light at frequencies that are typically based on structure and bonds. Molecules have characteristic vibrational frequencies associated with their chemical bonds, and when these bonds are exposed to infrared radiation, they absorb energy at specific frequencies [49]. Each type of bond absorbs infrared light at distinct frequencies based on factors such as bond strength and the masses of the atoms involved. Analysing the absorption pattern of infrared light by a hydrogel helps identify the functional groups and chemical structures of the compounds present. Medha et al. [50] reported that Figure 9a illustrates the FTIR spectra of chitosan, starch, chitosan-starch hydrogel, and cefixime-loaded hydrogel. All spectra show broad bands between 3300 and 2850 cm⁻¹ for -OH, -NH₂, and -CH stretching. Chitosan features bands at 1645 cm⁻¹ (C=O stretching), 1548 cm⁻¹ (-NH bending), and 1380 cm⁻¹ (-CH₃ deformation). Starch shows a weak peak at 1650 cm⁻¹ (OH bending) and bands at 1436 cm⁻¹ and 1340 cm⁻¹ (CH deformation). The chitosan-starch hydrogel displays a band at 1653 cm⁻¹, indicating grafted polyacrylamide and crosslinking. Cefixime’s spectrum has peaks at 1768, 1669, 1588, 1537, and 1384 cm⁻¹ for different functional groups. The shifts in -OH and -NH₂ bands in the cefixime-loaded hydrogel suggest drug-polymer interactions. Enoch et al. [51] presented FTIR spectra of chitosan/alginate hydrogels at various concentrations (Figure 9b). The alginate hydrogel (C0A) shows peaks at 3298 cm⁻¹ (O-H stretching), 2110 cm⁻¹ (C-H stretching), 2335 cm⁻¹ (CO₂), and 1637 cm⁻¹ (COO− stretching). Chitosan/alginate hydrogels (C1A to C5A) show a broad band at 3260 cm⁻¹ due to overlapping O-H and N-H stretching. Peaks at 1019 cm⁻¹ and 1083 cm⁻¹ correspond to C-O and C-H stretching, while peaks at 1404 cm⁻¹ and 1596 cm⁻¹ indicate amine-aldehyde interactions and COO− stretching, respectively.

4.6. Antimicrobial Characteristics

Recent research has focused on advancing natural polymer hydrogels for versatile applications through methods like double-network, nanocomposite, macromolecular microsphere composite, and polyampholyte hydrogels. These hydrogels, known for their high-water absorption, elasticity, flexibility, self-healing abilities, and biocompatibility, are widely used in tissue engineering, drug delivery, food packaging, cosmetics, and biomedical applications. Significant efforts have been made to develop antibacterial hydrogels as alternatives to traditional materials, achieving desired properties such as hydrophilicity and porosity through careful selection of monomers and crosslinkers. Antibacterial hydrogels encompass types incorporating inorganic nanoparticles, infused with antibacterial agents, and inherently antibacterial varieties, with silver nanoparticles effectively disrupting bacterial DNA replication. Key components include natural and synthetic polymers like alginate, chitin, chitosan (CHT), and carboxymethyl cellulose (CMC). Studies have emphasized using chitin-based materials to combat antimicrobial resistance in E. coli, showcasing combinations like Ag₂Mo₂O₇/chitin and CHT/2-glycerophosphate/nano-silver hydrogels [52]. Krishnana et al. [53] assessed the antibacterial activity of six hydrogel samples against Escherichia coli (E. coli) using the inhibition zone (IZ) method. E. coli suspensions were adjusted to a concentration of 6.8 × 10⁵ CFU/mL following a 24-h incubation at 37 °C. Circular hydrogel samples (8 mm in radius, 2 mm in thickness) were placed on agar plates containing the bacteria and incubated for 8 h at 37 °C. The IZ diameters were measured using a Vernier calliper and verified with Image J software (Figure 10). Samples without CuNPs (S1 to S4) displayed satisfactory antibacterial effects, while those with CuNPs showed enhanced antibacterial resistance, with sample S6 (containing 1% w/v CuNPs) demonstrating the highest activity. Wan et al. [54] found that polyvinyl alcohol (PVA)/phytic acid (PA)/glycerol (GL) hydrogels exhibited strong antimicrobial activity against E. coli and Bacillus subtilis, forming distinct inhibition zones due to the acidic nature of PA, which disrupts bacterial membranes (Figure 11a). In contrast, PVA/GL hydrogels did not show inhibition. The PVA/PA/GL hydrogels significantly suppressed bacterial growth, with inhibition zones measuring 25 mm for Bacillus subtilis and 24 mm for E. coli. The hydrogels demonstrated consistent antimicrobial properties over 7 days, making them ideal for long-term use in skin-contact sensors (Figure 11e,f).

4.7. Self Healing Characteristics

Self-healing materials, which can autonomously repair damage, are increasingly common in hydrogels. These mechanisms depend on dynamic covalent bonds (e.g., Diels–Alder, imine, disulfide) and non-covalent interactions (e.g., hydrogen bonds, hydrophobic interactions). Natural polysaccharides like alginate and chitosan, as well as synthetic polymers like PEG and PVA, are used to create biocompatible, strong, and flexible self-healing hydrogels. Combining Li alginate with poly(acrylamide-co-stearyl methacrylate) results in hydrogels with high fracture energy and fire resistance [55]. Rapid self-healing hydrogels utilize flexible polymer networks for quick repairs, and innovations include fluorochromic and Schiff base linkage-based hydrogels that self-repair at room temperature [56]. Two hydrogels of different colours (one red with rhodamine B) were cut and placed together. After 10 min, they autonomously adhered and healed without external force, demonstrating fast self-healing. Some dye diffusion blurred the interface, but the hydrogel could still stretch without cracking, indicating recovery of its 3D structure and mechanical strength. Rheological analysis showed rapid recovery of the hydrogels’ internal structure, with storage modulus G’ rising from 200 Pa to 2016 Pa, matching the original value. Under varying oscillatory forces, the hydrogels exhibited a thixotropic, elastic response, confirming their self-healing ability [57].

4.8. Delivery Characteristics

Smart hydrogels, ideal for studying cell and drug delivery interactions, require advanced designs informed by pathology, polymer science, and therapeutic methods. A new scientific approach is emerging to develop smart materials for biological applications, specifically targeting diseases that disrupt homeostasis. Recent innovations include smart systems for inflammation, cancer, and diabetes, aiming for self-assembling therapeutic delivery. Building on knowledge gained from other tissues, the ongoing development of self-assembling peptides will enhance our ability to precisely control the microenvironment they create for embedded cells.

While the field of smart biomaterials has been under investigation for some time, it continues to evolve. Smart materials are designed to sense changes in their surroundings and respond accordingly, which may involve degradation, growth factor release, or other adaptive adjustments. For example, Altunbas et al. [58] reported a study analysing the delivery of curcumin using MAX8 peptide hydrogels and its impact on the behaviour of DAOY human medulloblastoma cells. The study focused on how varying concentrations of the hydrogel affected the release rate of curcumin and its ability to induce cell death. It investigated the self-supporting properties of the hydrogel, the controlled release of curcumin, and its effectiveness in inducing apoptosis in cancer cells through mechanisms involving caspase 3 and PARP activation. The findings suggest that the hydrogel system can serve as a sustained-release platform for curcumin, potentially enhancing its therapeutic effects in cancer treatment [58].

In addition, for protein therapeutics to be effective, they must reach their target site protected from degradation and remain long enough to exert their effects, which is particularly challenging in organs other than the liver. Delivering proteins to the heart is especially difficult due to constant blood flow, making localized delivery more effective than systemic approaches. Techniques such as intracoronary infusion or intramyocardial injection can create a local protein reservoir, but rapid dilution into the bloodstream poses challenges. Biomaterials that provide sustained release represent promising solutions, ensuring controlled delivery while preserving protein bioactivity and biocompatibility. Despite numerous studies on various materials, many do not meet all necessary criteria. Self-assembling peptide hydrogels have shown significant potential for sustained protein release in regenerative applications. This section examines their utility in treating myocardial infarction and suggests design improvements for their delivery systems [59].

4.9. Viscoelastic Properties

Rheology or compression testing is commonly used to evaluate the viscoelastic properties of hydrogels, and these properties are summarized in Table 1. The viscoelastic behaviour of hydrogels can be modulated by varying polymer and crosslinker concentrations, which influences their stiffness and elasticity [60]. For instance, higher crosslinker concentrations in glutaraldehyde-crosslinked gelatin hydrogels increase stiffness and shift the material toward a more elastic state. Additionally, modifying the viscosity of the aqueous phase with dextran in agarose and polyacrylamide hydrogels allows for control over viscoelastic properties while maintaining a stable elastic modulus, enhancing the design of hydrogels for biomedical applications. Viscoelasticity in hydrogels arises from several molecular mechanisms, particularly in physically or non-covalently crosslinked systems. When stress is applied, crosslinkers can detach and allow the polymer matrix to flow, then reattach, as seen in weakly crosslinked collagen gels, alginate gels, and PEG hydrogels. Other factors, such as polymer entanglement and protein unfolding, also contribute to viscoelasticity by dissipating energy and enabling reversible elastic responses [61]. Even in well-crosslinked hydrogels, the significant water content leads to energy dissipation, resulting in a measurable loss modulus without inducing plasticity.

5. Applications

5.1. Wound Healing

Super absorbent hydrogels, also called super porous hydrogels, can absorb up to 90% of their weight in water without breaking down, making them ideal for wound healing dressings, such as alginate-based hydrogels. They offer bioadhesive and sealant mechanisms, providing alternatives to staples or sutures. Wound healing has four phases: homeostasis, inflammation, proliferation, and remodelling [62,63]. Delays in healing, especially beyond three months, can lead to chronic wounds, often due to prolonged inflammation. Hydrogel dressings are effective for chronic wounds because they can be customized with growth factors, biomolecules, and drugs. Adding anti-inflammatory agents like phenolic compounds from honey or plant extracts can enhance hydrogels, speeding up healing by reducing inflammation. Xin et al. [64] developed a hydrogel for diabetic wound healing by combining oxidized Gastrodia elata polysaccharide (OGEP) with a gastrodin-chitosan compound (GAS/CS) through a Schiff base reaction. The hydrogel, loaded with EGCG microspheres, was tested for therapeutic effects on diabetic wounds, as well as its biosafety, rheology, and hemostasis properties (Figure 12).

5.2. Contact Lenses

Contact lenses are mainly used as an alternative to spectacles for vision correction [60]. They are also being developed for drug delivery, corneal defect treatment, post-surgical wound repair, and cosmetic purposes [65,66]. Traditional methods like eye drops and ointments have drawbacks, such as limited permeability and frequent dosing [67]. Thus, contact lenses are being explored as a promising option for ophthalmic drug delivery [67]. Ideal contact lens materials should be durable, stable, clear, and allow adequate oxygen to the cornea [68]. Lens characteristics include mechanical, optical, and chemical aspects. Wettability maintains a stable tear film, while mechanical testing impacts comfort, fit, and durability. Optical properties ensure good vision [68]. Hydrogels are recommended due to their high compatibility with corneal cells [69]. Hydrogels have advanced clinical ophthalmology through their use in SCL, IOL, and drug-eluting hydrogels, focusing on the eye’s anterior segments [70]. Polymeric hydrogels, like pHEMA, are popular for SCL and drug delivery [71]. Compared to rigid lenses, SCL offer higher water content, softness, elasticity, and oxygen permeability. IOLs, primarily hydrogels, are used in cataract surgery to replace the natural lens. Drug-loaded IOLs can improve drug delivery by reducing losses and side effects and lessening patient compliance issues [72]. Yang et al. [73] reported that electrodeposition enables the production of chitosan-based hydrogel contact lenses with enhanced transmittance, mechanical strength, oxygen permeability, and resistance to Staphylococcus aureus (Figure 13). This method also induces efficient cross-linking of chitosan and epichlorohydrin, presenting a novel approach for contact lens fabrication.

5.3. Tissue Engineering

Hydrogels are notable for their versatility in drug delivery and tissue engineering [74]. Tissue engineering regenerates tissue by integrating cells with a scaffold under physiological conditions [75,76]. The essential elements, or “triad,” are cells, scaffolds, and growth factors [75,76,77]. Hydrogels, used as scaffolds, support cell attachment, growth, and tissue regeneration [76]. Their 3D polymer networks retain significant water, making them ideal for this purpose [76]. Hydrogels can be customized to mimic the extracellular matrix (ECM) of native tissues through various crosslinking methods [77]. Most ECMs are porous networks, similar to hydrogels, with fibrous proteins in a matrix of glycosaminoglycans (GAGs) and proteoglycans [77]. Hydrogels are key in tissue engineering for repairing dermal tissue, cartilage, blood vessels, bone, cornea, and other soft tissues [78]. They effectively mimic the ECM, making them ideal for replacing damaged tissues [79]. Cartilage, which lacks lymphatics, blood vessels, and nerves, relies on ECM for maintaining cell microenvironment homeostasis. Cartilage scaffolds need excellent biocompatibility, porosity, and mechanical strength, resembling Type II collagen. Elastic hydrogels with smooth surfaces and high-water content are ideal for cartilage regeneration as they closely mimic the ECM [80]. Mei Liu et al. [81] reported that the schematic illustrating injectable hydrogels for cartilage and bone tissue engineering applications is shown in Figure 14.

5.4. 3D Bioprinting

Bioprinting with hybrid hydrogels integrates the benefits of both technologies, supporting layer-by-layer printing with solid filament structure and physical gelation during extrusion [82,83]. These hydrogels enhance cell functions crucial for tissue engineering, including proliferation, migration, and differentiation. Extrusion-based bioprinting is favoured for its compatibility with low-viscosity hydrogel precursors [84]. Hydrogel bioinks, composed of cells and precursor solutions, are essential for replicating tissues and organs in bioprinting, requiring optimal rheological and biochemical properties [85,86]. Various crosslinking methods and bio ink formulations have been developed to mimic specific tissue architectures, demonstrating effective printing with materials like HA-based bioink crosslinked with calcium solutions [87,88]. Boons et al. [89] created a 3D bioprinting platform to produce hydrogels with live dialgae, used as biological indicators for water quality. These hydrogels, exposed to different concentrations of salt, herbicides, and antibacterial agents, allowed visual assessment of diatom proliferation to detect water contaminants. The diatoms stayed metabolically active in the hydrogels, enabling pollutant sensitivity testing. Additionally, engineered bacteria such as Deinococcusradiodurans and E. coli have been used for infrared detection, but they need appropriate substrates for environmental adaptation [90]. Tainara et al. [91] detailed 3D bioprinting as an innovative approach in tissue engineering and regenerative medicine for creating biological substitutes and artificial organs. It efficiently builds complex structures using cells and biomaterials, guided by CAD programs. The process involves medical imaging, bio-modelling, ink formulation, printing, and analysis, providing flexibility, precision, and customization. He et al. [92] 3D-printed a hydrogel structure (Figure 15) with 2.5% (w/v) SA and 8% (w/v) gelatin. The nozzle was at 37 °C and the substrate at 5 °C, with parameters set to P = 20 kPa, D = 0.3 mm, H = 0.1 mm, and F = 4.45 mm/s. The line width was 0.65 mm due to diffusion, versus 0.6 mm theoretically. The 30-layer structure, with each layer 0.57 mm thick, maintained precision in the first 25 layers (Figure 15ii(b–d)). Angles were corrected for tilts up to 30°, and layers were printed with 40 s delays. A 2% CaCl₂ solution was used to solidify the structure through ionic crosslinking.

5.5. Bio Sensors

Hydrogels, used in electronic skin and wearable biosensors, offer numerous advantages. They are flexible, elastic, and adhere well to human skin, providing enhanced comfort. Their water absorption helps keep the skin moisturized and stable, and their conductivity ensures reliable signal transmission. Traditional methods for designing advanced hydrogels are challenging, as they require adding many components to improve various properties. AI technology helps by efficiently screening and optimizing hydrogel components. High-throughput screening has led to the development of polysulfobetaine hydrogels with excellent mechanical and self-healing properties, expanding their use in flexible electronics and enhancing intelligent functions like real-time health monitoring and wireless communication. AI-integrated hydrogels can accurately recognize handwriting movements, making them ideal for smart human-device interfaces. Further research is needed to ensure the stability, safety, and privacy of these applications. Diaconu et al. [93] immobilized laccase from Trametes versicolor into a nanocomposite film using a MWCNT-CS solution with 25 U/mL laccase. The conducting MWCNTs made the Au/Lacc-CS-MWCNT biosensor five times more sensitive to micromolar concentrations than other polyphenol biosensors. The CS-MWCNT layer-maintained enzyme specificity and enabled real-time polyphenolic content monitoring in plants. MWCNTs also improved electrode properties by enhancing charge transfer. Zaninia et al. [94] developed a biosensor by immobilizing lactate oxidase on a GCE modified with laponite/CS hydrogels to measure l-lactate in alcoholic beverages and dairy products. This biosensor effectively determined l-lactate in food samples like white wine and fermented milk without pretreatment, maintained high catalytic activity for over 30 days, and allowed interference-free l-lactate measurement with a low applied potential.

5.6. Supercapacitor

A supercapacitor is an energy storage device that uses ion adsorption or reversible Faradic reactions. The technology has advanced with the development of nanostructured electrode materials. High-performance supercapacitors are created by increasing the electrode surface area and stabilizing electrolyte solutions [95,96,97]. Nanomaterials like nanoscale activated carbon are popular due to their large surface area and low cost, though their energy storage capacity is usually below 200 F/g. Graphene coupled with hydrogel offers greater potential for supercapacitors due to its high surface area, nano-micropore network, and multidimensional electron transport pathways. The first graphene/hydrogel-based ultrafast supercapacitor achieved 113.8 F/g and 205.0 kW/kg power density [98]. A flexible solid-state supercapacitor using a 3D graphene hydrogel film provided 186 F/g specific capacitance and 372 mF/cm² area-specific capacitance, with excellent rate capability [99]. Moussa et al. [100] evaluated PANi-NF hydrogels as supercapacitors using a two-electrode system in 1.0 M H₂SO₄ (Figure 16i). Cyclic voltammetry (CV) at 5 mV s⁻¹ exhibited quasi-rectangular profiles with characteristic PANi redox peaks. Competitive CV behaviour was observed across different scan rates, while galvanostatic charge/discharge curves at varying current densities showed deviations from linearity due to pseudocapacitance. The PANi-NF hydrogel achieved gravimetric and areal capacitances of 492 F g⁻¹ and 271 mF cm⁻² at 1 A g⁻¹, surpassing previously reported values. However, its performance declined at higher current densities, likely due to the low conductivity and high internal resistance of the polymer framework. Xu et al. [101] fabricated a graphene/PEDOT:PSS hydrogel fibre-based supercapacitor, tested at −20 °C after 1 h. Figure 16ii(a) shows GCD curves, with specific capacitance decreasing from 212.6 F/g at 0.1 A/g to 76.8 F/g at 1.6 A/g. Figure 16ii(b) presents CV plots, exhibiting nearly rectangular shapes, indicating strong rate capability. In Figure 16ii(c), connecting three cells in series extends the voltage window from 0.8 V to 2.4 V, with the inset showing practical use. Figure 16ii(d) demonstrates stability at various bending angles. Figure 16ii(e) shows 91% capacitance retention after 5000 cycles. Figure 16ii(f) illustrates the tandem cell powering an electronic watch at sub-zero temperatures.

5.7. Catalysis

Hydrogels are widely used in biological and chemical catalytic reactions due to their unique structure and porosity. They prevent nanoparticle aggregation, increasing the surface area available for catalysis, which in turn boosts reaction efficiency. The porosity of hydrogels can be adjusted by environmental conditions, allowing precise control over reaction rates. Additionally, functional groups within the hydrogel matrix stabilize metal nanoparticles, protecting them from oxidation. Hydrogel-embedded metal nanocatalysts are commonly used to enhance hydrogen gas production through metal hydride-catalyzed hydrolysis. These nanoparticles can either be pre-formed and embedded in the gel or generated in situ within the gel. For example, nickel nanoparticles can be produced directly within hydrogels during the reduction of nitrophenols and other nitro compounds. Nanoparticles can also form in hydrogels by soaking them in metal salt solutions and adding a reducing agent, like sodium borohydride or hydrogen gas, to convert the salts into metallic nanoparticles. However, not all catalytic reactions require this reduction step; for instance, 4-vinylpyridine hydrogels can directly form complexes with chromate ions to catalytically oxidize alcohols [102]. These hydrogel-metal systems also show promise for degrading organic dyes, pesticides, and herbicides in environmental applications. Beyond this, hydrogels play supportive roles in catalytic reactions by coating anodes and cathodes to regulate ion flow in electrochemical processes, thereby enhancing reaction efficiency. Enzyme-loaded hydrogels aid in crosslinking, self-healing, and biochemical catalysis [103,104,105]. For example, aptamer-crosslinked polyacrylamide hydrogels have been used to immobilize enzymes on paper substrates, supporting signal amplification in diagnostics. Additionally, in double-network hydrogels, one layer can catalyze the formation of another, broadening their catalytic potential.

6. Conclusions

In conclusion, hydrogels are essential materials in regenerative medicine and smart device applications, showcasing significant potential across various organ systems. Their remarkable properties, such as high-water absorption, biocompatibility, and the ability to mimic native tissue, support cell proliferation and differentiation. Light-sensitive hydrogels are particularly promising, offering applications in drug delivery, microlenses, and biosensors due to their remote and non-invasive activation capabilities. Ongoing research aims to explore diverse hydrogel derivatives and their functionalities, paving the way for the development of novel materials with enhanced properties. Furthermore, tailored modifications and functionalizations can improve hydrogel performance, thereby extending their therapeutic applications and efficacy in tissue regeneration.

However, several challenges must be addressed to fully realize the potential of hydrogels in biomedical and supercapacitor applications. Biocompatibility remains a primary concern, necessitating the development of hydrogels from natural polymers or the modification of synthetic materials to minimize immune responses. Additionally, enhancing mechanical strength is crucial for durable applications, which can be achieved by incorporating reinforcing agents or creating hybrid hydrogels. Stability in biological conditions is vital for effective drug delivery and employing cross-linking or controlled degradation techniques can improve performance. Furthermore, optimizing the release of therapeutic agents requires precise tuning of hydrogel structures. The integration of AI technology in hydrogel-based biosensors can enhance screening and optimization processes. As research advances, hydrogels will continue to play a critical role in both biomedical and energy storage innovations.

Author Contributions

Conceptualization, A.S.P. and R.A.; methodology, K.K.; formal analysis, V.R.B.; investigation, A.S.P.; resources, I.R.; data curation, I.R.; writing—original draft preparation, A.S.P.; writing—review and editing, R.A. and K.K.; visualization, K.S.; supervision, R.P. All authors have read and agreed to the published version of the manuscript.

Data Availability Statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the first/corresponding author.

Acknowledgments

Aepuru gratefully acknowledges the financial support given by the Agencia Nacional de Investigación y Desarrollo (ANID) within the project FONDECYT INICIACIÓN N° 11240484, Chile. Karthik Kannan acknowledges the National Science and Technology Council (NSTC), Taiwan for their support under grant NSTC 113–2811-E-194–004.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

PEG	polyethylene glycol
PVA	polyvinyl alcohol
PAAm	polyacrylamide
PAA	poly(acrylic acid)
LAF	long amyloid fibrils
SAF	impacts of short
WPI	whey protein isolate
SA	sodium alginate
TSM	tamarind seed mucilage
AlgMA	alginate methacryloy
S-Alg	single-crosslinked alginate hydrogel
D-Alg	double-crosslinked alginate hydrogel
TEM	Transmission Electron Microscope
FE-SEM	Field Effect Scanning Electron Microscope
ESEM	Environmental Scanning Electron Microscope
FTIR	Fourier Transform Infrared spectroscopy
CHT	Chitosan
CMC	Carboxymethyl cellulose
MTG	Microbial transglutaminase
OGEP	oxidized Gastrodia elata polysaccharide
GAS	Gastrodin
GAS/CS	Gastrodin-chitosan compound
EGCG	Epigallocatechin gallate
SCL	Soft contact lenses
IOL	Intraocular lenses
ECM	Extracellular matrix
MWCNT	Multiwall carbon nanotubes
MWCNT-CS	multiwall carbon nanotubes–chitosan
PDIV	P (DAAm-co-IA-co-VMA)

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Figures and Table

Figure 1. Hydrogel preparation methods.

Figure 2. Flow chart of affected parameters of hydrogel preparation methods.

Figure 3. (a) The swelling ratio of PDIV1-PDIV4 hydrogel in deionized water, (b) Values of equilibrium swelling ratio for PDIV1-PDIV4 hydrogel in various thermal conditions, (c) swelling-shrinking reversible curves of PDIV1-PDIV4 hydrogels at 37 °C and 25 °C, (d) Values of equilibrium swelling ratio for PDIV1-PDIV4 hydrogel in various pH solutions, (e) swelling-shrinking reversible curves of PDIV1-PDIV4 hydrogels at pH = 1.2 and pH = 7.4 [38].

Figure 4. (a) SEM images of natural and enzyme-induced hydrogels [40]. (b,c) SEM images of SAF- and LAF-WPI hydrogel composites at various concentrations of NaCl with (b) ×40,000 and (c) ×10,000 magnifications. The NaCl concentration (mM) has been specified on the top of the images. Scale bars correspond to 100 nm and 1 μm for parts (b) and (c), respectively [41].

Figure 5. SEM images of external and cross-sectional aspect of the different hydrogel beads. (a,d) SA; (b,e) B1; (c,f) B2 [42].

Figure 6. Tensile (a) and compression (b) stress-strain curves of S—Alg and D—Alg. (c) Oscillatory amplitude sweep of S—Alg and D—Alg. (d) Oscillatory frequency sweep of S—Alg and D—Alg [44].

Figure 7. (a) PVA/CMC hydrogel hanging weight, twisting, knotting, stretching performance. (b) PVA/CMC hydrogel film stretching, poking performance. (c) PVA/CMC hydrogel block poking performance [45]. (d) Tensile stress–strain curves of PVA-CMC (H2O/DMSO) hydrogels, pure PVA (H2O/DMSO) hydrogels and pure PVA (H2O) hydrogels. (e) Freeze moulding of CMC and PVA chains. (f) Continuous loading–unloading curves of PVA-CMC hydrogels with different strains [45]. (g) Cyclic loading–unloading, (h) residual strain and (i) dissipated energy tests of PVA-CMC hydrogel and pure PVA hydrogels [45]. SEM images of Ag-CMC conductive hydrogel at magnifications of (j1) 500×, (j2) 2.5 k × and (j3) 40.56 k× [45]. (k) XRD of PVA/CMC hydrogel and Ag-CMC conductive hydrogel. (l1) Cross sections of Ag-CMC conductive hydrogels and corresponding (l2) [45]. (m) Shore hardness of pure PVA and PVA-CMC hydrogel before and after silver reduction. (n) Tensile stress-strain curve of conductive hydrogel with varying concentrations of AgNO3 and VC concentration of 0.08 M. (o) Tensile stress–strain curve of conductive hydrogel with varying VC concentrations and AgNO3 concentration of 1.0 M [45].

Figure 7. (a) PVA/CMC hydrogel hanging weight, twisting, knotting, stretching performance. (b) PVA/CMC hydrogel film stretching, poking performance. (c) PVA/CMC hydrogel block poking performance [45]. (d) Tensile stress–strain curves of PVA-CMC (H2O/DMSO) hydrogels, pure PVA (H2O/DMSO) hydrogels and pure PVA (H2O) hydrogels. (e) Freeze moulding of CMC and PVA chains. (f) Continuous loading–unloading curves of PVA-CMC hydrogels with different strains [45]. (g) Cyclic loading–unloading, (h) residual strain and (i) dissipated energy tests of PVA-CMC hydrogel and pure PVA hydrogels [45]. SEM images of Ag-CMC conductive hydrogel at magnifications of (j1) 500×, (j2) 2.5 k × and (j3) 40.56 k× [45]. (k) XRD of PVA/CMC hydrogel and Ag-CMC conductive hydrogel. (l1) Cross sections of Ag-CMC conductive hydrogels and corresponding (l2) [45]. (m) Shore hardness of pure PVA and PVA-CMC hydrogel before and after silver reduction. (n) Tensile stress-strain curve of conductive hydrogel with varying concentrations of AgNO3 and VC concentration of 0.08 M. (o) Tensile stress–strain curve of conductive hydrogel with varying VC concentrations and AgNO3 concentration of 1.0 M [45].

Figure 8. (a,b) SEM images of composite hydrogel, (c,d) TEM images of composite hydrogel [48].

Figure 9. (i) FTIR spectra of (a) chitosan, (b) starch, (c) chitosan—starch hydrogel, (d) cefixime drug, and (e) cefixime loaded hydrogel. (ii) FTIR spectra of chitosan/alginate hydrogels [50].

Figure 10. Inhibition zone diameter in the antibacterial study at 37 °C for the developed hydrogels [53].

Figure 11. (a) Demonstration of the antibacterial effect of PVA/PA/GL hydrogel on Escherichia coli and Bacillus subtilis; (b) comparison of growth curves of hydrogels in Escherichia coli; (c) comparison of growth curves of hydrogels in Bacillus subtilis; (d) demonstration of the diameter of the circle of inhibition of PVA/GL hydrogel and PVA/PA/GL hydrogel; (e) stability of PVA/PA/GL hydrogels for 7 day bacterial inhibition in Escherichia coli; (f) stability of PVA/PA/GL hydrogels for 7 day bacterial inhibition in Bacillus cereus [54].

Figure 12. Schematic illustration of EGCG@GEL/GAS/CS-OGEP hydrogel prepared and applied to diabetic wound healing [64].

Figure 13. Electrofabrication of chitosan-based hydrogel contact lenses [73].

Figure 14. Schematic illustration of approaches to make injectable hydrogels for cartilage and bone tissue engineering applications [81].

Figure 15. (i) Stages of the 3 D bioprinting process, (ii) the printability of 3 D printing hydrogel scaffold. (a) The digital model of the 3D scaffold, (b) the outline of the first layer of hydrogel scaffold shape after filled the blank area (c) (the filling rate is 100%), (d) three views of the printed hydrogel scaffold from three different angles (the structure has 30 layers and the height is 15 mm; the fidelity of the top surface is about 80%) [92].

Figure 16. (i) Electrochemical performance of PANi—NF hydrogel symmetric supercapacitors in a 1 M H2SO4 electrolyte; (A) Schematic diagram for PANi-NF hydrogel in a two-electrode system, (B) CV curves at different scan rates, (C) charge/discharge curves at different current densities, and (D) gravimetric and areal capacitances calculated under different current densities. (ii) (a) GCD of the antifreezing supercapacitor for different current densities at −20 °C, (b) CV curves of antifreezing supercapacitors for various scan rates at −20 °C, (c) GCD of single device and three devices combined in series at −20 °C, and the inset shows practical application picture of antifreezing supercapacitor; (d) CV curves at −20 °C and under different deformations; (e) cyclic stability of the antifreezing supercapacitor at −20 °C; (f) photograph of a watch lighted by the device in series and as part of watch band at −27 °C, and −25 °C [101].

References

1. Bhattarai, N.; Gunn, J.; Zhang, M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv. Drug Deliv. Rev.; 2010; 62, pp. 83-99. [DOI: https://dx.doi.org/10.1016/j.addr.2009.07.019] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19799949]

2. Chen, G.; Kawazoe, N. Polymeric and Biomimetic ECM Scaffolds for Tissue Engineering. Polymeric Biomaterials for Tissue Regeneration; Gao, C. Springer: Singapore, 2016; pp. 41-56. [DOI: https://dx.doi.org/10.1007/978-981-10-2293-7_2]

3. Chen, G.; Kawazoe, N. Preparation of Polymer Scaffolds by Ice Particulate Method for Tissue Engineering. Biomaterials Nanoarchitectonics; William Andrew Publishing: Norwich, NY, USA, 2016; pp. 77-95. [DOI: https://dx.doi.org/10.1016/B978-0-323-37127-8.00006-6]

4. Gao, D.; Xu, H.; Philbert, M.A.; Kopelman, R. Bioeliminable nanohydrogels for drug delivery. Nano Lett.; 2008; 8, pp. 3320-3324. [DOI: https://dx.doi.org/10.1021/nl8017274] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18788823]

5. Deligkaris, K.; Tadele, S.T.; Olthuis, W.; Berg, A. Hydrogel-based devices for biomedical applications. Sens. Actuators B Chem.; 2010; 147, pp. 765-774. [DOI: https://dx.doi.org/10.1016/j.snb.2010.03.083]

6. Yue, K.; Trujillo-de Santiago, G.; Alvarez, M.M.; Tamayol, A.; Annabi, N.; Khademhosseini, A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials; 2015; 73, pp. 254-271. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2015.08.045]

7. Hoorick, J.V.; Tytgat, L.; Dobos, A.; Ottevaere, H.; Erps, V.J.; Thienpont, H.; Ovsianikov, A.; Dubruel, P.; Vlierberghe, V.S. (Photo-) cross-linkable gelatin derivatives for biofabrication applications. Acta Biomater.; 2019; 97, pp. 46-73. [DOI: https://dx.doi.org/10.1016/j.actbio.2019.07.035]

8. Ahmed, E.M. Hydrogel: Preparation, characterization, and applications: A review. J. Adv. Res.; 2015; 6, pp. 105-121. [DOI: https://dx.doi.org/10.1016/j.jare.2013.07.006]

9. Ratner, B.D.; Hoffman, A.S. Hydrogels for Medical and Related Applications; American Chemical Society: Washington, DC, USA, 1976; 31. [DOI: https://dx.doi.org/10.1021/bk-1976-0031]

10. Nie, J.; Pei, B.; Wang, Z.; Hu, Q. Construction of ordered structure in polysaccharide hydrogel: A review. Carbohydr. Polym.; 2019; 205, pp. 225-235. [DOI: https://dx.doi.org/10.1016/j.carbpol.2018.10.033]

11. Siepmann, J.; Siegel, R.A.; Rathbone, M.J. Fundamentals and Applications of Controlled Release Drug Delivery; Springer Science & Business Media: Berlin/Heidelberg, Germany, 2011; [DOI: https://dx.doi.org/10.1007/978-1-4614-0881-9]

12. Miyata, T.; Uragami, T.; Nakamae, K. Biomolecule-sensitive hydrogels. Adv. Drug Deliv. Rev.; 2002; 54, pp. 79-98. [DOI: https://dx.doi.org/10.1016/S0169-409X(01)00241-1]

13. Peppas, N.A.; Hilt, J.Z.; Khademhosseini, A.; Langer, R. Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv. Mater.; 2006; 18, 1345. [DOI: https://dx.doi.org/10.1002/adma.200501612]

14. Kausar, A. Nanocarbon in Polymeric Nanocomposites Hydrogel-Design and Multi-Functional Tendencies. Polym.-Plast. Technol. Mater.; 2020; 59, pp. 1505-1521. [DOI: https://dx.doi.org/10.1080/25740881.2020.1757106]

15. Bahram, M.; Mohseni, N.; Moghtader, M. Emerging Concepts in Analysis and Applications of Hydrogels; Majee, S.B. IntechOpen: London, UK, 2016; 266. [DOI: https://dx.doi.org/10.5772/61692]

16. Ma, N.; Lin, H.; Ning, L.; Ji, X.; Wang, F. Temperature and pH-dependent nanogel forsmart pesticide delivery with enhanced foliar dispersion and washout resistancecan effectively control multiple plant diseases. J. Clean. Prod.; 2023; 429, pp. 139536-139545. [DOI: https://dx.doi.org/10.1016/j.jclepro.2023.139536]

17. Dong, J.; Han, A.; Zhao, Y.; Li, H.; Yang, Y.; Yuan, B.; Wang, Y. Smart, degradable, and eco-friendly carboxymethyl cellulose-caii hydrogel-like networks gated MIL-101(FeIII) nanoherbicides for paraquat delivery. Sci. Total Environ.; 2023; 903, 166424. [DOI: https://dx.doi.org/10.1016/j.scitotenv.2023.166424] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37634715]

18. Zhang, Q.; Yu, G.; Zhou, Q.; Li, J.; Feng, Y.; Wang, L.; Tang, Y.; Peng, Y. Eco-friendlyinterpenetrating network hydrogels integrated with natural soil colloid as a greenand sustainable modifier for slow release of agrochemicals. J. Clean. Prod.; 2020; 269, 122060. [DOI: https://dx.doi.org/10.1016/j.jclepro.2020.122060]

19. Lapointe, M.; Barbeau, B. Understanding the roles and characterizing the intrinsicproperties of synthetic vs. natural polymers to improve clarification throughinterparticle bridging: A review. Sep. Purif. Technol.; 2020; 231, 115893. [DOI: https://dx.doi.org/10.1016/j.seppur.2019.115893]

20. Xu, S.; Wu, R.; Huang, X.; Cao, L.; Wang, J. Effect of the anionic-group/cationicgroupratio on the swelling behavior and controlled release of agrochemicals ofthe amphoteric, superabsorbent polymer poly(acrylic acid-codiallyldimethylammoniumchloride). J. Appl. Polym. Sci.; 2006; 102, pp. 986-991. [DOI: https://dx.doi.org/10.1002/app.23990]

21. Lin, J.; Zheng, S.Y.; Xiao, R.; Yin, J.; Wu, Z.L.; Zheng, Q.; Qian, J. Constitutive behaviours of tough physical hydrogels with dynamic metal-coordinated bonds. J. Mech. Phys. Solids; 2020; 139, 103935. [DOI: https://dx.doi.org/10.1016/j.jmps.2020.103935]

22. Kozicki, M.; Kolodziejczyk, M.; Szynkowska, M.; Pawlaczyk, A.; Lesniewska, E.; Matusiak, A.; Adamus, A.; Karolczak, A. Hydrogels made from chitosan and silver nitrate. Carbohydr. Plym.; 2016; 140, pp. 74-87. [DOI: https://dx.doi.org/10.1016/j.carbpol.2015.12.017]

23. Ryu, J.H.; Lee, Y.; Kong, W.H.; Kim, T.G.; Park, T.G.; Lee, H. Catechol functionalized chitosan/pluronic hydrogels for tissue adhesives and hemostatic materials. Biomacromolecules; 2019; 12, pp. 2653-2659. [DOI: https://dx.doi.org/10.1021/bm200464x]

24. Wang, T.; Chen, L.; Shen, T.; Wu, D. Preparation and properties of a novel thermos-sensitive hydrogel based on chitosan/hydroxypropyl methylcellulose/glycerol. Int. J. Biol. Macromol.; 2016; 93, pp. 775-782. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2016.09.038]

25. Pan, X.; Li, Y.; Pang, W.; Xue, Y.; Wang, Z.; Jiang, C.; Shen, C.; Liu, Q.; Liu, L. Preparation, characterisation and comparison of glabridin loaded hydrogel forming microneedles by chemical and physical cross-linking. Int. J. Pharm.; 2022; 617, 121612. [DOI: https://dx.doi.org/10.1016/j.ijpharm.2022.121612]

26. Wang, W.; Bai, H.; Zhao, Y.; Kang, S.; Yi, H.; Zhang, T.; Song, S. Synthesis of chitosan cross linked 3D network structured hydrogel for methylene blue removal. Int. J. Bio. Macromol.; 2019; 14, pp. 98-107. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2019.08.225] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31473311]

27. Y-Tov, O.; Seliktar, D.; B-Peled, H. PEG-Thiol based hydrogels with controllable properties. Eur. Polym. J.; 2016; 74, pp. 1-12. [DOI: https://dx.doi.org/10.1016/j.eurpolymj.2015.11.002]

28. Sun, X.F.; Xie, Y.; Shan, S.; Li, W.; Sun, L. Chemically crosslinked xylan/Graphene oxide composite hydrogel for copper ions removal. J. Polym. Environ.; 2022; 30, pp. 3999-4013. [DOI: https://dx.doi.org/10.1007/s10924-022-02475-5]

29. Rahnama, H.; Khorasani, S.N.; Aminoroaya, A.; Molavian, M.R.; Allafchian, A.; Kahalili, S. Facile preparation of chitosan dopamine inulin aldehyde hydrogel for drug delivery application. Int. J. Biol. Macromol.; 2021; 185, pp. 716-724. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2021.06.199] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34217742]

30. Wu, Y.; Liu, T.; Shi, Y.; Wang, H. Dramatically enhancing mechanical properties of hydrogels by drying reactive polymers at elevated temperatures to introduce strong physical and chemical crosslinks. Polymer; 2022; 249, 124842. [DOI: https://dx.doi.org/10.1016/j.polymer.2022.124842]

31. Nguyen, N.T.P.; Nguyen, L.V.H.; Thanh, N.T.; Van Toi, V.; Quyen, T.N.; Tran, P.A.; Wang, H.M.D.; Nguyen, T.H. Stabilization of silver nanoparticles in chitosan and gelatin hydrogel and its applications. Matter. Lett.; 2019; 248, pp. 241-245. [DOI: https://dx.doi.org/10.1016/j.matlet.2019.03.103]

32. Singh, B.; Singh, B. Modification of sterculia gum polysaccharide via network formation by radiation induced crosslinking polymerization for biomedical applications. Int. J. Biol. Macromol.; 2018; 116, pp. 91-99. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2018.05.032]

33. Tan, H.; Chu, C.R.; Payne, K.A.; Marra, K.G. Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering. Biomaterials; 2009; 30, pp. 2499-2506. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2008.12.080]

34. Ito, T.; Yeo, T.; Highley, C.B.; Bellas, E.; Kohane, D.S. Dextran-based in situ cross-linked injectable hydrogels to prevent peritoneal adhesions. Biomaterials; 2007; 28, pp. 3418-3426. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2007.04.017]

35. Ono, K.; Saito, Y.; Yura, H.; Ishikawa, K.; Kurita, A.; Akaike, T.; Ishihara, M. Photocrosslinkable chitosan as a biological adhesive. J. Biomed. Mater. Res.; 2000; 49, pp. 289-295. [DOI: https://dx.doi.org/10.1002/(SICI)1097-4636(200002)49:2<289::AID-JBM18>3.0.CO;2-M]

36. Yoo, H.S. Photo-cross-linkable and thermo-responsive hydrogels containing chitosan and Pluronic for sustained release of human growth hormone. J. Biomater. Sci. Polym. Ed.; 2007; 18, pp. 1429-1441. [DOI: https://dx.doi.org/10.1163/156856207782246803] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17961325]

37. Ben Ammar, N.E.; Barbouche, M.; Hamzaoui, A.H. Hydrogels Based on Natural Polymers; Chen, Y. Elsevier: Cambridge, MA, USA, 2020; pp. 3-16. [DOI: https://dx.doi.org/10.1016/B978-0-12-816421-1.00001-X]

38. Li, Q.; Ma, W.; Ma, H.; Liu, H.; Shang, H.; Qiao, N.; Sun, X. pH-responsive biomass-based hydrogels for 5-fu delivery: Investigating the influential role of itaconic acid content on structural characteristic, swelling behaviour, and drug loading capacity. Mater. Chem. Phy.; 2024; 322, 129604. [DOI: https://dx.doi.org/10.1016/j.matchemphys.2024.129604]

39. Peppas, N.A.; Keys, K.B.; Torres-Lugo, M.; Lowman, A.M. Poly (ethylene glycol)-containing hydrogels in drug delivery. J. Control Release; 1999; 62, 81. [DOI: https://dx.doi.org/10.1016/S0168-3659(99)00027-9] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10518639]

40. Zhang, Z.; Long, M.; Zheng, N.; Deng, Y.; Wang, Q.; Osire, T.; Xia, X. Microstructural, physicochemical properties, and interaction mechanism of hydrogel nanoparticles modified by high catalytic activity transglutaminase crosslinking. Food Hydrocoll.; 2024; 147, 109384. [DOI: https://dx.doi.org/10.1016/j.foodhyd.2023.109384]

41. Khalesi, H.; Zhai, Y.; Sun, C.; Lu, W.; Cao, Y.; Zhang, Y.; Kadkhodaee, R.; Fang, Y. Influence of amyloid fibril length and ionic strength on WPI-based fiber-hydrogel composites: Microstructural, rheological and water holding properties. Food Hydrocoll.; 2024; 148, 109499. [DOI: https://dx.doi.org/10.1016/j.foodhyd.2023.109499]

42. Camargo, C.S.; Guerrero, R.A.; Ramirez, A.J.; Reyes, A.E.; Gutierrez, V.K.S.; Alonso, P.C. Microstructural influence on physical properties and release profiles of sesame oil encapsulated into sodium alginate-tamarind mucilage hydrogel beads. Carbohydr. Polym. Tech. Appl.; 2023; 5, 100302.

43. Markovi, G.; Marinovi, M.; Jovanovi, V.C.; Samaržija-Jovanovi, S.; Budinski-Simendic, J. Polymer Science: Research Advances, Practical Applications and Educational Aspects; Formatex Research Center: Badajoz, Spain, 2016; 586.

44. Zhang, W.; Liu, S.; Wang, L.; Li, B.; Xie, M.; Deng, Y.; Zhang, J.; Zeng, H.; Qiu, L.; Huang, L. et al. Triple-crosslinked double-network alginate/dextran/dendrimer hydrogel with tunable mechanical and adhesive properties: A potential candidate for sutureless keratoplasty. Carbohydr. Polym.; 2024; 344, 122538. [DOI: https://dx.doi.org/10.1016/j.carbpol.2024.122538]

45. Hou, Y.; Chang, Y.; Zhao, Z.; Zhang, M.; Zhao, Q.; Guo, M.; Zhao, J.; Wu, S.; Ma, Y. Advanced In-Situ functionalized conductive hydrogels with high mechanical strength for hypersensitive soft strain sensing applications. Chem. Eng. J.; 2024; 497, 154731. [DOI: https://dx.doi.org/10.1016/j.cej.2024.154731]

46. Sharma, R.; Lalhall, A.; Puri, S.; Wangoo, N. Design of Fmoc-phenylalanine nanofibrillar hydrogel and mechanistic studies of its antimicrobial action against bot gram positive and gram negative bacteria. Appl. Bio. Mater.; 2023; 6, pp. 494-506. [DOI: https://dx.doi.org/10.1021/acsabm.2c00767]

47. Raveendran, R.L.; Valsala, M.; Anirudhan, T.S. Development of nanosilver embedded injectable liquid crystalline hydrogel from alginate and chitosan for potent antibacterial and anticancer applications. J. Ind. Eng. Chem.; 2023; 119, pp. 261-273. [DOI: https://dx.doi.org/10.1016/j.jiec.2022.11.044]

48. Huang, H.; Chen, R.; Yang, S.; Li, L.; Liu, Y.; Huang, J. Facile fabrication of MnO₂- embedded 3-D porous polyaniline composite hydrogel for supercapacitor electrode with high loading. High Perform. Polym.; 2020; 32, pp. 286-295. [DOI: https://dx.doi.org/10.1177/0954008319860893]

49. Bouhadir, K.H.; Alsberg, E.; Mooney, D.J. Hydrogel for combination delivery antineoplastic agents. Biomater; 2001; 22, pp. 2625-2633. [DOI: https://dx.doi.org/10.1016/S0142-9612(01)00003-5] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11519782]

50. Sethi, S.; Mahajan, P.; Thakur, S.; Sharma, N.; Singh, N.; Kumar, A.; Kaur, A.; Kaith, B.S. Design and evaluation of fluorescent chitosan-starch hydrogel for drug delivery and sensing applications. Int. J. Bio. Macromol.; 2024; 274, 133486.

51. Enoch, K.; Rakavi, C.S.; Somasundaram, A.A. Tuning the rheological properties of chitosan/alginate hydrogels for tissue engineering application. Coll Surf. Asp.; 2024; 697, 134434. [DOI: https://dx.doi.org/10.1016/j.colsurfa.2024.134434]

52. Gupta, V.; Kannan, K.; Tari, V.; Chandra, N. Bioengineered silver nanoparticles using Brassica oleracea sub sp. botrytis (L.) for enhanced antibacterial activity. Phys. Chem. Solid State; 2024; 25, pp. 303-310. [DOI: https://dx.doi.org/10.15330/pcss.25.2.303-310]

53. Krishna, V.D.; Sankar, R.M.; Sarma, K.G.V.P.; Samundeshwari, L.E. Copper nanoparticles loaded gelatin/polyvinyl alcohol/guar gum-based 3D printable multimaterial hydrogel for tissue engineering applications. Int. J. Bio. Macromol.; 2024; 276, 133866. [DOI: https://dx.doi.org/10.1016/j.ijbiomac.2024.133866]

54. Wan, Z.; Qu, R.; Sun, Y.; Gao, Y.; Gao, G.; Chen, K.; Liu, T. Physically crosslinked polyvinyl alcohol, phytic acid and glycerol hydrogels for wearable sensors with biocompatibility, antimicrobial stability and anti-freezing. Eur. Polym. J.; 2024; 211, 112974. [DOI: https://dx.doi.org/10.1016/j.eurpolymj.2024.112974]

55. da Silva, G.M.; Ferreira, I.L.M.; Costaa, M.P.M.; Rochaa, R.F.P. Physicochemical properties of superabsorbent hydrogels formed by polyelectrolytic complexation of Carboxymethylcellulose-chitosan at basic Ph. J. Braz. Chem. Soc.; 2023; 34, pp. 1236-1249. [DOI: https://dx.doi.org/10.21577/0103-5053.20230035]

56. Tang, J.; Javaid, M.U.; Pan, C.; Yu, G.; Berry, R.M.; Tam, K.C. Self-healing stimuliresponsive cellulose nanocrystal hydrogels. Carbohydr. Polym.; 2020; 229, 115486. [DOI: https://dx.doi.org/10.1016/j.carbpol.2019.115486]

57. Lu, B.; Lin, F.; Jiang, X.; Cheng, J.; Lu, Q.; Song, J.; Chen, C.; Huang, B. One-Pot Assembly of Microfibrillated Cellulose Reinforced PVA− Borax Hydrogels with Self-Healing and pH-Responsive Properties. ACS Sustain. Chem. Eng.; 2017; 5, pp. 948-956. [DOI: https://dx.doi.org/10.1021/acssuschemeng.6b02279]

58. Altunbas, A.; Lee, S.J.; Rajasekaran, S.A.; Schneider, J.P.; Pochan, D.J. Encapsulation of curcumin in self-assembling peptide hydrogels as injectable drug delivery vehicles. Biomater; 2011; 32, pp. 5906-5914. [DOI: https://dx.doi.org/10.1016/j.biomaterials.2011.04.069] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21601921]

59. French, K.M.; Somasuntharam, I.; Davis, M.E. Self-assembling peptide-based delivery of therapeutics for myocardial infarction. Adv. Drug Deliv. Rev.; 2016; 96, pp. 40-53. [DOI: https://dx.doi.org/10.1016/j.addr.2015.04.023] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25959427]

60. Nam, S.; Hu, K.H.; Butte, M.J.; Chaudhuri, O. Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels. Proc. Natl. Acad. Sci. USA; 2016; 113, pp. 5492-5497. [DOI: https://dx.doi.org/10.1073/pnas.1523906113] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27140623]

61. Cacopardo, L.; Guazzelli, N.; Nossa, R.; Mattei, G.; Ahluwalia, A. Engineering hydrogel viscoelasticity. J. Mech. Behav. Biomed. Mater.; 2019; 89, pp. 162-167. [DOI: https://dx.doi.org/10.1016/j.jmbbm.2018.09.031] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30286375]

62. Firlar, I.; Altunbek, M.; McCarthy, C.; Ramalingam, M.; Camci-Unal, G. Functional hydrogels for treatment of chronic wounds. Gels; 2022; 8, 127. [DOI: https://dx.doi.org/10.3390/gels8020127]

63. Fan, F.; Saha, S.; Hanjaya-Putra, D. Biomimetic hydrogels to promote woundhealing. Front. Bioeng. Biotechnol.; 2021; 9, 718377. [DOI: https://dx.doi.org/10.3389/fbioe.2021.718377]

64. Xin, C.; Cheng, Z.; Liu, W.; Li, W.; Zhu, H. The antibacterial and hemostatic activity of Gastrodia elata polysaccharide based hydrogel embedded with drug carrying microspheres accelerates diabetic wound healing. Chem. Eng. J.; 2024; 492, 152403. [DOI: https://dx.doi.org/10.1016/j.cej.2024.152403]

65. Karayilan, M.; Clamen, L.; Becker, M.L. Polymeric materials for eye surface and intraocular applications. Biomacromolecules; 2021; 22, pp. 223-261. [DOI: https://dx.doi.org/10.1021/acs.biomac.0c01525]

66. Aswathy, S.H.; Narendrakumar, U.; Manjubala, I. Commercial hydrogels for biomedical applications. Heliyon; 2020; 6, e03719. [DOI: https://dx.doi.org/10.1016/j.heliyon.2020.e03719]

67. Li, Z.; Li, Z.; Cheng, H.; Ke, L.; Liu, M.; Wang, C.-G.; Loh, X.J.; Wu, Y.-L. Recent advances in new copolymer hydrogel-formed contact lenses for ophthalmic drug delivery. Chem. Nano Mat.; 2021; 7, pp. 564-579. [DOI: https://dx.doi.org/10.1002/cnma.202100008]

68. Moreddu, R.; Vigolo, D.; Yetisen, A.K. Contact Lens technology: From fundamentals to applications. Adv. Healthc. Mater.; 2019; 8, 1900368. [DOI: https://dx.doi.org/10.1002/adhm.201900368] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31183972]

69. Narayanaswamy, R.; Torchilin, V.P. Hydrogels and their applications in targeted drug delivery. Molecules; 2019; 24, 603. [DOI: https://dx.doi.org/10.3390/molecules24030603] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30744011]

70. Cooper, R.C.; Yang, H. Hydrogel-based ocular drug delivery systems: Emerging fabrication strategies, applications, and bench-to-bedside manufacturing considerations. J. Control. Release; 2019; 306, pp. 29-39. [DOI: https://dx.doi.org/10.1016/j.jconrel.2019.05.034] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31128143]

71. Jacob, S.; Nair, A.B.; Shah, J.; Sreeharsha, N.; Gupta, S.; Shinu, P. Emerging role of hydrogels in drug delivery systems, tissue engineering and wound management. Pharmaceutics; 2021; 13, 357. [DOI: https://dx.doi.org/10.3390/pharmaceutics13030357] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33800402]

72. Topete, A.; Pinto, C.A.; Barroso, H.; Saraiva, J.A.; Barahona, I.; Saramago, B.; Serro, A.P. High hydrostatic pressure as sterilization method for drug-loaded intraocular lenses. ACS Biomater. Sci. Eng.; 2020; 6, pp. 4051-4061. [DOI: https://dx.doi.org/10.1021/acsbiomaterials.0c00412]

73. Yang, C.; Wang, M.; Wang, W.; Liu, H.; Deng, H.; Du, Y. Electrodeposition induced covalent cross linking of chitosan for electrofabrication of hydrogel contact lenses. Carbohydr. Polym.; 2022; 292, 119678. [DOI: https://dx.doi.org/10.1016/j.carbpol.2022.119678]

74. Kesharwani, P.; Bisht, A.; Alexander, A.; Dave, V.; Sharma, S. Biomedical applications of hydrogels in drug delivery system: An update. J. Drug Deliv. Sci. Technol.; 2021; 66, 102914. [DOI: https://dx.doi.org/10.1016/j.jddst.2021.102914]

75. Pita-L’opez, M.L.; Fletes-Vargas, G.; Espinosa-Andrews, H.; Rodríguez-Rodríguez, R. Physically cross-linked chitosan-based hydrogels for tissue engineering applications: A state-of-the-art review. Eur. Polym. J.; 2021; 145, 110176. [DOI: https://dx.doi.org/10.1016/j.eurpolymj.2020.110176]

76. Reakasame, S.; Boccaccini, A.R. Oxidized alginate-based hydrogels for tissue engineering applications: A review. Biomacromolecules; 2018; 19, pp. 3-21. [DOI: https://dx.doi.org/10.1021/acs.biomac.7b01331]

77. Gomez-Florit, H.M.; Pardo, A.; Domingues, R.M.A.; Graça, A.L.; Babo, P.S.; Reis, R.L.; Gomes, M.E. Natural-based hydrogels for tissue engineering applications. Molecules; 2020; 25, 5858. [DOI: https://dx.doi.org/10.3390/molecules25245858]

78. Zhao, Y.; Song, S.; Ren, X.; Zhang, J.; Lin, Q.; Zhao, Y. Supramolecular adhesive hydrogels for tissue engineering applications. Chem. Rev.; 2022; 122, pp. 5604-5640. [DOI: https://dx.doi.org/10.1021/acs.chemrev.1c00815] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35023737]

79. Asadi, N.; Alizadeh, E.; Saleh, R.; Khalandi, B.; Davaran, S.; Akbarzadeh, A. Nanocomposite hydrogels for cartilage tissue engineering: A review. Artif Cells Nanomed. Biotechnol.; 2018; 46, pp. 465-471. [DOI: https://dx.doi.org/10.1080/21691401.2017.1345924] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28743188]

80. Huang, J.; Liu, F.; Su, H.; Xiong, J.; Yang, L.; Xia, J.; Liang, Y. Advanced nanocomposite hydrogels for cartilage tissue engineering. Gels; 2022; 8, 138. [DOI: https://dx.doi.org/10.3390/gels8020138] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35200519]

81. Liu, M.; Zeng, X.; Ma, C.; Yi, H.; Ali, Z.; Mou, X.; Li, S.; Deng, Y.; He, N. Injectable hydrogels for cartilage and bone tissue engineering. Bone Res.; 2017; 5, 17014. [DOI: https://dx.doi.org/10.1038/boneres.2017.14] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28584674]

82. Negut, I.; Bita, B. Exploring the potential of artificial intelligence for hydrogel development—A short review. Gels; 2023; 9, 845. [DOI: https://dx.doi.org/10.3390/gels9110845]

83. Habib, A.; Sathish, V.; Mallik, S.; Khoda, B. 3D printability of alginate-Carboxymethyl cellulose hydrogel. Materials; 2018; 11, 454. [DOI: https://dx.doi.org/10.3390/ma11030454]

84. Deo, K.A.; Singh, K.A.; Peak, C.W.; Alge, D.L.; Gaharwar, A.K. Bioprinting 101: Design, fabrication, and evaluation of cell-laden 3D bioprinted scaffolds. Tissue Eng. Part A; 2020; 26, pp. 318-338. [DOI: https://dx.doi.org/10.1089/ten.tea.2019.0298]

85. Chen, X.B.; Anvari-Yazdi, A.F.; Duan, X.; Zimmerling, A.; Gharraei, R.; Sharma, N.K.; Sweilem, S.; Ning, L. Biomaterials/bioinks and extrusion bioprinting. Bioact. Mater.; 2023; 28, pp. 511-536. [DOI: https://dx.doi.org/10.1016/j.bioactmat.2023.06.006]

86. Abdollahiyan, P.; Oroojalian, F.; Mokhtarzadeh, A.; de la Guardia, M. Hydrogel-based 3D bioprinting for bone and cartilage tissue engineering. Biotechnol. J.; 2020; 15, 2000095. [DOI: https://dx.doi.org/10.1002/biot.202000095]

87. Weis, M.; Shan, J.; Kuhlmann, M.; Jungst, T.; Tessmar, J.; Groll, J. Evaluation of hydrogels based on oxidized hyaluronic acid for bioprinting. Gels; 2018; 4, 82. [DOI: https://dx.doi.org/10.3390/gels4040082]

88. Antich, C.; de Vicente, J.; Jim’enez, G.; Chocarro, C.; Carrillo, E.; Montanez, E.; G’alvez-Martín, P.; Marchal, J.A. Bio-inspired hydrogel composed of hyaluronic acid and alginate as a potential bio ink for 3D bioprinting of articular cartilage engineering constructs. Acta Biomater.; 2020; 106, pp. 114-123. [DOI: https://dx.doi.org/10.1016/j.actbio.2020.01.046] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32027992]

89. Boons, R.; Siqueira, G.; Grieder, F.; Kim, S.J.; Giovanoli, D.; Zimmermann, T.; Nystrom, G.; Coulter, F.B.; Studart, A.R. 3D Bioprinting of Diatom-Laden Living Materials for Water Quality Assessment. Small; 2023; 19, pp. 2033771-2033783. [DOI: https://dx.doi.org/10.1002/smll.202300771] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/37691091]

90. Ome, R.; Mohsin, M.Z.; Mohsin, A.; Mushtaq, B.S.; Huang, X.; Guo, M.; Zhuang, Y.; Huang, J. Engineered Bacteria-Based Living Materials for Biotherapeutic Applications. Front. Bioeng. Biotechnol.; 2022; 10, pp. 870675-870689. [DOI: https://dx.doi.org/10.3389/fbioe.2022.870675]

91. Lima, T.D.P.; Canelas, C.A.D.A.; Concha Viktor, O.C.; da Costa, F.A.M.; Passos, M.F. 3D Bioprinting Technology and Hydrogels Used in the Process. J. Funct. Mater.; 2022; 13, 214. [DOI: https://dx.doi.org/10.3390/jfb13040214]

92. He, Y.; Yang, F.F.; Zhao, H.M.; Gao, Q.; Xia, B.; Fu, J.Z. Research on the printability of hydrogels in 3D bioprinting. Sci. Rep.; 2016; 6, 29977. [DOI: https://dx.doi.org/10.1038/srep29977]

93. Diaconu, M.; Litescu, S.C.; Radu, G.L. Laccase MWCNT-chitosan biosensor-A new tool for total polyphenolic content evaluation from in vitro cultivated plants. Sens. Actuators B; 2010; 145, pp. 800-806. [DOI: https://dx.doi.org/10.1016/j.snb.2010.01.064]

94. Zaninia, V.P.; de Mishimaa, B.L.; Solis, V. Anamperometric biosensor based on lactate oxidase immobilized in laponite-chitosan hydrogel on a glassy carbon electrode. Application to the analysis of l-lactate in food samples. Sens. Actuators B; 2011; 155, pp. 75-80. [DOI: https://dx.doi.org/10.1016/j.snb.2010.11.026]

95. Xu, Y.; Lin, Z.; Huang, X.; Liu, Y.; Huang, Y.; Duan, X. Flexible solid-state supercapacitors based on three-dimensional graphene hydrogel films. ACS Nano; 2013; 7, pp. 4042-4049. [DOI: https://dx.doi.org/10.1021/nn4000836]

96. Chinnaiah, K.; Kannan, K.; Palko, N.; Maria, G.; Guganathan, L.; Gurushankar, K. Bioengineered Ag/NiO nanocomposites as advanced battery-supercapacitor electrodes for highly efficient symmetric hybrid devices. Ionics; 2024; 30, pp. 1691-1707. [DOI: https://dx.doi.org/10.1007/s11581-023-05361-9]

97. Chinnaiah, K.; Kannan, K.; Palko, N.; Maria, G.; Chen, Y.-S.; Gurushankar, K. Exploring the potential of Withania somnifera-mediated Ag/Mn₃O₄ nanocomposites as electrode material for high-performance supercapattery device. J. Taiwan Inst. Chem. Eng.; 2024; 157, 105441. [DOI: https://dx.doi.org/10.1016/j.jtice.2024.105441]

98. Kannan, K.; Chinnaiah, K.; Gurushankar, K.; Krishnamoorthi, R.; Chen, Y.-S.; Murphin Kumar, P.S.; Li, Y.-Y. Investigation of the Electrochemical Behavior of CuO-NiO-Co₃O₄ Nanocomposites for Enhanced Supercapacitor Applications. Materials; 2024; 17, 3976. [DOI: https://dx.doi.org/10.3390/ma17163976] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/39203154]

99. Chen, P.; Yang, J.J.; Li, S.S.; Wang, Z.; Xiao, T.Y.; Qian, Y.H.; Yu, S.H. Hydrothermal synthesis of macroscopic nitrogen-doped graphene hydrogels for ultrafast supercapacitor. Nano Energy; 2013; 2, pp. 249-256. [DOI: https://dx.doi.org/10.1016/j.nanoen.2012.09.003]

100. Moussa, M.; El-Kady, M.F.; Dubal, D.; Tung, T.T.; Nine, M.J.; Mohamed, N.; Kaner, R.B.; Losic, D. Self-Assembly and Cross-Linking of Conducting Polymers into 3D Hydrogel Electrodes for Supercapacitor Applications. ACS Appl. Energy Mater.; 2020; 3, pp. 923-932. [DOI: https://dx.doi.org/10.1021/acsaem.9b02007]

101. Xu, T.; Yang, D.; Zhang, S.; Zhao, T.; Zhang, M.; Yu, Z.-Z. Antifreezing and stretchable all-gel-state supercapacitor with enhanced capacitances established by graphene/PEDOT-polyvinyl alcohol hydrogel fibers with dual networks. Carbon; 2021; 171, pp. 201-210. [DOI: https://dx.doi.org/10.1016/j.carbon.2020.08.071]

102. Sahiner, N.; Ozay, O.; Aktas, N.; Inger, E.; He, J. The on-demand generation of hydrogen from Co-Ni bimetallic nano catalyst prepared by dual use of hydrogel: As template and as reactor. Int. J. Hydrog. Energy.; 2011; 36, pp. 15250-15258. [DOI: https://dx.doi.org/10.1016/j.ijhydene.2011.08.082]

103. Surendran, P.; Lakshmanan, A.; Priya, S.S.; Balakrishnan, K.; Rameshkumar, P.; Kannan, K.; Mahalakshmi, K.; Gayathri, V.; Vinitha, G. Synthesis of fluorescent carbon quantum dots from Manihot esculenta waste peels for nonlinear optical and biological applications. Chem. Phys. Impact; 2024; 8, 100515. [DOI: https://dx.doi.org/10.1016/j.chphi.2024.100515]

104. Zhang, X.; Xu, J.; Lang, C.; Qiao, S.; An, G.; Fan, X.; Zhao, L.; Hou, C.; Liu, J. Enzyme-regulated fast self-healing of a pillararene-based hydrogel. Biomacromolecules; 2017; 18, pp. 1885-1892. [DOI: https://dx.doi.org/10.1021/acs.biomac.7b00321]

105. Wang, H.; Gu, H.; Chen, Z.; Shang, L.; Zhao, Z.; Gu, Z.; Zhao, Y. Enzymatic inverse opal hydrogel particles for biocatalyst. ACS Appl. Mater. Interfaces; 2017; 9, pp. 12914-12918. [DOI: https://dx.doi.org/10.1021/acsami.7b01866]