Lignin is a potential initiator molecule for the hydrogel synthesis and has several biological applications, such as tissue engineering and wound treatment, since it is less toxic and biocompatible [15].

The degradation of lignin is caused by certain fungi and bacteria. In nature, it is mainly broken down by fungi, which are more effective than bacteria, which tend to be slower and less extensive. These microorganisms rely on specialized enzyme systems that degrade lignin through radical-based oxidative processes. They can produce a variety of enzymes (including different isoenzymes and isoforms) depending on environmental conditions such as nutrient supply, oxygen levels, and temperature, which helps in the effective breakdown of lignin into biomass [7]. Denser pore architectures created by highly crosslinked hydrogels make them less accessible to microorganisms that break down lignin, such as actinomycetes and fungi. Fungal attack is further limited by reducing phenolic substructures because many fungi depend on enzymes that target these groups [26].

Although research on bacterial lignin degradation is more limited compared to fungi, certain bacteria are known to degrade lignin, mainly belonging to actinomycetes, α-proteobacteria, and γ-proteobacteria groups [27].

Lignin shows good biocompatibility when combined with many polymers such as chitosan, polyethylene glycol (PEG), collagen, etc., making it useful for biomedical applications like drug delivery and tissue engineering. In many studies, lignin-based composites have shown minimal cytotoxicity and good cell viability, indicating that lignin is a safe and effective component. This has been demonstrated by Ravishankar and coworkers [28], they prepared hydrogel and cross-linked films by mixing chitosan solution with alkali lignin solution. The MTT assay results suggest that the gels showed low cytotoxicity with cell viability of 99 ± 3% for chitosan-alkali lignin xerogels comparable to pure chitosan (99 ± 2%) and alkali lignin (114 ± 0.2%), confirming good biocompatibility [28]. In another study, Li and team [29] prepared lignin amine (LA) by modifying sodium lignosulfonate and then developed LA- PVA (lignin amine-poly vinyl alcohol) hydrogel. The cytotoxicity testing using L929 cells (CCK-8 assay) showed that cells proliferated well in the presence of hydrogel. Although cell viability decreased by about 25% compared to control, it was still considered low, indicating acceptable biocompatibility with maintained bacterial activity [29].

Organosolv lignin shows the best biocompatibility because it contains very low sulfur and fewer impurities, making it more suitable for biomedical hydrogels. Purified kraft lignin can also be used but may contain residual sulfur. Lignosulfonates are generally less preferred due to their higher sulfur content and ionic nature. Biocompatibility must always be confirmed with specific in-vitro (Cytotoxicity assay) and in-vivo studies to ensure safety, cell compatibility, and predictable biological response [7].

The content of the lignin-based hydrogel directly affects its mechanical properties, including tensile strength, rheological properties, storage modulus, and loss modulus. An increase in the content of lignin may result in a higher degree of crossing as well as the storage and loss modulus, which indicate energy dissipation and stiffness of the hydrogel, and so will the tensile strength [15].

The mechanical properties of lignin-based hydrogels depend mainly on the type and amount of crosslinking in their three-dimensional network. If the network is formed by weak particle attractions, it is unstable and easily damaged. Hydrogen-bonded networks are more stable and elastic due to higher liquid content and particular and partial molecular alignment. The strongest and most stable hydrogels are formed through chemical (covalent) bonds, making them suitable for mechanical and thermal applications. For instance, Belgodere and team [30] developed collagen-based 3D hydrogels combined with lignin materials, specifically sodium lignosulfonate (SLS) and alkali-extracted lignin, to enhance the mechanical properties and functionality of the collagen matrices. SLS significantly increases stiffness by strongly interacting with collagen fibres. Transmission Electron Microscopy (TEM) showed that collagen-SLS fibril bundles exhibited a tighter and more compact structure than collagen-only fibril bundles. This indicates that specific chemical structure and interactions of lignin, rather than just its presence, are crucial for enhancing stiffness in a collagen-based composite [30].

Lignin content plays a key role in mechanical performance. Increasing lignin improves rheological properties, including storage modulus (G’) and loss modulus (G”), with G’ generally higher due to the rigid phase within the hydrogel, which further enhances mechanical strength [26].

Additionally, the tensile strength of lignin-based hydrogels can vary from 0.5 to 4 MPa according to the type of lignin and its cross-linking density. In comparison, tensile strength of conventional chitosan hydrogels ranges between 0.1 and 2 MPa, while alginate systems often remain below 1 MPa [31].

The hydrophilic network structure of lignin- based hydrogels is due to the presence of hydrophilic groups, such as hydroxyl, amino, carboxyl, and sulfonate functional groups in lignin, that form strong connections with water molecules, which allow these systems to absorb and hold large volumes of water. Additionally, the greater swelling ratios are associated with a less dense pore size distribution. This has been observed in a hydrogel prepared by Mondal et al. [32], using SL, polyacrylic acid (PAA), and NiCl₂. Results suggested that water retention is strongly enhanced by SL due to its hydrophilic functional groups and network-forming ability. SL contains phenolic hydroxyl and sulfonate groups, which can form H-bonds with water molecules and hold water within the hydrogel matrix. Also, lignin forms crosslinking (via H-bonding and coordination with Ni²⁺), creating a dense and compact polymer network that physically restricts water evaporation. Additionally, the charged sulfonate groups attract and stabilize water through electrostatic interaction, reducing water loss [32].

Moreover, the type and density of crosslinking determine the amount of water absorbed, as physical crosslinks enable more responsive action, while chemical crosslinks improve structural integrity and prolonged swelling. Their characteristic of responding to external stimuli like temperature, pH, and ionic strength makes them useful for regulated water retention. Hence, they are excellent options for use in biomedical domains, personal care goods, and agriculture, where moisture control is essential [26, 33]. The moderate swelling of the lignin system is attributed to π–π interactions and hydrogen bonding within the polymer network, which restricts excessive water uptake while maintaining structural integrity [34].

Lignin is a complex aromatic polymer made of H, G, and S units with various linkages and functional groups that generate chromophore (unsaturated group responsible for electron absorption) such as quinoids, catechols, conjugated carbonyls and auxochromes (saturated groups with nonbonding electrons) such as phenolic hydroxyl, methoxy, amino, –CO, –SH, and –SCH₃ groups that enhance UV absorption by donating electrons to the aromatic ring of chromophore. These structures absorb UV light through electronic transitions, giving lignin excellent UV-shielding properties. However, its practical use is limited by its dark color, which reduces its aesthetic and commercial value [20, 35]. This has been demonstrated by Li and team [36], who developed lignin-based model compounds and incorporated them into sunscreen formulations to systematically study UV-shielding behaviour and synergy with ethylhexyl methoxycinnamate (EHMC). Lignin enhances UV protection due to the chromophore groups (C=C, carbonyl, quinone) that absorb UV radiation through π→π and n→π electronic transitions. While auxochromes increase electron density and reduce the HOMO-LUMO energy gap, resulting in stronger and red-shifted absorption in the UVA-UVB region. Lignin exhibits a synergistic effect with EHMC through π–π stacking interactions, forming charge-transfer complexes that further lower the energy gap and increase absorption intensity and SPF [36].

The pore structure plays a crucial role in controlling the diffusion, absorption, and release characteristics of active ingredients such as drugs, proteins, and nanoparticles in lignin-based hydrogels. The accessibility and mobility of these entities within the hydrogel system are determined by the mesh size (ξ) of the lignin-based hydrogel, which refers to the average distance between cross-linked polymer chains. Typically, lignin-based hydrogels exhibit a rougher surface morphology. Compact pores are observed in hydrogels containing up to 5% (w/w) lignin, whereas lignin concentrations above 5% (w/w) result in larger, more irregular pores and defects in the hydrogel texture [26].

Lignin can be combined with polymers such as PVA, PEG, or acrylic acid to achieve variable crosslinking densities, owing to its complex aromatic structure and abundance of functional groups (hydroxyl, carboxyl, and methoxyl). Consequently, the network mesh size can be tuned from nanometres to micrometres, depending on the degree of swelling and the crosslinking technique employed [37].

Zerpa and team prepared lignin-based hydrogels via free radical polymerization using a fixed lignin content (7–10% w/w) with varying amounts of NIPAAM, and MBAAm with AIBN as an initiator. The incorporation of lignin significantly reduced structural parameters (lower porosity and smaller pores), where the control hydrogel (without lignin) showed higher surface area, pore volume, and pore size. As a result, the swelling capacity of lignin-based hydrogel decreased, while thermal stability improved, with major degradation occurring at ∽420°C (while ∽415°C for the control). Hence, lignin addition led to a more compact structure with reduced swelling but enhanced rigidity and thermal resistance [38], as shown in Table 1.

A physical mixture involves dispersing or blending lignin with different polymers, where lignin functions as a natural biomass embedded within the polymer matrix. The insertion of lignin into the hydrogel structure through interpenetration or semi-interpenetration is known as the interpenetrating network structure approach. The primary mechanism is the polymerization of free radicals. In the presence of initiators, the phenolic hydroxyl groups in lignin generate free radicals that react with monomer and/or polymer chains to create graft structures [26]. For example, Xia and coauthors [48] prepared thermo-sensitive semi-IPN hydrogels using poly(N-isopropylacrylamide) (PNIPAAm) and lignocellulose with lignin. FTIR confirmed the presence of both amide (PNIPAAm) and hydroxyl (lignocellulose/lignin) groups, indicating successful incorporation and interaction, while scanning electron microscopy (SEM) showed a porous network structure affected by lignin content [48].

IPN systems are advantageous for improving mechanical strength, stability, and multifunctionality because two independent polymer networks are formed without covalent bonding between them. This was demonstrated in hydrogels prepared by Oveissi et al. [49], by incorporating lignin into polyurethane hydrogel as a physically crosslinking component. The abundant polar sites present on the backbone of lignin form a secondary network within the polymer matrix through hydrogen bonding and ionic interactions, thus resulting in a semi-interpenetrating structure. This dual network system improves Young’s modulus, tensile strength, toughness, and elongation at break [49].

They are moderately scalable but usually require multi-step synthesis and sometimes organic solvents. Control over the exact network architecture is limited compared to controlled polymerization techniques. IPNs are widely used in biomedical and drug delivery applications due to their tunable swelling and biocompatibility, but the synthesis complexity can limit precise structural design [50].

Crosslinked copolymerization, in which carboxymethylated lignocellulosic materials are grafted with hydrophilic monomers like acrylic acid, is a typical method for creating lignin-based hydrogels. As a natural cross-linker, lignin strengthens the hydrogel’s structural integrity by creating covalent bonds with polysaccharides. To stabilize the network, artificial cross-linkers such as MBAAm may also be employed. Water retention and swelling capacity of the hydrogel are greatly influenced by the lignin concentration and crosslinking density; optimal absorbency is achieved with moderate crosslinking. Superabsorbent hydrogels that are environmentally benign and biodegradable can be developed using this technique [51, 52].

Munguía-Quintero and coworkers [53] developed a lignin-graft-(poly(acrylamide-co-N,N’-methylenebisacrylamide)) hydrogel/copolymer via free radical crosslinking copolymerization. FTIR confirmed successful grafting. SEM analysis showed that raw lignin had an irregular, fragmented surface, whereas the modified lignin exhibited a more uniform and larger morphology, confirming structural modification. The incorporation of lignin provided active functional groups and a stable backbone, which enhanced thermal stability and adsorption performance (high Pb²⁺ removal). Hence, lignin influenced the hydrogel by improving mechanical stability, functional group availability, and performance, while also contributing to a more robust and crosslinked network structure [53].

This is one of the simplest and most scalable methods, where monomers and crosslinkers polymerize simultaneously to form a hydrogel network. It is widely used in industrial hydrogel production because it requires straightforward reaction setups. However, it often uses radical initiators and chemical crosslinkers that may introduce toxicity concerns, limiting its suitability for sensitive biomedical applications. The control over network structure is moderate compare with controlled radical polymerization techniques [54].

Grafting on the backbone of lignin with unsaturation monomers or other functional compounds increased its reactivity. Grafted lignin can copolymerize with hydrophilic monomers in the presence of a crosslinker to produce a variety of hydrogels for use in a range of applications. Further copolymerization may be possible in most cases when a double bond is introduced into the lignin structure using an unsaturated monomer [55].

Grafted crosslinking involves attaching side polymer chains onto a backbone polymer and then forming a crosslinked network [50]. For example, Rajan et al. [56], prepared lignin-based methacrylate copolymer hydrogels using modified organosolv lignin and hydroxyethyl methacrylate (HEMA). The interaction between lignin and polymer occurs through covalent grafting (HEMA onto lignin) along with additional hydrogen bonding and hydrophobic interaction, which together form a more rigid and stable network. Infrared spectroscopy (FTIR) confirmed covalent bonding and successful copolymerization between lignin and HEMA. Glass transition temperature and increased stiffness indicate formation of a crosslinked, uniform polymer network rather than a physical mixture [56].

This method often uses relatively mild reaction conditions and can incorporate natural polymers, making it attractive for biomedical and environmental applications. However, controlling grafting density and uniformity is difficult, which can lead to heterogeneous network structures. Scalability is moderate, and reproducibility can sometimes be an issue [50].

RAFT (reversible addition-fragmentation chain transfer polymerization) and ATRP (atom transfer radical polymerization) were two popular techniques for creating polymers with controlled and engineered architectures. To create lignin-based hydrogels with well-aligned structures, ATRP and RAFT have both been employed. With respect to ATRP and RAFT polymerizations, “graft-from” and “graft-onto” were two fundamental methods for creating hydrogels. Creating polymers from active areas found on the backbone polymer was known as the “graft-from strategy.” Lignin often functioned as the backbone polymer, allowing the grafted polymers to form from the protein’s active sites. To integrate synthetic polymers with lignin using the “graft-onto” approach, covalent connections are formed between the lignin backbone and the graft polymers’ terminal groups [57–59]. Click chemistry is the most widely utilized reaction to graft guest polymers onto lignin because of its great efficiency and ease of usage [58, 59].

ATRP offers excellent control over molecular weight, polymer architecture, and functional group placement, allowing precise design of hydrogel networks. This makes it highly suitable for advanced functional materials and responsive biomedical systems. However, ATRP typically requires transition metal catalysts (such as copper as residual Cu must be reduced to ppm levels (< 10–50 ppm for biomedical use) due to cytotoxicity) and strict reaction conditions, which may raise toxicity concerns and complicate purification, especially for biomedical uses. Scalability can also be limited due to catalyst removal requirements [58]. This has been depicted by Liu et al. [60], they prepared lignin-based gene delivery copolymers by converting lignin into macroinitiator through esterification of lignin’s hydroxyl groups using 2-bromoisobutyryl bromide and then grafting PDMAEMA chains via ATRP. The resulting copolymers formed DNA-loaded nanoparticles and showed efficient gene delivery. NMR and FTIR confirmed successful synthesis, results showed that shorter PDMAEMA chains gave lower toxicity and better transfection, demonstrating controlled structure-performance behaviour [60].

RAFT polymerization provides high control over polymer structure similar to ATRP, but it does not require metal catalysts. This reduces toxicity issues and makes RAFT more suitable for biomedical and sensing applications. It also allows versatile monomer selection and precise functionalization. However, RAFT requires specific chain transfer agents and may involve longer reaction times, which can affect cost and industrial scalability [58]. For instance, Xu and coresearcher [61] developed a lignin-based methyl methacrylate (MMA)-co-butyl acrylate (BA) hybrid acrylic resin by first synthesizing lignin-graft-polyacrylamide (lignin-g-PAM) as macromolecular chain transfer using RAFT polymerization, and then using it in RAFT mini-emulsion polymerization to copolymerize MMA and BA. NMR and FTIR confirmed the successful formation of the graft copolymer. The results further showed high monomer conversion (~86–90%), stable latex particles, and increased glass transition temperature (~58.6°C) compared to pure resin (−1.3°C), confirming successful incorporation of lignin [61].

There is no single universally best method; the choice depends on the application. Crosslinking copolymerization is best for large-scale and simple hydrogel synthesis, ATRP and RAFT are best for precise structural control, while RAFT is generally considered the most suitable for biomedical applications due to better control and lower toxicity compared to ATRP. IPN systems are preferred when enhanced mechanical strength and multifunctionality are required (Table 2).

A biosensor is an electronic device capable of detecting, transmitting, and recording changes in physiological data [62]. It uses a biological component to detect specific substances and a transducer to convert the detection into an electrical signal. Biosensors offer an inexpensive, extremely sensitive, selective, real-time, and compact method for assessing biomarker changes compared to existing benchtop analytic techniques [63].

A biosensor operates on two main principles: biological recognition and signal sensing. It consists of three key components: A bioreceptor (such as an enzyme, antibody, or DNA) that specifically interacts with the target analyte, a transducer that converts this interaction into a measurable signal (usually electrical or optical), and a signal processing system that amplifies and displays the results. When the analyte binds to or reacts with the biological element, it produces changes such as electron transfer, heat, or ion release, which are then detected by the transducer. Biosensors are designed to provide rapid, accurate, and real-time detection, making them highly useful in healthcare, environmental monitoring, and food safety [64, 65].

As lignin and its derivatives are biocompatible and biodegradable, lignin-based conductive hydrogels are used as biomaterials for bioelectronic sensors that monitor blood pressure, heartbeat, pulse, and human mobility [26]. As lignin is inexpensive and works well with various polymeric materials, it has been used to create biosensor electrodes. Enzymes and non-catalytic peptides that resemble biomolecules have been incorporated into lignin-based biosensors [8]. Lignin-based biosensors, often combined with enzymes, can detect biomolecules such as glucose by producing measurable changes, such as pH or electrical conductivity. Table 3 presents various biosensor applications of lignin-based hydrogels. Lignin-based biosensors operate via well-defined signal transduction mechanisms, where the interaction between a target analyte and a bioreceptor (enzyme, antibody, or peptide) is converted into a measurable signal [26]. Electrochemical biosensors combine biological recognition (such as glucose oxidation) to generate electrons that alter the current, voltage, or impedance [8].

Evaluating the performance of a biosensor is crucial to ensure its reliability and practical applicability. Biosensor performance is typically assessed using key metrics such as sensitivity (ability to detect small changes in analyte concentration), detection range (span over which the response is reliable and linear), signal intensity and signal-to-noise ratio, selectivity (specific response to target molecules), and throughput (efficiency in screening large sample sizes). As illustrated in a study by Ho and coworkers on the optimized lignin-based biosensor with increased signal intensity ~1.5-fold, a wider limit detection ranges up to 640 µM, and higher sensitivity detection, confirming enhanced overall efficiency and reliability [65].

Wang and coworkers [66] created a multipurpose organo-hydrogel sensor using water/glycerol as the dispersion medium, poly (3,4-ethylenedioxythiophene): sulfonated lignin (PEDOT:SL) as conductive fillers, and PAA as the skeleton. The organo-hydrogel sensor sensed neck vibrations, a faint pulse, and limb movement. It also exhibited conductive, self-wrinkling, soft, elastic, and anti-freezing qualities. Physiological signals needed for electromyography (EMG) and electrocardiography (ECG) detection could be transmitted via this conductive hydrogel, as described in Figure 4. The organo-hydrogel is non-toxic and may shield skin from frostbite, according to animal studies and cell culture tests [66].

As a catalyst for hydrogel-based bio-electronic sensors, industrial lignin is also employed. For instance, SL, ferric ions (Fe³⁺), and PAA were the building blocks of a multifunctional hydrogel that was quickly created by Wang and team [68] at room temperature employing a dynamic redox and coordination mechanism (Figure 5). The SL–Fe³⁺ complex speeds up polymerization and permits gelation in a matter of minutes by starting ammonium persulfate (APS) to generate semiquinone and hydroxyl radicals. Excellent mechanical and functional qualities are also imparted by the physically crosslinked network formed by the reversible coordination between Fe³⁺ and SL. The resultant hydrogel has exceptional UV-blocking ability (99.7% at 2 mm thickness), great stretchability (up to 1,680%), conductivity (7.0 × 10^–2 S/m), robust adhesion (up to 36.4 kPa), and high transparency (81%). It also has exceptional self-healing capabilities, recovering up to 85.7% of its stretch and 98.5% of its conductivity after damage. This hydrogel is a very promising platform material for the creation of wearable, flexible, and self-healing biosensors as well as electrical interfaces in human–machine systems, even though it is not a biosensor in and of itself [68].

Flexible strain sensors based on hydrogels can be firmly affixed to the human body and convert mechanical signals (bending, stretching) into electrical ones (resistance, conductivity) due to their unique advantages of flexibility, biocompatibility, and lightweight. This allows for the capture of both large-scale (e.g., joint bending, body movement) and tiny-scale (e.g., pulse, heartbeat, breathing, throat vibration) human body action. Such transduction approaches often involve capacitance, piezo-resistivity, and piezo-electricity [62]. Table 4 shows lignin-based hydrogels in strain sensor applications.

An exceptionally flexible and conductive hydrogel was developed by Zhao et al. [75] for advanced strain sensing through the incorporation of sulfonated lignin-coated silica nanoparticles (LSNs), polyacrylamide (PAM), and ferric ions (Fe³⁺) (Figure 6). Ultrafast gelation within 60 seconds was achieved via the dynamic redox interaction between the catechol groups on the LSNs and Fe³⁺, resulting in the formation of a robust three-dimensional network. The optimized hydrogel (containing 1.5 wt% LSNs) exhibited outstanding mechanical properties, including an elongation of approximately 1,100%, a tensile strength of ~180 kPa, a compressive strength of ~480 kPa, and a low hysteresis ratio (< 15%), ensuring precise strain recovery. In addition, the abundant catechol groups provided effective UV protection (~95.1%) and excellent self-adhesion to a variety of surfaces, including human skin. The hydrogel demonstrated remarkable repeatability and high-fidelity response as a strain sensor over a broad strain range (10–200%), making it highly promising for long-term, skin-conformal wearable electronics for human motion tracking [75].

Pressure sensors are force-sensitive devices that undergo structural changes when physical pressure is applied. These sensors operate by converting, detecting, and quantifying pressure into electrical signals, enabling their use in various electronic applications [82]. The three primary types of pressure sensors are piezoelectric (generate an electrical signal when mechanical stress is applied), capacitive (detect changes in capacitance due to deformation or pressure), and piezoresistive (change electrical resistance in response to applied mechanical strain) sensors. For wearable healthcare monitoring, next-generation piezoresistive sensors should combine high sensitivity with excellent flexibility, compressibility, stretchability, and bending capability, features that are often lacking in traditional piezoresistive sensors made from brittle metals or fabricated on rigid substrates [83]. Pressure sensors, as a subset of tactile sensors, have gained significant attention due to their potential in applications such as precision surgery and diagnostic health monitoring. Hydrogel-based pressure sensors with mechanosensory capabilities can be fabricated from natural polymers rich in functional groups, allowing them to transform pressure input into electrical conductivity output, similar to the mechanism of strain sensors [62]. Table 5 summarizes the various roles of lignin-based hydrogels in pressure sensor applications.

Lignin-based hydrogel sensors generally exhibit good signal stability owing to their crosslinked polymer networks formed through hydrogen bonding, ionic interactions, or metal coordination bonds. These networks help maintain structural integrity during repeated mechanical deformations, such as bending, stretching, or compression, enabling reliable detection of human motion over long periods. However, long-term use may still lead to signal drift because of gradual structural relaxation, hydrogel dehydration, or conductive pathway degradation. Repeated mechanical cycling and environmental exposure can weaken the network, potentially reducing the sensing sensitivity and long-term stability [87].

For wearable and biomedical sensing applications, hydrogels must remain stable under physiological conditions, such as body temperature, sweat exposure, and varying pH. However, continuous exposure to biological fluids, enzymes, and physiological electrolytes can alter the hydrogel network structure, thereby affecting its mechanical strength and conductivity. Over time, swelling, hydrolysis, or partial degradation may occur, which can influence the durability and reliability of the sensing signals [88].

In addition, interference from moisture, salts, and competing ions present in biological fluids can influence the sensing performance. Lignin-based hydrogel sensors often operate through ionic conductivity or resistance changes within hydrated polymer networks. Their performance can be affected by environmental moisture and ions present in sweat or the surrounding media. Water uptake can change the swelling degree of the hydrogel and modify the conductive pathways, leading to variations in the electrical signal. Similarly, ions such as Na⁺, K⁺, or Cl^– can influence ion transport within the hydrogel matrix, causing fluctuations in resistance to moisture, and ionic interference remains an important challenge for practical sensor deployment. This highlights the need for improved structural design and protective strategies for stable sensing performance [89].

Moisture may change the electrical conductivity or swelling behavior of lignin-based composites, whereas ions such as metal cations or electrolytes can interact with the functional groups of lignin (e.g., phenolic or carboxylic groups), potentially altering the sensing signal. These interactions may lead to signal drift, reduced selectivity, and decreased reproducibility in complex biological environments [90].

Drug delivery systems aim to enhance the therapeutic efficacy and disease-targeting properties of a drug molecule at a controlled rate, along with reducing severe adverse effects [50]. Currently, lignin-based drug transporter systems, such as hydrogels, have been employed for efficient drug delivery. Active pharmaceutical ingredients (API) can be incorporated into lignin-based carriers via inclusion, adhesion, encapsulation, and chemical modification. Lignin can (i) safeguard light-sensitive compounds, (ii) facilitate the dispersion of the active components in either liquid or solid composites, (iii) prevent the unintentional loss of volatile and potentially harmful active ingredients, and (iv) substitute synthetic polymers currently employed in these applications [9].

The unique properties of hydrogels, such as their ability to retain water, biocompatibility, and controllable swelling behavior, have made them increasingly valuable in drug delivery systems. The gel matrix can be easily manipulated by adjusting the type and quantity of crosslinking agents because they are porous. In addition, drugs can be loaded into the gel matrix more easily. The drug is released in a rate-dependent manner based on the diffusion coefficient of the drug molecules through the gel network [91]. For example, Preet and coworkers prepared lignin–chitosan–chondroitin sulphate–PVA hydrogel. The results showed controlled and pH-dependent drug release (higher at pH 7.4), indicating a diffusion-based release owing to the porous lignin network [92]. Similarly, Morales and coinvestigators [93] prepared lignin-based hydrogels using PVA and different types of modified lignin (alkaline and organosolv lignin from almond and walnut shells). The hydrogel followed the Korsmeyer-Peppas model and exhibited Fickian diffusion behavior (n < 0.5), indicating that the drug diffused out mainly through the hydrogel matrix [93].

Hydrogels can be administered via various routes, including systemic distribution by intravenous infusion, local needle injection, topical administration, and surgical implantation. The choice of delivery route is based on the dose size and patient compliance [91]. Lignin-based hydrogels can deliver both water-soluble and lipid-soluble drugs because of the presence of hydrophobic and hydrophilic groups in the lignin backbone, making them suitable for drug delivery applications [8].

Lignin possesses a highly aromatic structure composed of phenylpropane units, which enables strong π–π stacking interactions with drug molecules that contain aromatic rings [94]. These interactions occur when the delocalized π-electron systems of the aromatic rings of lignin align with the π-electron clouds of aromatic drug molecules, creating stable non-covalent associations. Such stacking interactions help enhance the drug loading capacity and stabilize the drug within lignin-based carriers, including lignin-derived metal–organic frameworks (MOFs) and covalent organic frameworks (COFs) [95]. For instance, Zhou and coworkers [96] developed lignin hollow nanoparticles (LHNPs) from renewable lignin using a self-assembly method as a carrier for doxorubicin (DOX) (an anticancer drug). They found that LHNPs exhibited a good drug loading capacity (~60%). The drug loading mechanism involves H-bonding, electrostatic attraction, and π–π interactions between lignin and DOX [96].

Drug release from lignin-based systems generally follows diffusion- or swelling-controlled mechanisms. Commonly applied release kinetics models include the zero-order (constant release rate), first-order (concentration-dependent release), Higuchi (diffusion-controlled release proportional to the square root of time), and Korsmeyer-Peppas models, which help determine whether the release mechanism is Fickian diffusion, anomalous transport, or polymer relaxation-controlled. In many lignin-based hydrogels and nanoparticles, the release behavior fits the Higuchi or Korsmeyer-Peppas models, indicating that drug diffusion through the porous polymer matrix is the dominant mechanism [97].

In lignin-based materials, π–π stacking not only facilitates the efficient encapsulation of hydrophobic or aromatic drugs but also contributes to controlled and sustained drug release, as the drug molecules remain temporarily bound to the lignin matrix. Environmental factors, such as pH, solvent polarity, and ionic strength, can influence these interactions, enabling responsive drug release under physiological conditions [98]. Farhat et al. [99] developed pH-responsive hydrogels using natural polymers, such as lignin, starch, and hemicellulose. Drug release was controlled by swelling-dependent diffusion, where higher swelling (at higher pH) led to a faster release of molecules. The release mechanism follows anomalous transport (0.5 < n < 1), indicating that both diffusion and polymer relaxation control drug release. Lignin influences drug release by contributing to the crosslinked structure, where increased crosslinking reduces swelling and slows down the release. Its natural structure helps to form stable, controlled-release hydrogels [99].

Importantly, lignin-based carriers are often stimulus-responsive in physiological environments. Under different pH conditions (such as acidic tumor microenvironments or gastric fluid), ionizable groups in lignin (e.g., phenolic and carboxyl groups) undergo protonation or deprotonation. At low pH, protonation can weaken electrostatic interactions and hydrogen bonding, thereby accelerating drug release. At neural or basic pH, deprotonation may increase swelling and electrostatic repulsion within the hydrogel network, thereby enhancing drug release. Additionally, lignin is susceptible to enzymatic degradation, particularly by oxidative enzymes (e.g., peroxidases and laccases), which can gradually break down the polymer matrix and promote controlled drug release. This enzyme responsiveness supports biodegradability and reduces long-term accumulation in the body [6, 19].

Zhu and coworkers [25] developed a pH-responsive sprayable hydrogel using carboxymethyl chitosan combined with trans-resveratrol-loaded lignin-based nanoparticles as the drug carrier. The drug release mechanism depended on pH, it followed Fickian/non-Fickian diffusion at neutral and alkaline pH and showed zero-order release at skin-like pH (∽6.0). Lignin-based nanoparticles controlled the release via pH-sensitive solubility and thus enabled tunable drug release behaviour [25]. Recent developments in lignin-based hydrogels for drug delivery are summarized in Table 6.

Wound healing is a normal physiological mechanism associated with tissue structural injury, usually divided into four stages: homeostasis, inflammation, proliferation, and remodelling, involving various cells and endogenous substances [50].

To speed up and to provide complete wound healing, several types of wound dressing have been identified such as gauze, hydro fibres, film, foam, hydrocolloids and hydrogels. Although, several currently utilized wounds dressings exhibit limitations, for example, they may obstruct the circulation of gases between the wound and its surroundings, thereby making it challenging for both nutrients and oxygen to pass through the wounded area. Furthermore, some dressings are difficult to remove, may not offer appropriate protection against microbiological invasions or preserve sterility, and can provoke allergic reactions [107].

Hydrogels offer several advantages, such as they have the ability to absorb and hold a considerable amount of water in the network, allowing it to keep a humid environment in the wound region, thereby improving wound therapy and management [108]. Moreover, hydrogels offer a flexible framework for incorporating other substances, including medications, antimicrobial and antibacterial agents, as well as additional biomolecules, which increases their overall effectiveness in accelerating wound healing [109]. Microbes can contaminate wounds and adhere to dressings, increasing infection risk, as most wound infections are caused by bacteria. Lignin, a natural biopolymer, is an excellent agent for wound dressing as it possesses various functional groups in its structure, which are responsible for the antimicrobial, antioxidant, and anti-inflammatory activity as described in Figure 7.

The antioxidant activity of lignin is primarily attributed to its abundant phenolic and oxygen-containing functional groups, which are capable of neutralizing reactive free radicals. Phenolic hydroxyl groups present in lignin can denote hydrogen atoms or electrons to reactive radicals through single-electron transfer and hydrogen atom transfer mechanism, thereby terminating oxidative chain reactions. This radical scavenging ability enables lignin to reduce the accumulation of reactive oxygen species (ROS) that are responsible of oxidative stress in biological systems [110]. From a clinical perspective, controlling oxidative stress is particularly important in wound healing and tissue regeneration, where excessive ROS can damage cellular membranes, proteins, and DNA, ultimately delaying tissue repair. By scavenging free radicals, lignin-based materials can help protect surrounding tissues, reduce inflammation, and promote a favorable environment for cell proliferation and healing [111]. As showed by the lignin–chitosan–chondroitin sulphate–PVA hydrogel made by Preet et al. [92], which showed antioxidant activity by effectively neutralize free radicals and reduce oxidative stress. This activity is mainly due to lignin’s phenolic hydroxyl groups, which donate hydrogen atoms or electrons to stabilize free radicals, thereby preventing cellular damage [92].

In addition to antioxidant effect, certain functional groups in lignin, such as methoxy and epoxy groups, contribute to antibacterial activity by disrupting bacterial cell membranes and inducing cell death [111]. For instance, Ciolacu and team [112] developed cellulose-modified lignin (CLE) hydrogels using cellulose and chemically modified lignin, cross-linked with epichlorohydrin. Antibacterial activity was tested against Escherichia coli and Staphylococcus aureus, showing increased effectiveness with higher lignin content. Lignin inhibits bacteria by its hydroxyl and methoxyl groups interacting the cell membrane of bacteria, causing membrane disrupting and leakage of cellular contents, making them suitable for wound healing application [112].

Lignin naturally acts as a defence barrier and can inhibit bacteria, fungi, and viruses, making it a promising natural antimicrobial material. The antibacterial activity of lignin is mainly associated with its phenolic hydroxyl groups, which can damage bacterial cell membranes and lead to cell lysis. Lignin has been reported to inhibit certain fungal species, although the exact mechanism of fungal suppression is not yet clearly understood [113].

The anti-microbial effectiveness largely depends on the source of lignin and the extraction method used, as these factors influence its chemical structure and functional groups. For instance, Kraft lignin has been reported to effectively inhibit gram-positive bacteria such as Listeria monocytogenes and Staphylococcus aureus, while other lignin types extracted from eucalyptus have shown activity against both gram-positive bacteria (Bacillus cereus, Staphylococcus aureus) and gram-negative bacteria (Escherichia coli, Salmonella enteritidis). Research has reported that kraft lignin can inhibit the growth of fungi such as Aspergillus niger, Mucor circinelloides, and Penicillum solitum [113]. However, kraft lignin derived from eucalyptus has demonstrated particularly strong antifungal activity against Aspergillus niger compared to other lignin types [114].

In contrast, lignosulfonates display broad antimicrobial activity, which is mainly attributed to their anionic surfactant nature due to presence of sulfonate groups. These charged structures enable lignosulfonates to interact with cellular components such as lipids and proteins, disrupting normal microbial cell functions and inhibiting growth. Soda lignin has been reported to shown moderate antibacterial activity, particularly against gram-positive bacteria such as Staphylococcus epidermidis and Bacillus species. However, it has shown little or no activity against microorganisms, such as Escherichia coli and Aspergillus niger. The anti-microbial effectiveness of soda lignin can also vary depending on processing conditions such as extraction temperature and biomass source [115]. Thus, lignin-based hydrogels offer numerous advantages in wound healing applications in Table 7.

Because of its outstanding antioxidant activity and remarkable ability to absorb UV radiation, lignin hydrogel has been proposed as a suitable alternative for cosmetic applications [122]. The UV absorption property of lignin is due to the presence of UV chromophore groups such as phenolics, hydroxyl groups (OH), conjugated double bonds, and carbonyl groups (C=O) [123]. However, limited studies have been conducted on the development and use of lignin hydrogels in cosmetic formulations. For example, Darmawan et al. [124] developed a natural sunscreen formulation using tengkawang butter (as the base) combined with different types of lignosulfonates (Ca, Mg, and Na forms) at varying concentrations (1–10% w/w). The SPF evaluation showed a significantly higher UV protection, with sodium lignosulfonate due to lignin’s chromophore structure; additionally, π–π stacking increases light absorption efficiency. However, the study has key limitations such as poor solubility and dispersion of lignin in lipid-based systems, leading to stability issues, time-consuming formulation, and inconsistent SPF behaviour. Moreover, results are limited to in-vitro studies, requiring further in vivo testing and compatibility assessment before practical cosmetic application [124].

Wang and team [125] produced a natural hair conditioner with a micellar lignin hydrogel emulsion system that has 26% lignin and 6% coconut oil as triglycerides. The results showed that the lignin gel emulsion remains stable after one year of storage; this suggests a longer shelf life for possible commercial use. Compared to the commercial product, the lignin gel-based conditioner effectively smooths damaged hair, as shown by a 13% reduction in wet combing force. Additionally, due to its phenolic component, lignin offers natural UV protection and significant antioxidant activity. These findings indicate that developing a completely natural hair conditioner with lignin gel emulsions could help advance sustainable personal care products [125].

Another study demonstrated the use of a lignin hydrogel patch in the treatment of Atopic dermatitis, a chronic skin disease. Trinh and co-workers prepared a therapeutic antioxidant lignin hydrogel patch using lignin powder and the cross-linker poly (ethylene glycol) di-glycidyl ether (PEG-DGE). The study includes the AD mouse model and the results demonstrate that the hydrogel patch successfully reduced the thickness of the epidermis, inhibited inflammation, and reduced oxidative damage to DNA, which helped to regulate oxidative stress in cellular functions. The results of these studies suggest that lignin hydrogels can significantly reduce the inflammatory immunological response associated with atopic dermatitis due to their inherent ROS-scavenging characteristics. Thus, the study shows that the potential application of lignin hydrogel patches in the treatment of various skin diseases associated with inflammation and oxidative stress in the skin [126].

Despite the promising antioxidant, UV-protective, and antimicrobial properties of lignin, its translation into commercial cosmetic formulation remains limited due to several scientific and regulatory challenges. One major limitation is the intrinsic dark brown color of lignin. Most technical lignin, such as kraft and soda lignin, possesses a dark to black coloration. When incorporated into cosmetic formulations such as creams, lotions, or sunscreens, this color can significantly alter the appearance of the final product. Since cosmetic products are highly dependent on visual appeal and consumer perception, the strong pigmentation of lignin may limit its use or require additional purification and modification processes to produce lighter or color-controlled derivatives [127, 128].

Restu and team [129] developed a natural cream-based sunscreen using lignin as the active UV-protection ingredient. The SPF study showed a maximum SPF ≈ 15 at 2% lignin, indicating effective UV-protection. However, a key drawback of the study was its intrinsic dark brown color, which negatively affects the aesthetic acceptability of cosmetic products, along with poor solubility and dispersion issues in cream formulation. As a potential solution, the study implies that reducing particle size, improving purification, or modifying lignin chemically can enhance dispersion and performance. Additionally, formulation strategies (better emulsification system) may help overcome these limitations, although further optimization and research are still required for practical cosmetic use [129].

Another important challenge is the unpleasant odor associated with technical lignin, particularly kraft lignin, which arises from volatile organic compounds such as guaiacol, acetic acid, and sulfur-containing molecules generated during pulping processes. This odor can negatively affect the sensory quality of cosmetic formulations and requires additional purification or chemical modification steps [130].

In addition, lignin exhibits poor solubility, dispersion, and compatibility with conventional cosmetic bases, which can lead to aggregation, phase separation, and instability in emulsions or gels. These formulation difficulties arise mainly from the highly heterogeneous and complex aromatic structure of lignin [131].

Lignin is still considered a novel bio-based cosmetic ingredient, and therefore requires extensive toxicological evaluation, skin irritation testing, and regulatory approval before commercialization. The lack of comprehensive long-term safety data and standardized quality specifications for cosmetic-grade lignin further delays its regulatory acceptance and industrial adoption [127].

Tissue engineering is a multidisciplinary science that aims to repair and rejuvenate diseased and deteriorated tissues and organs using appropriate and biocompatible substances that imitate native and original tissues, resulting in the restoration and enhancement of tissue function [132].

Various techniques can be used to generate tissues or organs. The common strategy associated with the concept of tissue engineering is the utilization of healthy cells seeded on a natural or fabricated extracellular matrix (known as a scaffold) to construct implantable segments of the organism [133], as illustrated in Figure 8. Scaffolds serve the following primary purposes: (a) transport the propagated cells to the intended location within the patient's body; (b) stimulate interactions between the cells and the biomaterial; (c) encourage cell adhesion; and (d) allow for the proper passage of gases and growth factors to assure survival, development, and differentiation of cells [134].

Recently, hydrogels have been most widely used as scaffolds due to their high swelling capacity, ability to mimic the extracellular matrix, and desirable mechanical properties. It has been demonstrated that scaffolds made of lignin are effective in stimulating the production of new bone. This is because lignin has the ability to promote osteogenic cell proliferation, which is a necessary step in the process of bone formation. Furthermore, additional findings indicated that lignin might rectify aberrant bone remodelling by suppressing osteoclast differentiation [135]. For bone regeneration, the scaffold should possess high mechanical strength. Lignin-based hydrogels illustrated excellent mechanical properties. It has been shown that the stiffness, tensile strength, and storage modulus of hydrogels all rise substantially with an increase in the concentration of lignin, thereby making them suitable for bone regeneration applications [136].

Wang and coworkers [137] developed a biomimetic bone scaffold using electrospun lignin/polycaprolactone nanofibers, which were mineralized in simulated body fluid to form bone-like hydroxyapatite (Hap). The phenolic and hydroxyl groups of lignin chelate Ca²⁺ ions and promote nucleation and growth of Hap through co-precipitation with PO₄^3–, mimicking natural bone mineralization. This Hap-coated surface enhances osteogenic cell proliferation, promoting osteoblast adhesion, which strengthens cell-matrix interactions and supports bone-like tissue development. However, limitations include restricted cell penetration due to dense nanofiber structure and the study being limited to in-vitro evaluation, requiring in-vivo validation and scalability assessment for clinical application [137].

Zheng and team [138] developed a bone-protective therapeutic system using lignin-carbohydrate complexes (LCC) isolated from wheat straw. These materials help to protect bones. Lignin part (LCC-A) involves strong anti-oxidant/ROS scavenging activity, and carbohydrate part (LCC-B) acts by promoting osteogenic cell proliferation and differentiation by activating natural cell defence pathways. The limitations are that the exact working mechanism is not fully clear, and it is still in the early research stage [138].

Here, Table 8 demonstrates the potential of lignin-based hydrogel applications in tissue engineering.

Stimuli-responsive hydrogels are hydrogels that react rapidly to slight variations in chemical or physical conditions. They are also referred to as intelligent, smart, or environmentally sensitive hydrogels [140]. These systems can respond to a variety of stimuli, including chemical factors (e.g., pH, ions) and physical factors such as temperature, light, or magnetic fields [141].

For developing lignin-based hydrogels that respond to stimuli, it is useful either to directly synthesize sensitive molecules within the hydrogel matrix or to incorporate such molecules into preformed lignin hydrogels [142]. For example, the most common approach for producing thermo-responsive lignin-based hydrogels is to introduce temperature-sensitive monomers into the lignin hydrogel network [7]. Similarly, pH-responsive polymers, a subset of stimuli-responsive polymers, can alter their structure and functional properties in response to the pH of the surrounding medium. Due to the presence of hydroxyl and carboxyl groups, lignin is naturally susceptible to pH changes. As a result, pH-responsive polymers can be coupled with lignin to create pH-sensitive lignin-based functional materials [143].

Light-responsive (or photo-responsive) hydrogels are another type of stimuli-responsive system and are generally categorized into two types: photodynamic therapy (PDT) and photothermal therapy (PTT). PDT can be applied in antimicrobial photodynamic therapy (APDT) and as antimicrobial coatings for treating wounds, acne, and other microbial infections. Upon exposure to an appropriate wavelength of light, the photosensitive substance becomes excited, and during relaxation, oxygen molecules are converted into ROS, which destroy bacterial cells. PTT, on the other hand, uses photothermal agents (PTAs) to generate heat in order to damage or kill abnormal cells or tissues. Both approaches act through direct structural damage rather than metabolic interference, resulting in minimal bacterial tolerance [144]. A key challenge in antimicrobial light therapy is the aggregation and uncontrolled release of photosensitive or photothermal agents. This limitation can be addressed by incorporating these agents into compatible hydrogels, which enable stable encapsulation and efficient delivery [145].

Additionally, lignin-based hydrogels offer distinct advantages in terms of sustainability, intrinsic antioxidant activity, and UV-blocking capacity in comparison to synthetic smart polymers such as PNIPAM, PEG-based systems, and other engineered stimuli-responsive networks. Lignin-based hydrogels and synthetic polymer hydrogels differ significantly in terms of their origin, structural characteristics, functionality, and performance. Lignin-based hydrogels are derived from lignin (natural source) as compared to synthetic polymer hydrogels produced through polymerization of synthetic monomers such as PEG, PVA, polyacrylamide (PAAm), and poly(N-isopropylacrylamide) (PNIPAM). Due to their natural origin, lignin-based hydrogels are considered more sustainable and environmentally friendly [35, 36].

Unlike many petroleum-based synthetic polymers, lignin shows low toxicity, natural antioxidant activity, UV resistance, and enzymatic degradation, which make it attractive for biomedical and environmental applications. In terms of swelling behaviour, lignin-based hydrogels typically exhibit swelling ratios around 500–900%, and in some lignocellulosic composites even above 1,000%, which is comparable to many synthetic polymer systems. However, synthetic superabsorbent polymers such as poly (acrylic acid)-based systems can reach much higher swelling capacities, up to 2,000%. Mechanically, lignin improves rigidity and increases storage modulus (G’ > G”) due to its aromatic and nano-aggregated structure, but synthetic double-network hydrogels can achieve superior tensile strength (often 1–10MPa) and very high elongation (> 1,000%), making them more flexible and mechanically tunable [146].

However, the major limitation of lignin is its complex, heterogeneous, and source-dependent structure (e.g., kraft, orhanosolv, lignosulfonate), which leads to variability and lower reproducibility compared to precisely engineered synthetic polymers. Moreover, while lignin-based hydrogels show pH and moderate temperature responsiveness due to hydroxyl and carboxyl groups, synthetic smart polymers can be designed with highly controlled stimuli responsiveness, such as exact lower critical solution temperature (e.g., ~32°C in PNIPAM). Therefore, hybrid systems combining lignin with synthetic polymers are often considered the most promising strategy to balance environmental sustainability with high-performance material properties [147]. The various applications of stimuli-responsive lignin-based hydrogels are summarized in Table 9.

Conductive hydrogel-based devices have drawn a lot of interest in the fields of wearable devices, physical activity, and personalized drug therapy. Hydrogel devices require strong conductivity to convert external mechanical inputs into feasible electrical signals. These systems require a consistent electric supply of external energy more significantly, when employed as strain sensors or electronic patches/skin [69]. This external energy may be accomplished via a variety of techniques, including thermal, battery-based, electrochemical, and supercapacitor devices, although supercapacitors receiving popularity due to their widespread uses and higher performance [152]. Supercapacitors, a category of electrochemical energy storage systems, offers a feasible solution for energizing wearable bioelectronics and implantable healthcare devices. Wearable and implantable electronics (WIEs) are primarily made up of circuits, power units, and sensors or conducting electrodes. Since they are often affixed to the human body either internally (implanted) or outwardly, each component must be small, thin, flexible, secure, and comfortable. Numerous WIEs have been created to track physiological responses including blood pressure, heart rate, glucose levels, and neurological activity, allowing for rapid and precise diagnosis and therapy implementation, as well as evaluation of treatment effectiveness [153]. Also, supercapacitors provide a secure and reliable energy source for implantable medical devices, including drug delivery system, pacemakers, and neurological implants [154]. In the supercapacitor, hydrogels can be used as an electrode, electrolyte, or both functions simultaneously [152]. Electrolytes, a key component of capacitors, batteries, and other electronic items, are vital carrier of ions as they move during charging and discharging and have been widely employed in energy storage devices and flexible sensing. In comparison to conventional electrolytes, such as pure solid and liquid electrolytes, hydrogel electrolytes have received a lot of attention due to their high mechanical properties, rigidity, and excellent environmental adaptability [143]. Generally, lignin has been employed exclusively as an electrolyte and electrode material. It is a strongly crosslinked aromatic polymer with a considerable number of carbonyls and phenolic or phenolate groups. Due to these unique physicochemical features, lignin is regarded as a potential candidate for the development of efficient electrodes and electrolytes [26]. Currently, the most common lignin-based electrolytes are hydrogels used to build solid-state supercapacitors. At present, there are limited techniques for turning lignin into electrolytes for supercapacitors, thus more straightforward preparation techniques need to be investigated [155]. Table 10 demonstrates recent advancements related to lignin-based hydrogel electrolytes in the field of energy storage devices.