MXene-cellulose composite for healthcare applications: synthesis, properties and future outlook

Introduction

Modern healthcare systems are under increasing strain due to the escalating prevalence of chronic diseases, demographic aging, emerging infectious threats, rising treatment costs, and inequitable access to care (Zhou et al., 2025; Lyu et al., 2021; Gong et al., 2024; Chen T. et al., 2025; Jin et al., 2017). These persistent issues significantly affect patient outcomes, system efficiency, innovation, and global health. In response, there has been substantial progress in developing healthcare solutions through nanotechnology. Among these, the integration of 2D nanomaterials with biomaterials shows great promise for advanced applications such as biosensing, wound healing, drug delivery, and tissue engineering (Kumar et al., 2023; Xia and Qian, 2025; Huang et al., 2022). This potential stems from their unique combination of properties, particularly biocompatibility and superior electronic performance, a synergy that is difficult to achieve with other conductive materials while maintaining safety (Huang et al., 2021; Huang et al., 2024; Amara et al., 2023).

Recently, a novel class of materials known as MXenes has emerged as a promising candidate for developing advanced composite materials for healthcare applications. First reported in the early 2010s, MXenes are a group of 2D transition metal nitrides, carbides, and carbonitrides that exhibits excellent thermal conductivity, hydrophilicity, stability, and versatile surface functionality due to their rich–OH, –F, and–O groups (Anasori et al., 2015; Gogotsi and Anasori, 2019; Naguib and Gogotsi, 2015). In addition, MXenes possess high electrical conductivity (>20,000 S cm^-1) and outstanding electrochemical performance (capacitance >2800 F cm^-3), making them suitable for applications such as health monitoring, wearable strain sensors, and more. However, their practical implementation is constrained by nanosheet restacking, agglomeration, and limited structural stability when processed alone, which can diminish accessible surface area and electrochemical performance.

To address these limitations, composite engineering strategies have been extensively explored. Among various host matrices, cellulose has emerged as a particularly promising candidate due to its renewability, biodegradability, low toxicity, and intrinsic hydrophilicity, which promotes homogeneous (Shaheen et al., 2024). The formation of MXene–cellulose composites enable the development of interconnected conductive networks within a mechanically robust and biocompatible scaffold. Such architectures facilitate efficient electron and ion transport, enhance mechanical integrity, and improve signal responsiveness in biomedical systems (Yang et al., 2022; Shayan et al., 2025). Moreover, the high aspect ratio and thermal stability of MXene nanosheets contribute to localized heat dissipation and structural durability, attributes that are critical for wearable and implant-adjacent applications (Abhinav et al., 2025; Khan et al., 2025; Lim et al., 2024; Sun et al., 2025).

Beyond functional performance, the integration of MXenes with bio-derived polymers addresses growing sustainability concerns in advanced materials development. Incorporating MXenes into cellulose and other bio-based matrices enhances environmental compatibility, reduces toxicity risks, and supports long-term biomedical safety (Al-Fakih et al., 2024; Luo et al., 2025; Li et al., 2025). These characteristics position MXene-cellulose composites as promising candidates for wound dressings, flexible biosensors, and human motion monitoring systems, where mechanical flexibility, conductivity, and biocompatibility must coexist within a single material platform (Kang et al., 2024; Mohammadi Shahandashti et al., 2025). Throughout this manuscript, composites comprising cellulose and MXene will be referred to as MXene-cellulose composites, unless otherwise specified.

Despite rapid progress, several fundamental challenges remain. Existing studies have predominantly focused on the intrinsic physical and electrochemical properties of MXene nanosheets, while the interfacial chemistry governing their interaction with biopolymer matrices remains insufficiently understood (Gusain et al., 2024). Furthermore, conventional MXene synthesis often relies on harsh etching chemistries, raising concerns regarding environmental impact, scalability, and suitability for biomedical translation (Khalid et al., 2024; Shaji et al., 2025). Achieving uniform dispersion, strong interfacial bonding, and balanced mechanical-electrical performance within biodegradable matrices continues to present significant materials engineering challenges (Khalid et al., 2024; Shaji et al., 2025).

This review aims to bridge existing knowledge gaps by examining the synergistic benefits of integrating MXenes with cellulose to advance their application in healthcare technologies, with particular emphasis on wound dressing and human movement monitoring. It provides an overview of MXene/cellulose composite preparation methods, discussing their respective advantages and limitations in these contexts. Finally, the review concludes with an analysis of current challenges and a future outlook for MXene–cellulose composites in wound care and movement monitoring applications.

MXenes

In recent years, three-dimensional ternary or quaternary compounds, referred to as MAX phases, have been frequently chemically exfoliated to produce a family of transition metal carbides, nitrides, or carbonitrides, better known as MXenes (Dutta et al., 2025; Kitchamsetti et al., 2025; Saxena et al., 2025). The MAX phase possesses a chemical formula expressed by Mn+1AXn (n = 1, 2, 3), in which M stands for early transition metal elements, including Sc, Ti, Zr, V, Nb, Cr, and Mo, while most of the A is made up of group III and IV elements, such as Al, Ga, and In, X refers to C and/or N elements. These materials are important because they are the crucial precursors for creating two-dimensional (2D) MXene materials by selectively etching away the ‘A’ layers (Amani et al., 2024; Anasori et al., 2017). The general formula for MXenes is M_n+1X_nT_x (n = 1–3), where M represents a transition metal (such as Sc, Ti, Zr, Nb, and so on), while X refers to C and/or N elements and the T_x represents -OH, -O, or -F terminations coming out of the synthesis processes (Naguib and Gogotsi, 2015; Anasori et al., 2017; Naguib et al., 2011). Figure 1 presents the schematic diagram of MAX phase and MXene structures (Naguib et al., 2014).

Besides, MXenes may also be fabricated through the so-called layered compounds, such as Zr₃Al₃C₅ and Mo₂Ga₂C (Meshkian et al., 2015; Halim et al., 2016; Zhou et al., 2016). Since the discovery of the 2D complex Ti₃C₂T_x in 2011, approximately thirty molecules of MXenes were synthesized and a number more were theoretically forecasted (Naguib et al., 2011).

Large surface area, high electrical conductivity, and tunable surface chemistry make MXenes promising materials for energy storage, catalysis, sensing, and electronics. Because of their unique properties and range of applications, MXenes are well placed to meet the challenges created by advanced technological developments (Shuck et al., 2020).

Synthesis of MXene

Since the discovery of graphene in 2004, research on two-dimensional (2D) materials has expanded significantly (Gogotsi and Anasori, 2019). By 2011, this momentum led to the discovery of MXenes, which can be synthesized through both top-down and bottom-up approaches (Naguib et al., 2011; Naguib et al., 2021). In top-down synthesis, layered crystalline materials are exfoliated into MXene nanosheets (Gogotsi and Anasori, 2019). The most widely used exfoliation technique relies on direct hydrofluoric acid (HF) etching, where bulk MAX phase precursors are immersed in HF to selectively remove the A-layer (Jiang et al., 2022; Shayesteh Zeraati et al., 2021). For example, in Ti₃C₂T_x MXene production, HF is used to etch out aluminium (Al) (Shayesteh Zeraati et al., 2021; Wu et al., 2017). This process typically requires around 24 h at room temperature, using HF concentrations between 30% and 50% (Wu et al., 2017; Kumar et al., 2022). Ahmed et al. (2017) synthesized Ti₃C₂ MXene via HF etching. The MAX phase was first milled for 24 h and then sintered at 1,350 °C for 2.5 h under an inert atmosphere. The resulting particles were added to 48% HF and stirred at room temperature for 18 h, followed by repeated washing with deionized water until the pH reached 6. The obtained Ti₃C₂T_x was subsequently exfoliated through sonication to produce few-layer and multilayer stacks. After HF etching, the c-lattice parameter increased from 18.6 Å to 20.0 Å, and the d-spacing expanded from 0.929 nm to 0.997 nm. The authors noted a considerable loss of crystallinity and evident structural distortion. Beyond concerns about the quality of MXene produced through HF etching, the use of concentrated HF also poses significant challenges due to its high toxicity, strong corrosiveness, and the complex waste management requirements associated with it (Khazaei et al., 2015). Additionally, production costs tend to be higher than those of conventional materials (Shingange and Mokhena, 2026). Beyond these concerns, MXenes containing–F functional groups can pose risks for certain biomedical applications. Therefore, surface modification or integration with other biocompatible materials is often necessary to improve their safety and make them suitable for biomedical use, especially for wound dressing (Vasyukova et al., 2022; Kumar and Vankayala, 2025). For instance, modifying Ti₂C-MXene, originally produced through HF etching, with collagen has been shown to reduce its in vitro toxicity and reduced the oxidative stress. Kumar and Vankayala (2025) reported a user-friendly and precise strategy for transforming HF-produced MXenes into materials with enhanced oxidation stability, uniform particle size, and consistent colloidal behaviour, features that are essential for biomedical applications. Building on conventional organic-solvent-assisted intercalation and collection (OAIC) techniques, the authors developed an improved method capable of producing MXenes with highly reproducible properties. In their approach, Ti₃C₂ MXene was first synthesized through traditional HF etching, followed by Dimethyl sulfoxide (DMSO)-assisted intercalation to achieve delamination. The material was then washed using dichloromethane (DCM) and subjected to six cycles of sonication and centrifugation in a 1:1 DMSO:DCM mixture. The resulting pellet was washed with a water/ethanol mixture to obtain Ti₃C₂ MXene sheets. These sheets were further sonicated in the presence of L-ascorbic acid and allowed to settle for 24 h before vacuum filtration. This procedure yielded MXene flakes with excellent oxidative stability, a uniform particle size of approximately 217 nm, and a high yield of ≥75%, as illustrated in Figure 2. Such surface and structural modifications produce MXenes with properties suitable for use in medical diagnostics and therapeutic applications. These studies indicate that MXenes with carefully tailored surface functionalities can be designed to suit the intended application (Rozmysłowska-Wojciechowska et al., 2020).

Other studies addressed some of these challenges associated with HF etching through indirect HF etching processes (Naguib et al., 2021; Zhang et al., 2020; Wei et al., 2021; Yao et al., 2021; Zheng et al., 2018). This method generates HF on site, commonly through mixtures such as hydrochloric acid (HCl)/Lithium Flouride (LiF), reducing direct handling of concentrated HF. The advantages of this method include enhanced interlayer gap with minimum crystal defects as well as reasonable yield (Shayesteh Zeraati et al., 2021; Zhang et al., 2020). The enhanced interlayer spacing results from the presence of Li⁺ ions, particularly when LiF is used in excess (Yao et al., 2021; Zheng et al., 2018; Lipatov et al., 2016; Ghidiu et al., 2014). These Li⁺ ions intercalate between the MXene sheets, preventing their restacking after the etching process. This method removes the need for an additional exfoliation step involving organic molecules, which is typically required in HF-based synthesis routes. For instance, Lipatov et al. (2016) employed a LiF:MAX ratio of 7.5:1 without including a sonication step. This approach produced larger, high-quality MXene flakes, attributed to the intercalation of Li⁺ ions between the layers, which facilitated effective Al removal and eliminated the need for mechanical exfoliation. Nonetheless, the resulting MXenes often contain–F surface terminations, which decrease their stability and limit their suitability for biomedical applications. Other on site HF-generating etching methods employ fluoride salts, such as Potassium hydrogen difluoride (KHF₂) (Feng et al., 2017), Sodium hydrogen difluoride (NaHF₂) (Feng et al., 2017), and NH₄HF₂ (Feng et al., 2017; Halim et al., 2014), etc. These salts offer a milder and more cost-effective alternative to direct HF etching. Similar to the HCl/Lif approach, this method enables simultaneous etching and ion intercalation, resulting in high-quality MXenes. Halim et al. (2014) compared MXene synthesis using HF and Ammonium hydrogen difluoride (NH₄HF₂) as etchants. They found that NH₄HF₂ enabled simultaneous etching and intercalation. Due to the incorporation of NH₃ and NH₄ ⁺ species, the resulting MXene exhibited an expanded lattice parameter of ∼25 Å, i.e., about 25% larger than that of HF-etched samples. A major limitation of in situ HF-generating etching methods is the extended processing time, which can vary from 2 h to few days. For example, Feng et al. (2017) reported that at least 8 h at 60 °C is sufficient for effective Al removal when using NaHF₂. Similar trends were observed with KHF₂, where 24 h of reaction yielded substantial amounts of MXene. In contrast, NH₄HF₂ proved more efficient; at 60 °C, only 2 h were required to completely remove Al and exfoliate the MXene into the desired sheet structure. Nonetheless, these techniques still lead to -F functionalized MXenes which still need modification to afford their application in biomedical applications.

Fluoride-free synthesis routes have therefore emerged as promising alternatives, enabling the design of MXenes with tailored surface properties and helping to advance their suitability for biomedical applications (Vasyukova et al., 2022). One alternative approach involves using molten salts as the etchant (Li et al., 2019; Mehlawat et al., 2025; Yan et al., 2026; Iakunkov et al., 2025). This method is often applied to nitride-based MXenes to avoid the structural degradation commonly caused by fluoride-based etchants (Mehlawat et al., 2025). Li et al. (2019) synthesized Zn-MAX by reacting Al-MAX with Zinc chloride (ZnCl₂) at a molar ratio of 1:1.5, with the goal of substituting Al with Zn in the MAX phase. Their study demonstrated that metal halides with low melting points and strong Lewis acidity in the molten state can effectively drive the replacement reaction, enabling Al removal at moderate temperatures. This molten-salt strategy is considered a viable and greener synthetic route, offering potential for scalable MXene production and future commercial implementation. In addition, MXenes can also be terminated with unconventional surface groups such as -Cl, -Br, and -I by employing different molten salts (e.g., Copper chloride (CuCl₂), Copper bromide (CuBr₂), or Copper Iodate (CuI)) during the etching process (Kamysbayev et al., 2020). These halogen terminations can be readily removed through elimination or substitution reactions, allowing the introduction of desired surface functionalities. Kamysbayev et al. (2020) demonstrated the synthesis of MXenes bearing a wide range of surface terminations, including -Br, -Cl, -NH, -O, -S, -Se, and -Te, as well as termination-free MXenes, using a two-step reaction strategy. In the first step, MXenes functionalized with halogens such as Cl or Br were produced by treating the precursor with molten chlorine- or bromine-containing salts. Owing to the relatively weak metal-halide bonds, these halogen-terminated MXenes could then undergo a subsequent substitution reaction to introduce new surface groups, such as -O, -S, -NH, or -Se. This level of controllable surface functionalization, combined with precise size control, opens the possibility of tailoring MXenes with properties specifically suited for advanced applications in healthcare.

Acidic and alkaline treatments have also been explored as alternative etching routes for MXene synthesis (Mehlawat et al., 2025; Li et al., 2017). These methods avoid the challenges associated with HF etching and can introduce surface terminations beyond the typical–F groups. Li et al. (2017) demonstrated the use of potassium hydroxide to etch Ti₃AlC₂ and produce Ti₃C₂T_x. In their procedure, a mixture of Potassium hydroxide (KOH) and MAX powder was placed in an autoclave and heated at 180 °C for 24 h, followed by repeated washing with deionized water until a neutral pH of 7 was achieved. The resulting material was then dried in a vacuum oven at 60 °C for 12 h. In another study, MAX powder was treated with 27.5 M Sodium hydroxide (NaOH) and autoclaved at 270 °C for 72 h (Yoon et al., 2023). After thorough washing and removal of residual impurities, a stable NaOH-derived MXene colloid was obtained, as illustrated in Figure 3. The authors evaluated the cytotoxicity of this NaOH-MXene using HeLa cells. They reported that cell viability remained unchanged across a wide concentration range, from low doses up to 1,000 μg/mL and even at higher concentrations of 2000 μg/mL, indicating excellent biocompatibility. Moreover, the NaOH-derived MXene exhibited enhanced oxidative stability, retaining its structural integrity for up to 2 weeks under oxidative conditions. This suggests that adopting eco-friendly and sustainable synthesis routes for MXenes can broaden their potential for applications in biomedicine and therapeutics.

Yet another fluoride-free method is electrochemical etching, using HCl, NaCl and NH₄Cl, though it is limited by long processing times and low yields (Mehlawat et al., 2025). This scalable and safe method afforded particles with sizes up to 18.6 with a yield of >90% of monolayer and bilayers. In contrast, a more recent fluoride-free approach involving anodic corrosion of MAX phases in a binary aqueous electrolyte has shown promising results (Yang et al., 2018). This technique produces chloride ions for anodic Al removal, followed by ammonium hydroxide (NH₄OH) intercalation. The process has yielded MXene flakes as large as 18.6 µm with production yields exceeding 90%, and the resulting materials feature -OH and -O surface terminations instead of -F. Although the resulting surface terminations and yields are promising for medical applications, the field is still in its early stages with respect to consistent processability, and reliable control over key material properties such as mechanical strength, electrical conductivity, and electrochemical behaviour.

On the bottom-up side, chemical vapor deposition (CVD) has been demonstrated to produce MXenes of higher structural quality compared with many top-down methods (Shingange and Mokhena, 2026; Jiang et al., 2019). This technique eliminates the need for hazardous etching agents and prevents the generation of harmful waste. Since CVD relies on small molecules as precursors in crystal growth, it is well-known for producing high-quality materials. This technique enables the growth of single-layer MXenes and ultrathin films with precise thickness control (Jiang et al., 2019). Wang et al. (2023) demonstrated that CVD can be employed to synthesise Ti₂CCl₂ and Ti₂NCl₂ using titanium metal, TiCl₃ or TiCl₄, together with various carbon or nitrogen sources such as graphite, CH₄, and N₂. The resulting MXenes can be delaminated and subsequently functionalised through nucleophilic substitution or reductive elimination. This approach offers several advantages, including scalability, operational convenience, and the potential to synthesise materials that are otherwise challenging to obtain through conventional etching routes. Turker et al. (2020) investigated the effects of key CVD parameters, such as reaction time, reaction temperature, and substrate type. Their findings showed that Mo₂C crystals grown on graphene exhibit fewer defects and ultrathin thickness compared to those grown on copper substrates. This improvement is attributed to graphene serving as an additional diffusion barrier, limiting the migration of Mo atoms through the copper.

In summary, substantial progress has been made in advancing MXene synthesis from laboratory research to industrial-scale production, but there are few hurdles the negatively affect their biomedical application (Ding et al., 2026). Notably, top-down methods remain the most developed and are currently leading the transition toward commercial manufacturing of MXenes. These methods frequently leave behind toxic residues that are detrimental to biological systems and compromise biocompatibility. For example, fluoride-based etching can introduce fluorine-containing residues that are harmful and unsuitable for biomedical application (Vasyukova et al., 2022; Diedkova et al., 2025). Developing fluorine-free, environmentally friendly etching strategies would help minimise toxicity and improve safety for use in biomedical contexts. Besides, the surface functionalities of MXenes being the major determinant of their biocompatibility and thus their biomedical applications, other parameters were also reported to play a crucial role in dictating MXenes cytotoxicity (Vasyukova et al., 2022; Diedkova et al., 2025). For example, Diedkova et al. (2025) investigated the influence of etching and delamination on the biocompatibility of Ti-based MXenes. In their study, HF/HCl and HF/HCl/H₂O were used as etchants, while LiCl and NaCl served as intercalating agents. Selective etching yielded two MXene compositions, i.e., Ti₃C₂ and Ti₃C_1.5N_0.5. The authors reported that at low MXene concentrations (6.25 μg/mL), no cytotoxicity was observed; however, higher doses led to reduced cell viability regardless of MXene type or synthesis route. The cytotoxicity, however, was strongly influenced by MXene composition. Carbonitride MXene (Ti₃C_1.5N_0.5) demonstrated superior biocompatibility compared to its carbide counterpart (Ti₃C₂). This is a result of lower density of–F terminations in nitrogen-substituted MXenes. The etching method also had a significant effect. The inclusion of water in the HF/HCl etchant led to MXenes with improved biocompatibility relative to conventional HF/HCl-etched MXene. This enhancement was ascribed to the replacement of–F functionalities with–OH groups. Generally, MXenes etched with HF exhibit higher toxicity due to the release of F⁻/HF, unfavourable interactions with cell membranes, and increased hydrophobicity introduced by–F terminations compared to the more hydrophilic–OH groups (Ghidiu et al., 2014; Diedkova et al., 2025). On the other hand, Na⁺-intercalated MXenes exhibited negligible toxicity compared to Li⁺-intercalated ones (Diedkova et al., 2025). This was attributed to the disruptive effect of released Li⁺ ions on cellular ion homeostasis, whereas Na⁺ ions are more readily washed out or form a thicker hydration shell around the MXene surface, thereby improving biocompatibility. Beyond these factors, MXene particle size significantly influenced cytotoxic (Diedkova et al., 2025). Smaller particles (∼280 nm) exhibited better biocompatibility than larger ones (∼1-2 µm). The smaller particles remain suspended, achieve more uniform distribution, and ensure consistent exposure across cells. Overall, careful optimization of multiple parameters, including surface chemistry, synthesis route, intercalation strategy, and particle size, can substantially enhance the safety profile of MXenes, supporting their potential for integration into biomedical applications. In addition, MXenes are highly susceptible to oxidation when exposed to water or oxygen at ambient conditions. This process typically initiates at surface defects and edges. Therefore, careful control of synthesis parameters, such as temperature, etchant concentration, and etching duration, can help improve their resistance to oxidation. Nevertheless, the various synthetic routes available for producing MXenes endow them with a wide range of properties, including versatile surface chemistry, excellent electrical conductivity, tuneable electronic structures, and adjustable interlayer configurations, properties that collectively offer significant potential for biomedical applications.

Cellulose

In recent years, the search for new materials that combine advanced performance, and ecological awareness has reached unprecedented dimensions, and the development of sustainable and eco-friendly materials has become the leading trend in research and business today (Mitchell et al., 2021; Varma, 2019; Mokhena et al., 2024; Mphateng et al., 2025; Santhosh et al., 2024). The demands for materials whose role is not only to fulfil performance requirements but also to follow sustainability have continuously risen owing to the exponentially growing demand for energy storage, power generation, and sensing technologies (Singh et al., 2020). Thus, cellulose-based conductive materials have emerged as a highly promising family of materials which could become very important in the re-design of energy and sensor applications (Li et al., 2021). The availability and biodegradability of cellulose are becoming answers to environmental problems. They can be applied in a variety of flexible electronics sectors because of their exceptional performance. The demand for cellulose in the numerous domains of contemporary innovations is increased by exotic properties including high surface area, high porosity, superior interconnectivity, high biodegradability, low toxicity, and strong electric performance.

All plants are built on cellulose, which is the most common organic material found on Earth’s surface. As a result, it becomes widely available and reasonably priced. This organic material can naturally break down without endangering the environment because it is biodegradable (Moon et al., 2016; Mokhena and John, 2020a; Mokhena et al., 2021). Cellulose can be processed into different forms, such as fibers, films, gels, and paper, depending on the anticipated application. Despite its high tensile strength, the mechanical performance of cellulose is still inferior to that of many synthetic materials (Cui et al., 2019). This can be addressed by incorporating other materials such as fillers. However, this may compromise the decomposability of cellulose materials.

Condensation of β (1→4) glycosidic connections transforms D-glucose units into cellulose, a polysaccharide having the chemical formula (C₆H₁₀O₅)_n. Three hydroxyl (-OH) groups, one on the C2 carbon, one on the C3 carbon, and one on the C6 carbon, are joined to a glucose unit in the chemical structure of cellulose. The C1 carbon of one glucose unit and the C4 carbon of the adjacent glucose unit create the β (1→4) glycosidic bond. The β (1→4) glycosidic bond causes the glucose units in cellulose to be reversed 180° apart along the chain. This arrangement allows neighbouring chains to establish hydrogen bonds with one another (Moon et al., 2011; Ravindran et al., 2019).

The many hydroxyl groups on the glucose from one chain are able to lock the chain firmly in place by creating hydrogen bonds with oxygen atoms on either the same chain or a nearby chain. Cellulose has a strong and fibrous structure because of the straight, linear orientation of the repeated glucose units (Mokhena et al., 2021). In cellulose, there exist crystalline and amorphous fibrils. These microfibrils are made of several adjacent chains of cellulose that are joined by hydrogen bonds. Then, the microfibrils themselves can come together to form even larger structures, i.e., cellulose fibers, which give strength and rigidity to plant cell walls. The extensive hydrogen-bonding network in cellulose also limits its processability, as it renders the material difficult to dissolve in most common solvents (Cui et al., 2019). Consequently, chemical modification of cellulose into its derivatives has become a widely used strategy to enhance solubility and improve processing and thus offering improved processability through a different route. Alternatively, cellulose can be converted into nanocellulose, which possesses a high surface area and excellent mechanical properties (Ilyas et al., 2018; Ilyas et al., 2019; Agbakoba et al., 2023; Mokhena and John, 2020b). Nanocellulose can be classified into cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs), depending on the isolation technique employed. Furthermore, it may be categorized based on its biological source, including bacterial (BC), algal (AC), plant, and animal-derived cellulose (Mokhena and John, 2020a; Mokhena et al., 2021). To avoid ambiguity, all cellulose-based materials, regardless of their source or dimensions, will be referred to collectively as cellulose, unless otherwise specified.

When combined, the abovementioned characteristics of cellulose, together with the unique properties of MXenes, enable the fabrication of composites with enhanced overall performance. In particular, the inherent limitations of cellulose, such as its low thermal and electrical conductivity, can be effectively addressed through the incorporation of MXene, thereby broadening the range of potential applications, especially in the healthcare sector (Ilyas et al., 2018; Ahmed et al., 2021).

Preparation methods for MXene-cellulose composites

Different types of cellulose and MXene possess unique physical properties and surface functionalities that influence their compatibility and the resultant structural evolution during composite preparation. For instance, the use of cellulose nanofibers with flexible fibers allows stacking during vacuum filtration and thus the resultant material can be used in flexible wearable sensors. On the other hand, bacterial cellulose with 3D interconnected pores resulting from bacterial biosynthesis provides exceptional pore continuity and mechanical strength when used in solution casting, and vacuum filtration. MXene is characterized by its inherent hydrophilicity making it readily disperses in aqueous medium and thus suitable for vacuum filtration, and solution casting. Table 1 summarizes some studies that are based on fabrication of MXene-cellulose composites (Zhou et al., 2020; Cao et al., 2018; Zhan et al., 2019; Ma et al., 2021; Liu et al., 2022; Shang et al., 2021).

TABLE 1. Summary of studies on MXene-cellulose fabrication.

Vacuum filtration is one of the widely used techniques for fabricating MXene-cellulose composites (Song et al., 2020; Oliveira et al., 2023; Wang et al., 2022; Feng et al., 2022). This process involves driving an aqueous dispersion of the components through a membrane under applied pressure, forming compact and well-ordered multilayer structures. This method is commonly employed when working with CNCs, CNFs, BC, and MXene. To ensure proper dispersion of cellulose and MXene, sonication is often applied prior to filtration, and the filtration rate is carefully controlled to achieve the desired compactness and strong interfacial interactions between the components. Numerous studies have demonstrated the effectiveness of vacuum filtration in producing composites with tailored properties for specific applications. This method is highly attractive due to its practicality in producing micrometer-thick, flexible, and scalable films suitable for wearable devices. These films can be folded and bent without compromising their electrical conductivity. For example, Feng et al. (2022) fabricated MXene-cellulose composites using a one-pot milling process. In this method, a MXene-CNF hybrid slurry was generated through intense shear forces applied by a Supermass Collider grinder (MKCA6-2, Masuko Sangyo Co., Ltd., Japan), resulting in exfoliated MXene uniformly dispersed within cellulose fibrils. Subsequent vacuum filtration of the slurry produced films with remarkable improvements in mechanical properties, approximately a 1,388% increase, and electrical conductivity, which rose by about 3,726%. Additionally, the resulting films exhibited exceptional flexibility and foldability, making them highly suitable for advanced applications, such as wearable sensors for health monitoring.

Layer-by-layer self-assembly enables the formation of uniform, continuous layered composites through alternating deposition cycles (Shang et al., 2021; Ran et al., 2023; Li et al., 2026; Kumari et al., 2021; Hu et al., 2021). Strong interactions between cellulose and MXene allow the fabrication of composites with enhanced physicochemical properties. The hydrophilic nature of both components facilitates the dispersion of MXene within cellulose, which serves as the host polymeric material. Li et al. (2026) employed a vacuum filtration process to fabricate a self-assembled hierarchical MXene-cellulose composite film. In their approach, MXene was modified using Polyethylenimine (PEI) and dopamine (DA), then deposited onto a cellulose film via filtration to achieve flexible films with superior mechanical properties. The cellulose film itself was prepared through a similar filtration process. Ma et al. (2022) employed a vacuum filtration technique followed by post-treatment, repeating the process to achieve a self-assembled film, as illustrated in Figure 4. Scanning electron microscope (SEM) analysis revealed that MXene and cellulose were uniformly integrated without distinct boundaries, indicating the formation of gradient composites. Furthermore, energy dispersive X-ray spectroscopy (EDS) mapping confirmed the presence of all expected elements, with Ti from MXene displaying a light-to-dark gradient from top to bottom, signifying successful layer-by-layer construction through sequential vacuum filtration. The resulting films demonstrated excellent mechanical performance along with good electrical conductivity. This approach is favoured for creating thin, flexible, and mechanically strong coatings or free-standing films with high electrical conductivity and tuneable surface properties suitable in biomedical applications such as tissue engineering, wound healing, and biosensing.

Casting is one of the commonly preferred techniques for fabricating MXene-cellulose composites (Oliveira et al., 2023). In this approach, MXene is dispersed with cellulose to form a homogeneous solution, which is then cast onto a substrate and allowed to dry through solvent evaporation under natural or controlled conditions. This method is particularly suitable for preparing MXene composites with CNFs, CNCs, BC suspensions. The gradual evaporation of the solvent provides sufficient time for component rearrangement and the formation of hydrogen bonds between MXene and cellulose, resulting in dense, uniform, and flexible films. This method often produces materials with superior mechanical properties compared to those obtained through vacuum filtration (Martín-Sampedro et al., 2025). Typically, the MXene content incorporated into the composite ranges from 0 to 90 wt%. For example, Wu et al. (2023) prepared MXene-CNCs composites at varying cellulose ratios by casting the mixed suspension into a propylene mold and drying it at 50 °C, producing freestanding films with high conductivity and excellent flexibility. Their study reported that 50% CNCs was the optimal content for achieving superior tensile strength, modulus, and toughness compared to neat MXene films. However, further increases in CNC content led to a decline in mechanical performance due to compromised interfacial adhesion between MXene and excess CNCs. This demonstrates that the composition of both components can be tailored to meet specific application requirements using the solution casting method. The main challenge with this approach, however, lies in its scalability for industrial production.

Coating represents another effective strategy for fabricating MXene-cellulose composite materials (Li et al., 2020). In this approach, the target substrate is immersed in an MXene-cellulose suspension to ensure surface deposition. This offer advantage of MXene-cellulose located on the surface of the substrate and thus the accessibility to targeted reactants. Since large amount of MXene-cellulose can be loaded onto the substrates the resultant composites have a large surface area and high adsorption capacity making them suitable for health monitoring purposes and wound dressing. For example, Li et al. (2020) employed a simple dip-coating technique to coat thermoplastic polyurethane (TPU) nonwoven fabrics with MXene-CNCs. The nonwoven fabrics were cut into the desired shapes and then immersed in the MXene-CNCs suspension under sonication for 20 min. Afterward, the coated fabrics were dried at 50 °C for 1 hour. The hydrogen bonds between TPU and MXene-CNCs promote strong interfacial adhesion between the components, which is crucial for the electrical and sensing properties of the resulting sensor. With a broad sensing range of ∼83%, high sensitivity (GF = 3,405), and an ultrahigh detection limit of 0.1%, the sensor’s performance relies on controlled crack density achieved through optimization of the coated layer. These preparation methods are particularly valuable for sensor development, as they enable optimization of the coating materials while retaining the intrinsic properties of the substrate. This results in composites with excellent mechanical properties and strong interfacial contact, which is crucial for their intended applications. Bu et al. (2021) also showed that dip-coating is an effective and practical technique for fabricating ultrasensitive sensors for human motion detection and electronic skin (E-skin) applications. In their approach, a mixture of MXene and CNCs was used as the coating material, into which printing paper was immersed and subsequently dried. Hydrophobicity of the resulting composite was introduced by briefly exposing the material to a candle flame, allowing candle soot to deposit on the surface. This treatment generated microcracks that played a key role in enabling the desired sensing performance. Overall, coating is a low-cost and easily scalable method for producing MXene-cellulose composites. However, its main limitation is that the coating parameters must be carefully optimized to achieve the desired material properties (Li et al., 2020; Bu et al., 2021).

MXene has been widely investigated as a conductive filler for fabricating conductive hydrogels (Al-Fakih et al., 2024; Pi et al., 2021; Yang M. et al., 2025; Zhang et al., 2025; Mao et al., 2020). However, the resulting composites often exhibit low mechanical strength due to MXene agglomeration, which remains a major limitation for their practical applications despite their excellent electrical conductivity. Incorporating cellulose significantly improves MXene dispersion while enhancing the overall strength of the hydrogel. Beyond this, cellulose and its derivatives have also been widely utilized as primary components in hydrogel systems, either through appropriate crosslinking or as additives in polymer-based hydrogels (Zhang et al., 2025; Zhao et al., 2021). Their inclusion imparts unique benefits such as improved adsorption capacity, mechanical robustness, thermal stability, barrier properties, and moisturizing effects, owing to the distinctive characteristics of cellulose. Pi et al. (2021) developed an MXene-based ultrasensitive hydrogel sensor by integrating CNCs through in situ polymerization and freeze-drying. Acrylamide was polymerized within a Polyvinyl acetate (PVA) solution, followed by the introduction of an MXene-CNCs suspension, resulting in a tough, fatigue-resistant, and highly conductive hydrogel suitable for strain sensors in movement monitoring.

The in-situ incorporation of various nanoparticles into MXene-cellulose composites has been widely explored to expand their functional applications (Al-Fakih et al., 2024; Zhan et al., 2021). For instance, Zhan et al. (2021) synthesized SiO₂ nanoparticles anchored onto delaminated MXene using a sol-gel approach. Tetraethyl orthosilicate (TEOS) served as the precursor, enabling the growth of SiO₂ nanoparticles within the MXene structure. These were then introduced into a CNF suspension to form hybrid composite films. The resulting suspension was filtered through a cellulose ester membrane using vacuum-assisted filtration and subsequently dried overnight in a vacuum oven at 60 °C. This process highlights the ease with which additional components can be integrated into MXene-cellulose composites, paving the way for multifunctional materials with potential healthcare applications.

Comparison between MXene-cellulose fabrication methods

The performance of MXene-cellulose composites largely depends on their composition, the intrinsic properties of the individual constituents, and the nanoarchitecture of the final material. To develop composites suitable for healthcare applications that exceed expectations, research efforts have focused on integrating MXene with cellulose and other biocompatible components to ensure safety and avoid harmful byproducts. Consequently, various fabrication methods, such as those discussed earlier, have been adopted for their simplicity, effectiveness, and efficiency in producing materials with tailored properties. Table 2 provides a comparative summary of these techniques, highlighting their respective advantages and limitations (Al-Fakih et al., 2024; Song et al., 2020; Ran et al., 2023; Li et al., 2020; Fan et al., 2023).

TABLE 2. Comparative analysis of MXene-cellulose composite fabrication methods.

In summary, pristine MXene-based films exhibit poor mechanical properties, with tensile strength around 9.7 MPa, elongation at break of approximately 1.0%, and a modulus near 0.95 GPa, which significantly limits their use in applications such as wearable devices. While different fabrication methods yield varying mechanical performances, incorporating polymers has proven effective in enhancing these properties. Specifically, cellulose as a host polymer offers strong interfacial interactions with MXene due to their shared hydrophilic nature, forming robust interconnected networks through hydrogen bonding. Among the available techniques, solvent evaporation stands out, as it provides sufficient time for structural rearrangement and network formation, resulting in composites with superior mechanical integrity. It can be argued that the scalability of fabrication methods, along with their environmental and economic impacts, should serve as a baseline for selecting the most appropriate approach. In alignment with the United Nations Sustainable Development Goals (SDGs), particularly SDG 9 (Industry, Innovation, and Infrastructure), SDG 12 (Responsible Consumption and Production), and SDG 13 (Climate Action), future research must prioritize techniques that minimize energy consumption, reduce waste, and utilize renewable or biodegradable materials. Developing green, cost-effective, and industrially scalable processes will be critical for transitioning MXene-cellulose composites from laboratory-scale innovation to real-world applications such as wearable electronics and sustainable energy devices. Furthermore, integrating life-cycle assessments and circular economy principles into material design will ensure that these advanced composites contribute to a more sustainable technological future. It can be concluded that the preparation method for MXene–cellulose composites is closely dictated by the intended healthcare application, as each method results in materials with distinct properties. It is also important to note that further optimization of these preparation techniques is still required to achieve the desired functional performance for specific applications.

Wound dressing

Electrical stimulation (ES) dressings have emerged as promising solutions for promoting wound healing, particularly in the management of chronic wounds. However, conventional ES systems often rely on external power sources or involve complex structural designs, which can introduce safety risks and create practical inconveniences during use (Yang S. B. et al., 2025; Shi et al., 2025; Kai et al., 2017; Yan et al., 2025; Maleki et al., 2022). This has led to a growing need for safe, simple, and self-powered ES dressings that can deliver therapeutic benefits without these limitations. To address this challenge, researchers are exploring electroactive wound dressings capable of responding to physiological electrical signals or external stimulation at the wound site throughout the healing process (Yang S. B. et al., 2025; Shi et al., 2025; Kai et al., 2017; Yan et al., 2025). Among the materials under investigation, MXenes stand out due to their exceptional electrical conductivity, hydrophilicity, mechanical robustness, and biocompatibility (Mao et al., 2020; Maleki et al., 2022; Wang C. et al., 2026; Davlet et al., 2025). When combined with cellulose, a material known for its high-water absorption, excellent mechanical strength, permeability, biodegradability, and biocompatibility, the result is a composite with highly desirable properties for wound care applications (Mao et al., 2020; Davlet et al., 2025).

A notable development in this area is a biodegradable hydrogel composed of Ti₃C₂T_x MXene and BC, designed as an electroactive wound dressing for chronic wound treatment (Mao et al., 2020). This hydrogel demonstrates outstanding mechanical strength, flexibility, and recoverability, largely attributed to the reinforcing effect of MXene and the strong interactions between MXene and cellulose. These interactions occur through van der Waals forces and hydrogen bonding, facilitated by MXenes’ terminal groups (-F, -O, and -OH) and the abundant hydroxyl groups on the cellulose surface. Such structural synergy makes the hydrogel an ideal candidate for wound dressing applications. The hydrogel exhibits tuneable electrical conductivity, ranging from 2.8 × 10⁻⁵ to 7.0 × 10⁻⁴ S/cm, depending on the MXene content within the hybrid system. When combined with external electrical stimulation, the hydrogel and ES work synergistically to enhance the proliferation of NIH3T3 cells in vitro and actively accelerate the wound healing process in vivo. This innovation represents a significant step toward developing advanced, multifunctional wound dressings that integrate biocompatibility, biodegradability, and electroactivity for improved therapeutic outcomes.

A sponge composed of BC and MXene was recently reported as a dressing material for programmed diabetic wound healing (Chen L. et al., 2025). This sponge mimics the extracellular matrix microenvironment and provides dynamic immune modulation at the wound site. The incorporation of MXene enhances the electrical conductivity of the dressing, promoting the generation and transfer of endogenous electric fields to the skin tissue, thereby accelerating the healing process. In addition to its conductive properties, the sponge exhibits antibacterial activity through photothermal conversion, and supports key healing mechanisms such as granulation tissue formation, collagen deposition, angiogenesis, and re-epithelialization, with all observed within a 14-day period.

Elsewhere, a hybrid hydrogel composed of BC and MXene was prepared and chemically crosslinked using epichlorohydrin (Dang et al., 2024), followed by physical crosslinking with ethanol (lIhan et al., 2025). Compared to neat BC hydrogel, the hybrid demonstrated superior mechanical strength and water absorption capacity, reaching 300%–320% depending on MXene content. Among the tested formulations, the hydrogel containing 2% MXene exhibited the best overall performance in terms of electrical conductivity, mechanical properties, water uptake, and biocompatibility, making it suitable for application as a “skin patch” in healthcare. Interestingly, the 1% MXene hybrid showed the highest cell viability from day 3 to day 7 (Figure 5A). Similarly, cell adhesion was significantly greater for the 1% hybrid compared to BC, tissue culture plastic (TCP), and the 2% hybrid (Figure 5B). Hemolysis ratios of 0.09, 0.86, and 1.49 for BC, 1%, and 2% hybrids, respectively, confirmed excellent blood compatibility with no hemolytic activity across all samples. These findings highlight the potential of MXene-cellulose hybrids as multifunctional wound dressings combining biocompatibility, electroactivity, and structural integrity. However, it was reported that MXene negatively affected cell proliferation. Such effect can be mitigated by incorporating cellulose. Therefore, it is essential to optimize the MXene concentration to ensure that cellular growth and proliferation are not compromised.

Wang J. et al. (2026) developed a sprayable MXene/carboxymethyl cellulose (CMC)/pectin hydrogel with enhanced photothermal antibacterial activity and strong antioxidant properties for wound dressing applications. In this design, CMC was functionalized with DA and hydrazine groups while oxidized pectin was incorporated to improve spraying ability, tissue adhesion, and antioxidant performance. The inclusion of MXene significantly improved the hydrogel’s photothermal antibacterial capability. Additionally, tranexamic acid (TXA) was loaded into the composite to reduce blood loss and promote full-thickness skin wound repair. Histological analysis and immunofluorescence staining revealed that the hydrogel accelerated skin regeneration, reduced inflammatory responses, and upregulated Vascular endothelial growth factor (VEGF) expression, demonstrating its potential for effective full-thickness wound healing.

Therefore, it can be argued that the integration of cellulose and MXene offers a unique opportunity to design advanced wound dressings that maintain an optimal microenvironment for healing. Such dressings can provide balanced moisture, support cellular proliferation, and exhibit electroactive properties that actively promote tissue regeneration. Achieving these characteristics depends on selecting appropriate processing methods and adjusting the composition of MXene and cellulose to tailor properties critical for wound healing.

Sensors

Motion and strain sensors are essential tools for detecting electrical signals generated by mechanical deformations (Ni et al., 2024; Hakim et al., 2025; Cao et al., 2022; Huang et al., 2025). These sensors are widely applied in wearable devices, healthcare monitoring systems, and soft robotics. Their operating principle involves converting mechanical changes, such as stretching, bending, and compression, into electrical signals that can be used to monitor physical movements. One of the major challenges in designing strain sensors is achieving high detection capability without compromising sensitivity, durability, or long-term stability. Incorporating nanostructured materials, such as MXenes, offers a promising solution by enhancing detection performance while maintaining other critical properties (Ni et al., 2024; Hakim et al., 2025; Cao et al., 2022). For example, a conductive hydrogel with excellent electrical conductivity and adaptable mechanical properties was developed by combining MXene with quaternized CNFs for use as a flexible strain sensor (Ni et al., 2024). By adjusting the composition, the mechanical properties can be fine-tuned without sacrificing conductivity. The resulting hydrogel exhibited impressive characteristics, including a tensile strength of 449 kPa, exceptional stretchability exceeding 1700%, and ultrahigh toughness of 5.46 mJ m^-3. These properties are attributed to its interconnected structure formed through strong macromolecular interactions and the nano-reinforcing effect of MXene. With high conductivity, the hydrogel demonstrated remarkable sensitivity, achieving a gauge factor of 2.24 across a wide working range (0%–1,465%) and fast response times, 141 m for response and 140 m for recovery. These features make it suitable for monitoring multiscale deformations, from large repetitive movements to subtle physiological motions such as joint activity, signature recognition, and even vocal patterns. Shayan et al. (2025) developed a strain sensor by integrating MXene and CNCs with Polydimethylsiloxane (PDMS). To overcome phase separation between hydrophilic MXene and cellulose nanofibers, the two components were first mixed and freeze-dried to form a 3D porous structure, which was then immersed in PDMS (as shown in Figure 6). The resulting hybrid exhibited a tensile strength of 400 ± 24 kPa and a maximum gauge factor of approximately 3, making it suitable for strain-sensing applications. When the hybrid film was affixed to a human finger, bending caused the film to stretch, increasing the distance between conductive MXene sheets and thereby raising the resistance. Conversely, relaxing the finger brought the MXene sheets closer together, reducing resistance. These changes during bending and relaxation were clearly detected by the sensor, with an 8% variation in resistance, demonstrating its effectiveness for monitoring small mechanical deformations, critical for wearable devices and healthcare monitoring systems. Additionally, the film maintained high stability over 300 cycles of dynamic tension at 5% strain and exhibited excellent thermal stability, making it suitable for use in dynamic and high-temperature environments.

Liu et al. (2022) developed a highly sensitive, multifunctional electronic skin based on MXene-TEMPO-oxidized CNFs using a vacuum-assisted filtration method. The resulting film exhibited outstanding mechanical strength (∼125 MPa), exceptional electromagnetic shielding performance (36 dB), as well as antibacterial properties and biocompatibility. The composite demonstrated high sensitivity, rapid response and recovery times of less than 10 m, an ultralow detection limit of 0.2 Pa, and long-term durability over 10,000 cycles. Furthermore, the device showed excellent capability in monitoring various human activities, including finger bending, chewing, and diverse facial expressions.

A hydrogel-based strain sensor was fabricated using electrohydrodynamic printing combined with ultraviolet photopolymerization, achieving high stretchability, a broad sensing range, and excellent sensitivity (Huang et al., 2025). The hydrogel formulation included sodium alginate, CNCs, and acrylamide, integrated with cracked MXene film prepared via vacuum filtration, and subsequently cured under UV light. To ensure optimal sensor performance, the hydrogel was pre-stretched at varying strain levels (0%, 60%, 80%, and 100%). The resulting sensor exhibited outstanding detection capabilities in the low-strain range (0%–5%), with a gauge factor of 23.4, a rapid response time of 106 m, and a recovery time of 82 m. These properties make the sensor highly suitable for applications such as human motion monitoring, minor vibration detection, and smart wearable electronics for health rehabilitation.

Current challenges with MXene

MXene oxidation

The issue of MXene oxidation is still one of the most serious challenges for long-term biomedical applications. Although MXenes show promise, there are still concerns regarding their chemical stability. Ti₃C₂Tx MXenes are known to oxidize with time, despite the fact that many studies do not mention this. As a result, Ti₃C₂Tx (and other MXenes) are becoming less useful in some applications. This issue has only been briefly examined in the past, and strategies for stopping or postponing the oxidation of MXenes are currently poorly known.

There have been a few reports on mitigation methods. By adjusting the heating rate, temperature range, and exposure time, Ghassemi et al. (2014) demonstrated how to control the oxidation of Ti₃C₂Tx MXenes in air to produce TiO₂. They found that anatase TiO₂ particles are formed by high heating rates, while rutile TiO₂ particles are produced by moderate heating rates.

Ti₃C₂Tx oxidation behavior in air, liquid, and solid media was evaluated by Habib et al. (2019). They found that the oxidation is fastest in liquid medium and slowest in solid media. Contrary to earlier reports, the data indicates that the black color and colloidal stability of the dispersion are not accurate markers of oxidation. Ti₃C₂Tx oxidizes in water within 2 weeks. In terms of storage, Ti₃C₂Tx can be freeze dried to create a re-dispersible powder or kept in ice (and to a lesser extent in some organic solvents) to reduce oxidation. Regardless of the polymer content, Ti₃C₂Tx composites show comparable patterns in terms of conductivity decline, indicating that the polymer does not function as a barrier to reduce oxidation (lIhan et al., 2025).

A composite combining MXene and TEMPO-oxidized cellulose nanofibers (TOCNFs) made from tunicate and tannic acid (TA) was described in the work by Lee et al. (2025). Because of the high crystallinity of tunicate, TOCNFs has a high mechanical strength, and TEMPO-mediated oxidation introduces carboxyl groups that promote interfacial interaction with MXene layers. MXene and TOCNFs are further integrated by strong hydrogen bonding by TA, a naturally occurring polyphenol with exceptional oxidation resistance. While retaining good electrical conductivity (81.4 S/cm), the produced MXene/TA/TOCNFs composite showed noticeably enhanced mechanical strength of 98.3 MPa and oxidation resistance. The potential of MXene/TA/TOCNFs for energy storage devices and flexible electronic applications is highlighted by this cooperative integration of TA and TOCNFs (Wang J. et al., 2026).

Mxene cytotoxicity

Reactive oxygen species (ROS) generation remains one of the most consistently reported mechanisms underlying MXene-associated cytotoxicity and therefore represents a central consideration in risk assessment. Studies involving Ti₃C₂T_x and related MXenes demonstrate concentration- and exposure-time-dependent increases in intracellular ROS following cellular uptake and lysosomal localization (Ni et al., 2024; Hakim et al., 2025; Cao et al., 2022). Structural attributes such as lattice defects, sharp flake edges, and partially oxidized titanium sites may promote redox cycling reactions capable of overwhelming endogenous antioxidant systems (Huang et al., 2025). Excess ROS disrupts mitochondrial membrane potential, promotes lipid peroxidation, and induces DNA damage, ultimately activating apoptotic or necrotic pathways (Hakim et al., 2025; Ghassemi et al., 2014). Importantly, ROS induction is frequently negligible at low exposure levels, suggesting the existence of material and cell-specific biological thresholds below which oxidative stress responses remain manageable (Cao et al., 2022). From a safety perspective, this threshold behaviour highlights the importance of exposure control and dosage optimization rather than categorizing MXenes as intrinsically cytotoxic materials.

Dose dependence and cell specificity further complicate toxicity evaluation. Short-term in vitro and in vito assays, including 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay (MTT), Cell Counting Kit-8 (CCK-8), and Live/Dead staining, frequently report high cell viability (>80–90%) at concentrations below approximately 10–20 μg/mL, whereas higher doses are associated with reduced proliferation, compromised membrane integrity, and increased cell death (Cao et al., 2022; Habib et al., 2019). Immune cells such as macrophages and monocytes often exhibit enhanced sensitivity relative to fibroblasts or epithelial cells due to greater uptake and phagocytic activity (Lee et al., 2025). These observations indicate that biological outcomes depend strongly on administered dose, exposure duration, uptake kinetics, and the cellular microenvironment. Consequently, risk mitigation should emphasize controlling dispersion stability, limiting aggregation-induced local dose amplification, and carefully defining therapeutic or environmental exposure windows. Engineering strategies such as particle size optimization, removal of synthesis by-products, and improved colloidal stabilization in physiological media may reduce unintended cellular accumulation and associated toxicity beyond conventional surface functionalization approaches (Jastrzębska et al., 2017; Lim et al., 2021).

In addition to direct cytotoxicity, MXenes may activate inflammatory signalling pathways, particularly in immune-competent cells. Upregulation of pro-inflammatory cytokines including tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) has been observed at elevated concentrations or prolonged exposure durations in macrophage models (Lee et al., 2025; Wang et al., 2025; Browning et al., 2021). These responses are frequently linked to ROS production, lysosomal destabilization, and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) or inflammasome pathways (Wang et al., 2025). While low-dose exposure often produces mild or transient signalling suggestive of adaptive immune activation rather than pathological inflammation, uncertainty remains regarding long-term in vivo consequences. Risk mitigation therefore extends beyond chemical modification of MXene surfaces to include exposure-duration control, targeted delivery strategies that minimize off-target immune cell interaction, and incorporation of antioxidant or anti-inflammatory co-therapies where biomedical applications are intended (Li et al., 2023; Huang et al., 2020).

Material degradation introduces an additional dimension to biosafety evaluation. MXenes are chemically active and gradually oxidize under physiological conditions, generating soluble ionic species, hydroxides, and metal oxides such as TiO₂ (Malina et al., 2024; Nain et al., 2025). Controlled degradation may enhance clearance and reduce long-term accumulation risks (Ma et al., 2020). However, secondary products, including oxide nanoparticles or released metal ions, may induce delayed oxidative stress or inflammatory responses not captured by short-term assays (Malina et al., 2024). Risk management should therefore incorporate storage and processing strategies that minimize premature oxidation, environmental control of oxygen and moisture exposure during fabrication, and systematic characterization of degradation kinetics under physiologically relevant conditions (Ramezani Farani et al., 2026). Evaluating both parent materials and transformation products is essential for realistic long-term hazard assessment.

Short-term in vitro and in vito testing remains indispensable for mechanistic screening, enabling controlled investigation of cytotoxicity, oxidative stress, membrane disruption, genotoxicity, and early inflammatory signalling (Soomro et al., 2023). These studies provide valuable insight into dose response relationships, cellular susceptibility, and the influence of physicochemical parameters such as lateral size, thickness, oxidation state, and surface termination on cellular uptake. Nevertheless, conventional cell culture systems oversimplify biological complexity and fail to capture protein corona formation, immune modulation, vascular transport, metabolic transformation, and clearance mechanisms that strongly influence nanomaterial behaviour in vitro and in vito (Nain et al., 2025). Limited exposure duration further restricts the ability to detect cumulative or adaptive responses associated with repeated or chronic exposure.

In contrast, available in-vivo investigations generally report low acute toxicity, minimal haematological abnormalities, and limited histopathological damage at moderate doses, supporting preliminary biocompatibility for several MXene formulations (Cao et al., 2022; Nain et al., 2025; Ma et al., 2020). However, the current body of evidence remains limited by short observation periods, restricted dose ranges, and inconsistent experimental protocols. Key uncertainties persist regarding biodistribution, retention within reticuloendothelial organs, degradation pathways, immune modulation, and potential chronic inflammation. Addressing these knowledge gaps will require standardized exposure frameworks and extended follow-up studies capable of capturing delayed biological responses.

Overall, MXene cytotoxicity should be interpreted within a structured risk-assessment framework emphasizing exposure thresholds, physicochemical stability, and biological context rather than intrinsic material hazard alone. While in vitro and in vito studies provide essential mechanistic insight, their predictive value for long-term outcomes remains limited (Maleki et al., 2022; Guéguen et al., 2019). Future mitigation strategies should therefore combine improved material engineering (e.g., defect control and purification), dispersion and dose optimization, antioxidant co-interventions, and advanced predictive testing platforms such as 3D cultures and organ-on-chip systems alongside systematic long-term in vitro and in vito investigations. Such integrated approaches will be critical for establishing translational safety guidelines and enabling responsible deployment of MXenes in biomedical and other applications.

Future outlook

Future research should prioritize green and scalable synthesis routes for MXenes, minimizing the use of harsh etchants and reducing environmental impact. Developing cost-effective, energy-efficient fabrication techniques, such as continuous casting or roll-to-roll processing, will be crucial for industrial-scale production. From an application perspective, integrating smart functionalities such as self-healing, antibacterial properties, and real-time sensing into MXene–cellulose composites can expand their utility in personalized healthcare. Combining these materials with other bio-derived polymers or nanoparticles may further enhance performance, enabling multifunctional platforms for wound care, wearable electronics, and implantable devices. Additionally, life-cycle assessments and circular economy principles should guide future material design to ensure sustainability. Exploring biodegradable MXene derivatives, improving long-term stability in physiological environments, and conducting in vivo studies will be key steps toward clinical translation. Ultimately, interdisciplinary collaboration between materials science, biomedical engineering, and healthcare sectors will accelerate the development of MXene-cellulose composites as safe, effective, and sustainable solutions for modern healthcare challenges.

Conclusion

This review highlights recent advancements in MXene-cellulose composites for healthcare applications, with particular emphasis on wound healing and movement monitoring. It provides an overview of MXene synthesis strategies relevant to biomedical use and discusses composite preparation methods, including their advantages and limitations. It is anticipated that, as research continues to explore new approaches for enhancing the overall performance of MXene-cellulose composites, the insights presented in this review will make a meaningful contribution to the field. In conclusion, MXene–cellulose composites represent a promising class of materials for next-generation healthcare technologies. Nevertheless, several challenges must be addressed to further improve their suitability for biomedical use and to support their transition from laboratory research to clinical testing or practical deployment. Key limitations and potential solutions include the following:

First, the use of diverse synthetic routes for producing MXenes has resulted in significant batch-to-batch variability, as researchers frequently develop independent preparation methods. Such variability hinders the establishment of reliable comparison studies, which are essential for accelerating the clinical translation of MXene-based materials. There is therefore a need for greener, standardized, and scalable synthesis protocols that ensure consistent MXene quality and reproducibility.

Second, MXenes may exhibit limited biocompatibility owing to factors such as surface terminations, particle size, and the potential generation of ROS. Tailored surface modification and careful optimization of the final composite properties—based on the intended biomedical application—offer viable pathways to mitigate these concerns.

Importantly, the combination of MXenes with cellulose provides a unique synergistic advantage. MXenes contribute exceptional electrical conductivity and tunable surface chemistry, while cellulose offers biocompatibility, renewability, and mechanical reinforcement. This integration has enabled notable progress in multifunctional healthcare materials, particularly for wound dressings and human motion monitoring, where electroactivity, flexibility, and mechanical stability are critical.

While these developments are encouraging, comprehensive in vitro and in vivo studies are essential to evaluate the long-term biological safety and performance of MXene-cellulose composites. Such investigations will be crucial for expanding their applicability within the healthcare sector (Diedkova et al., 2025; Pourkhatoun et al., 2022; Lee et al., 2024; Wu et al., 2022; Monopoli et al., 2012; Kumari et al., 2024; Low et al., 2014; Ziemba, 2025).

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Footnotes

Edited by: Ajay Kumar Mishra, University of the Western Cape, South Africa

Reviewed by: Seyyed Mehdi Khoshfetrat, Ayatolah Borujerdei University, Iran

Huda M. Younis, University of Basrah, College of Dentistry, Iraq