Stimuli-responsive Hydrogels Research Articles

Fabrication of Functional Polymers with Gradual Release of a Bioactive Precursor for Agricultural Applications

Biodegradable and biocompatible polymeric materials and stimulus-responsive hydrogels are widely used in the pharmaceutical, agricultural, biomedical, and consumer sectors. The effectiveness of these formulations depends significantly on the appropriate selection of polymer support. Through chemical or enzymatic hydrolysis, these materials can gradually release bioactive agents, enabling controlled drug release. The objective of this work is to synthesize, characterize, and apply two controlled-release polymeric systems, focusing on the release of a phyto-pharmaceutical agent (herbicide) at varying pH levels. The copolymers were synthesized via free radical polymerization in solution, utilizing tetrahydrofuran (THF) as the organic solvent and benzoyl peroxide (BPO) as the initiator, without the use of a cross-linking agent. Initially, the herbicide was grafted onto the polymeric chains, and its release was subsequently tested across different pH environments in a heterogeneous phase using an ultrafiltration (UF) system. The development of these two controlled-release polymer systems aimed to measure the herbicide’s release across different pH levels. The goal is to adapt these materials for agricultural use, enhancing soil quality and promoting efficient water usage in farming practices. The results indicate that the release of the herbicide from the conjugate systems exceeded 90% of the bioactive compound after 8 days at pH 10 for both systems. Furthermore, the two polymeric systems demonstrated first-order kinetics for herbicide release in aqueous solutions at different pH levels. The kinetic constant was found to be higher at pH 7 and 10 compared to pH 3. These synthetic hydrogels are recognized as functional polymers suitable for the sustained release of herbicides in agricultural applications.

Environmental and Wastewater Treatment Applications of Stimulus-Responsive Hydrogels.

Stimulus-responsive hydrogels have emerged as versatile materials for environmental and wastewater treatment applications due to their ability to adapt to changing environmental conditions. This review highlights recent advances in the design, synthesis, and functionalization of such hydrogels, focusing on their environmental applications. Various synthesis techniques, including radical polymerization, grafting, and copolymerization, enable the development of hydrogels with tailored properties such as enhanced adsorption capacity, selectivity, and reusability. The incorporation of nanoparticles and bio-based polymers further improves their structural integrity and pollutant removal efficiency. Key mechanisms such as adsorption, ion exchange, and photodegradation are discussed, emphasizing their roles in removing heavy metals, dyes, and organic pollutants from wastewater. Additionally, this review presents the potential of hydrogels for oil-water separation, pathogen control, and future sustainability through integration into circular economy frameworks. The adaptability, cost-effectiveness, and eco-friendliness of these hydrogels make them promising candidates for large-scale environmental remediation.

Three-Dimensional Printable Magnetic Hydrogels with Adjustable Stiffness and Adhesion for Magnetic Actuation and Magnetic Hyperthermia Applications.

Stimuli-responsive hydrogels hold immense promise for biomedical applications, but conventional gelation processes often struggle to achieve the precision and complexity required for advanced functionalities such as soft robotics, targeted drug delivery, and tissue engineering. This study introduces a class of 3D-printable magnetic hydrogels with tunable stiffness, adhesion, and magnetic responsiveness, prepared through a simple and efficient "one-pot" method. This approach enables precise control over the hydrogel's mechanical properties, with an elastic modulus ranging from 43 kPa to 277 kPa, tensile strength from 93 kPa to 421 kPa, and toughness from 243 kJ/m3 to 1400 kJ/m3, achieved by modulating the concentrations of acrylamide (AM) and Fe3O4 nanoparticles. These hydrogels exhibit rapid heating under an alternating magnetic field, reaching 44.4 °C within 600 s at 15 wt%, demonstrating the potential for use in mild magnetic hyperthermia. Furthermore, the integration of Fe3O4 nanoparticles and nanoclay into the AM precursor optimizes the rheological properties and ensures high printability, enabling the fabrication of complex, high-fidelity structures through extrusion-based 3D printing. Compared to existing magnetic hydrogels, our 3D-printable platform uniquely combines adjustable mechanical properties, strong adhesion, and multifunctionality, offering enhanced capabilities for use in magnetic actuation and hyperthermia in biomedical applications. This advancement marks a significant step toward the scalable production of next-generation intelligent hydrogels for precision medicine and bioengineering.

Fast fabrication of stimuli-responsive MXene-based hydrogels for high-performance actuators with simultaneous actuation and self-sensing capability.

Poly(N-isopropylacrylamide) (PNIPAM) composite hydrogels have recently emerged as promising candidates for soft hydrogel actuators. However, developing a facile and fast method to obtain multifunctional PNIPAM hydrogel actuators with simulating biological versatility remains a major challenge. Herein, we developed a fast-redox initiation system to prepare PNIPAM/sodium carboxymethyl cellulose (CMC)/T3C2Tx MXene nanocomposite hydrogel with multidirectional actuating behaviors and improved mechanical properties. The rapid thermoresponsive behavior of the PNIPAM/CMC/MXene layer bestows its corresponding bilayer actuator with an extraordinary actuation speed of 9.36°/s in hot water. Owing to the high photothermal conversion of MXenes, this PNIPAM/CMC/MXene hydrogel displays a range of remote-controlled actuations upon NIR light irradiation, including bending, rolling, displacement, and simulations of the sea eel's hunting behaviors in a water environment. More importantly, based on the excellent electrical properties of MXene, the PNIPAM/CMC/MXene-based hydrogel actuators have accomplished a self-sensing function by integrating the surface temperature-bending angle-the relative resistance changes during the NIR light-driven actuation process. The photothermal actuator's integrated actuation and sensing capabilities have facilitated the feedback of the contact and movement dynamics of the bioinspired artificial tongue. The straightforward preparation and multifunctional design of MXene-based hydrogel may facilitate the development of soft smart actuators.

Fundamentals and Advances in Stimuli-Responsive Hydrogels and Their Applications: A Review.

This review summarizes the fundamental concepts, recent advancements, and emerging trends in the field of stimuli-responsive hydrogels. While numerous reviews exist on this topic, the field continues to evolve dynamically, and certain research directions are often overlooked. To address this, we classify stimuli-responsive hydrogels based on their response mechanisms and provide an in-depth discussion of key properties and mechanisms, including swelling kinetics, mechanical properties, and biocompatibility/biodegradability. We then explore hydrogel design, synthesis, and structural engineering, followed by an overview of applications that are relatively well established from a scientific perspective, including biomedical uses (biosensing, drug delivery, wound healing, and tissue engineering), environmental applications (heavy metal and phosphate removal from the environment and polluted water), and soft robotics and actuation. Additionally, we highlight emerging and unconventional applications such as local micro-thermometers and cell mechanotransduction. This review concludes with a discussion of current challenges and future prospects in the field, aiming to inspire further innovations and advancements in stimuli-responsive hydrogel research and applications to bring them closer to the societal needs.

Magnetically induced stress birefringence in stimuli-responsive hydrogels

We report the appearance of stress birefringence induced by an external magnetic field in stimuli-responsive hydrogels containing magnetic nanoparticles (Fe3O4).

Development of a pH-Responsive Antimicrobial and Potent Antioxidant Hydrogel for Accelerated Wound Healing: A Game Changer in Drug Delivery.

Stimuli-responsive hydrogels have the capability to alter their state in response to changes in physiological signals within their application environment, providing distinct benefits in drug delivery applications. Here, the acidic pH typically found in acutely infected wounds can be effectively managed by incorporating a pH-responsive Ag+ loaded system within the hydrogel, thereby ensuring efficient drug use and preventing potential toxicity from the sudden release of silver ions. The antimicrobial composite hydrogel HAMA/GelMA-CA/Ag+ provides some tissue adhesion and accelerates wound healing. GelMA-CA is synthesized by modifying gelatin methacryloyl (GelMA) with caffeic acid (CA), while hyaluronic acid methacryloyl (HAMA) is introduced to prepare a double network hydrogel. Silver nitrate is then introduced to make it pH-responsive through the formation of coordination between the polyphenolic structure of caffeic acid and the silver ions. The composite hydrogel exhibited excellent antioxidant properties and strong antimicrobial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, the composite hydrogel accelerated the promotion of wound healing in a rat model of S. aureus-infected wounds. In conclusion, the HAMA/GelMA-CA/Ag+ hydrogel is a promising bioactive material that can be used as a wound dressing to promote the healing of acutely infected wounds.

Polydopamine-modified MXene-integrated photothermal responsive hydrogel for constructing rapid photothermal and self-sensing gradient hydrogel actuators

Abstract PNIPAm-based stimuli-responsive hydrogel actuators have made significant progress. By introducing responsive modules such as photothermal nanoparticles, the hydrogel can respond to environmental changes and construct anisotropic structures, allowing the hydrogel actuators to quickly bend and realize complex shape deformation. How-ever, there remains a need to enhance the mechanical properties of these hydrogels to accommodate multiple deformation actions and different application scenarios, and enhance the compatibility between nanoparticles and the hydrogels to improve the comprehensive performance of materials are still issues that need to be solved. In this study, we modified two-dimensional MXene nanosheets with polydopamine (PDA) to obtain P-MXene, which served as a photothermal agent and can be stably dispersed within the hydrogel system. We copolymerized thermosensitive N-isopropylacrylamide (NIPAm) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) in situ and used a direct current (DC) electric field to induce a concentration gradient distribution of P-MXene nanosheets within the hydrogel, resulting in the preparation of anisotropic gradient hydrogel actuators with good stretchability and conductivity. The hydrogel structure was characterized using scanning electron microscopy (SEM) and the Fourier transform infrared (FTIR) spectra. The swelling properties, mechani-cal properties and conductivity of the hydrogel were studied. The actuation behavior of P(NIPAm-DMAEMA)/P-MXene gradient hydrogel actuators under different thickness and electric field intensity was investigated. Additionally, the sensitivity and stability of the conductive hydrogel actuators were tested. and the functions of monitoring human health and information transmission were realized. It integrated with rapid photo responsiveness and self-sensing capabilities to monitor the defor-mation process of the actuators through real-time relative resistance changes during the actuations. This work is expected to expand the application field of soft hydrogel actuators and provide new insights into the design of a new generation of soft robots.

Stimuli-responsive hydrogels for skin wound healing and regeneration

AbstractSkin wounds are not only an aesthetic concern but also pose great risks to quality of life and general health. As the most promising biomaterial, hydrogels are three-dimensional polymeric networks and have attracted intense research attention. Hydrogels have developed a diverse range of biomedical and biopharmaceutical applications, owing to their large water content, biocompatibility, tunable mechanical properties, and stimuli-responsiveness. Stimuli-responsive hydrogels are smart materials which exhibit gelation, structural, degradation, performance and function changes when treated with external stimulations. Using these hydrogels to prepare wound dressing is a rapidly growing research area and has exhibited encouraging healing outcomes in small animal models, especially for the treatment of chronic wounds, diabetic wounds, and persistent skin inflammations. The present work gives a detailed and critical analysis on the design strategies, gelation mechanisms, materials selection, stimuli-responsiveness, hydrogel degradation, drug release profiles, and treatment outcomes of wound dressings prepared by the hydrogels with sensitivity to temperature, pH, reactive oxygen species (ROS), glucose, enzymes, and lights. We summarize, analyze, and critically evaluate the most recent publications in this area to explain, compare, and assess why and how various synthetic and bio-polymers are utilized by materials scientists to develop the next generation of skin wound dressing and regeneration. Graphical abstract

Hydrogel-based Soft Robotics for Surgical Machinery

Hydrogel-based soft robotics represent a transformative approach in surgical machinery, offering unparalleled adaptability, biocompatibility, and precision for minimally invasive procedures. Hydrogels, with their high water content and tunable mechanical properties, mimic soft biological tissues, making them ideal for applications in delicate surgical environments. This research explores the integration of hydrogel materials into soft robotic systems, focusing on their fabrication, actuation mechanisms, and performance in surgical applications. Key advancements include the development of stimuli-responsive hydrogels that enable precise control of movement and force, enhancing the capability to navigate complex anatomical structures. The study also examines computational models for simulating hydrogel behavior and optimizing robotic designs. While the potential benefits of hydrogel-based soft robotics in improving patient outcomes are significant, challenges remain in ensuring durability, scalability, and reliable control systems. This research aims to address these limitations by integrating advanced materials science with robotic engineering. By doing so, it contributes to the evolution of surgical technologies, paving the way for safer and more effective procedures.

Numerical modeling of heterogeneous stimuli-responsive hydrogels.

In this paper, we introduce a computational technique for modeling heterogeneous thermoresponsive hydrogels. The model resolves local fluid-solid interactions in hydrogel pores during the deswelling process. The model is a Lagrangian particle-based technique, which benefits from computational grids that represent polymer beads inside hydrogel scaffolds. The results show that the mechanical properties of hydrogels during deswelling, e.g., shrinkage ratio and elastic modulus, have a direct effect on the development of the front of expelled fluid. It is also observed that in certain parameter regimes the hydrogel may generate inertial fluid jets at the early stages of deswelling. Finally, simple heterogeneous designs are developed using Menger sponge-inspired shapes to investigate the effect of design heterogeneity on promoting directional release.

Stimuli-responsive hydrogel microspheres encapsulated with tumor-cell-derived microparticles for malignant ascites treatment

Tumor-cell-derived microparticles (TMPs) have been recognized as chemotherapeutic drug carriers and immunomodulators for anti-tumor therapy. Research in the clinical application of TMPs has been devoted to developing an effective delivery formulation that could enhance their therapeutic effects. Here, we propose thermal-responsive agarose hydrogel microspheres (MTX-TMPs@MSs) with encapsulation of Methotrexate (MTX)-packaging TMPs (MTX-TMPs) and black phosphorus quantum dots (BPQDs) by microfluidic technology for synergistic treatment of malignant ascites. The laden MTX-TMPs, separated from apoptotic tumor cells, could target tumor cells for the delivery of chemotherapy drugs and modulate the tumor immune microenvironment. Under near-infrared (NIR) induced thermal stimulation, MTX-TMPs could be controllably released from the low-melting-point agarose matrix hydrogel microspheres for chemotherapy (CHT) and immunotherapy (IMT). In addition, benefiting from photothermal therapy (PTT)-induced tumor immunogenic death, the anti-tumor immune response triggered by MTX-TMPs was further enhanced. Based on these features, the MTX-TMPs@MSs could remarkably eliminate tumor cells in vitro and obviously suppress tumor growth in vivo through synergistic PTT, CHT, and IMT. Therefore, it is envisaged that this TMPs-integrated microcarrier will have promising applications in clinical tumor therapy. Statement of SignificancePrimary liver cancer ranks third among the causes of cancer deaths globally, with hepatocellular carcinoma (HCC) being the most common type. In particular, patients with advanced HCC accompanied by malignant ascites, a common complication, indicate tumor metastasis and a poor prognosis. In this paper, we developed stimuli-responsive hydrogel microspheres from microfluidics for the delivery of methotrexate (MTX)-loaded tumor-cell-derived microparticles (MTX-TMPs) for synergistic chemotherapy, photothermal therapy, and immunotherapy. The release of MTX-TMPs from hydrogel microspheres could be on-demand controlled through BPQDs-mediated photothermal stimulus. On the other hand, BPQDs-mediated mild hyperthermia cooperatesss with MTX-TMPs-induced chemotherapy could participate in remodeling the tumor immunosuppressive microenvironment. Thus, the prepared microcarrier system holds great promise for tumor therapy.

In-situ Forming Multipolymeric Glucose-Responsive Hydrogels.

Stimuli-responsive hydrogels (HGs) have shown promise for smart drug delivery applications. Specifically, glucose-responsive HGs having phenylboronic acid (PBA) functional groups are extensively pursued for insulin delivery in hyperglycemia. Current polymeric glucose-responsive HGs are cumbersome to fabricate and show a limited insulin release profile. Herein, we develop a straightforward fabrication of glucose-responsive multipolymer HGs (MPHGs) using a three-component in situ mixing. Molecular cargo, such as insulin, was loaded during the gelation. Heterobifunctional formylphenylboronic acid (FPBA) crosslinkers were used to interconnect polyvinyl alcohol (PVA) and branched polyethyleneimine (PEI) via boronate ester and imine bonds, respectively. Three positional isomers of FPBA (2FPBA, 3FPBA, and 4FPBA) resulted in HGs with distinct viscoelastic behaviors under the same conditions. HGs derived from 4FPBA exhibited more solid-like properties compared to 2FPBA and 3FPBA due to a higher crosslinking density. All the HGs exhibited glucose-responsive dissolution and release of embedded insulin cargo without disrupting the native structure. Insulin release profiles show a higher glucose-responsive release from 4FPBA-derived MPHGs. All the HGs were injectable, self-healing, and noncytotoxic below 10 μg/ml concentrations. The MPHGs developed in this study uncover new directions in creating glucose-responsive matrices for self-regulating drug delivery applications. In the future, detailed in vivo studies will be performed for clinical applications.

Stimuli-Responsive Vesicles and Hydrogels Formed by a Single-Tailed Dynamic Covalent Surfactant in Aqueous Solutions.

Controlling the hierarchical self-assembly of surfactants in aqueous solutions has drawn much attention due to their broad range of applications, from targeted drug release, preparation of smart material, to biocatalysis. However, the synthetic procedures for surfactants with stimuli-responsive hydrophobic chains are complicated, which restricts the development of surfactants. Herein, a novel single-tailed responsive surfactant, 1-methyl-3-(2-(4-((tetradecylimino) methyl) phenoxy) ethyl)-3-imidazolium bromides (C14PMimBr), was facilely fabricated in situ by simply mixing an aldehyde-functionalized imidazolium cation (3-(2-(4-formylphenoxy) ethyl)-1-methyl imidazolium bromide, BAMimBr) and aliphatic amine (tetradecylamine, TDA) through dynamic imine bonding. With increasing concentration, micelles, vesicles, and hydrogels were spontaneously formed by the hierarchical self-assembly of C14PMimBr in aqueous solutions without any additives. The morphologies of vesicles and hydrogels were characterized by cryogenic transmission electron microscopy and scanning electron microscopy. The mechanical properties and microstructure information of hydrogels were demonstrated by rheological measurement, X-ray diffraction, and density functional theory calculation. In addition, the vesicles could be disassembled and reassembled with the breakage and reformation of imine bonds by adding acid/bubbling CO2 and adding alkali. This work provides a simple method for constructing stimuli-responsive surfactant systems and shows great potential application in targeted drug release, drug delivery, and intelligent materials.

Kinetic and thermodynamic analysis of engineered alginate–chitosan hydrogel based scaffolds for drug delivery applications

The synthesis of stimulus–responsive hydrogel–based scaffolds has been extensively investigated for controlled drug delivery applications. This study focused on synthesizing alginate and chitosan–based scaffolds for potential use in releasing antibiotic antimycotic solution (AAS) drugs. The controlled release of AAS from AAS–loaded alginate–chitosan scaffolds was investigated under distinct temperatures viz. 37 °C, 25 °C, and 10 °C, labeled as scaffolds A, B, and C, respectively. Porosity assessment revealed consistent and substantial mean porosity percentage of 95.06 ± 2.01 % across all scaffolds. The lower temperature of 10 °C significantly contributed to a gradual and consistent cumulative release of 91.67 ± 1.47 %, compared to 37 °C (94.07 ± 1.89 %) and 25 °C (92.75 ± 1.51 %). The Korsmeyer–Peppas model exhibited high R2 values (0.98, 0.97 to 0.99) for scaffolds A, B, and C, indicating its suitability for describing the in–vitro release of AAS. Furthermore, the obtained release exponent values (0.60, 0.65, and 0.72 for scaffolds A, B, and C, respectively) suggest non–Fickian diffusion as the primary mechanism governing drug release. The release was also pH–dependent, with slower release at acidic (pH 3) and faster release under basic conditions (pH 8) due to varying swelling ratios. Evaluation of thermodynamic parameters viz. Ea, ΔG, ΔH and ΔS, using the rate constant of the Korsmeyer–Peppas model, revealed positive values of ΔH > 0 and ΔS > 0, indicating the prevalence of hydrophobic interactions in the release process.

Stimuli-responsive hydrogel actuators for skin therapeutics and beyond

Stimuli-responsive hydrogels are innovative soft materials that have garnered significant attention in recent years. These hydrogels can undergo phase transitions or structural changes in response to external stimuli, offering considerable potential for use as actuators. They can effectively be used for drug delivery and disease treatment by responding flexibly to a variety of stimuli. This paper first categorizes the types of external stimuli that hydrogel actuators respond to and outlines their applications in skin therapeutics. It then reviews therapeutic potentials of hydrogel actuators beyond the skin, and discusses the challenges and future prospects for the development of stimuli-responsive hydrogel actuators.

Advancements in Hydrogels for Corneal Healing and Tissue Engineering.

Hydrogels have garnered significant attention for their versatile applications across various fields, including biomedical engineering. This review delves into the fundamentals of hydrogels, exploring their definition, properties, and classification. Hydrogels, as three-dimensional networks of crosslinked polymers, possess tunable properties such as biocompatibility, mechanical strength, and hydrophilicity, making them ideal for medical applications. Uniquely, this article offers original insights into the application of hydrogels specifically for corneal tissue engineering, bridging a gap in current research. The review further examines the anatomical and functional complexities of the cornea, highlighting the challenges associated with corneal pathologies and the current reliance on donor corneas for transplantation. Considering the global shortage of donor corneas, this review discusses the potential of hydrogel-based materials in corneal tissue engineering. Emphasis is placed on the synthesis processes, including physical and chemical crosslinking, and the integration of bioactive molecules. Stimuli-responsive hydrogels, which react to environmental triggers, are identified as promising tools for drug delivery and tissue repair. Additionally, clinical applications of hydrogels in corneal pathologies are explored, showcasing their efficacy in various trials. Finally, the review addresses the challenges of regulatory approval and the need for further research to fully realize the potential of hydrogels in corneal tissue engineering, offering a promising outlook for future developments in this field.

Advances in Smart-Response Hydrogels for Skin Wound Repair

Hydrogels have emerged as promising candidates for biomedical applications, especially in the treatment of skin wounds, as a result of their unique structural properties, highly tunable physicochemical properties, and excellent biocompatibility. The integration of smart-response features into hydrogels allows for dynamic responses to different external or internal stimuli. Therefore, this paper reviews the design of different smart-responsive hydrogels for different microenvironments in the field of skin wound therapy. First, the unique microenvironments of three typical chronic difficult-to-heal wounds and the key mechanisms affecting wound healing therapeutic measures are outlined. Strategies for the construction of internal stimulus-responsive hydrogels (e.g., pH, ROS, enzymes, and glucose) and external stimulus-responsive hydrogels (e.g., temperature, light, electricity, and magnetic fields) are highlighted from the perspective of the wound microenvironment and the in vitro environment, and the constitutive relationships between material design, intelligent response, and wound healing are revealed. Finally, this paper discusses the severe challenges faced by smart-responsive hydrogels during skin wound repair and provides an outlook on the combination of smart-responsive hydrogels and artificial intelligence to give scientific direction for creating and using hydrogel dressings that respond to stimuli in the clinic.

Oligo-Adenine Derived Secondary Nucleic Acid Frameworks: From Structural Characteristics to Applications.

Oligo-adenine (polyA) is primarily known for its critical role in mRNA stability, translational status, and gene regulation. Beyond its biological functions, extensive research has unveiled the diverse applications of polyA. In response to environmental stimuli, single polyA strands undergo distinctive structural transitions into diverse secondary configurations, which are reversible upon the introduction of appropriate counter-triggers. In this review, we systematically summarize recent advances of noncanonical structures derived from polyA, including A-motif duplex, A-cyanuric acid triplex, A-coralyne-A duplex, and T ⋅ A-T triplex. The structural characteristics and mechanisms underlying these conformations under specific external stimuli are addressed, followed by examples of their applications in stimuli-responsive DNA hydrogels, supramolecular fibre assembly, molecular electronics and switches, biosensing and bioengineering, payloads encapsulation and release, and others. A detailed comparison of these polyA-derived noncanonical structures is provided, highlighting their distinctive features. Furthermore, by integrating their stimuli-responsiveness and conformational characteristics, advanced material development, such as pH-cascaded DNA hydrogels and supramolecular fibres exhibiting dynamic structural transitions adapting environmental cues, are introduced. An outlook for future developments is also discussed. These polyA derived, stimuli-responsive, noncanonical structures enrich the arsenal of DNA "toolbox", offering dynamic DNA frameworks for diverse future applications.

Advances in Chitosan-Based Smart Hydrogels for Colorectal Cancer Treatment

Despite advancements in early detection and treatment in developed countries, colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths worldwide. Conventional chemotherapy, a key option for CRC treatment, has several drawbacks, including poor selectivity and the development of multiple drug resistance, which often lead to severe side effects. In recent years, the use of polysaccharides as drug delivery systems (DDSs) to enhance drug efficacy has gained significant attention. Among these polysaccharides, chitosan (CS), a linear, mucoadhesive polymer, has shown promise in cancer treatment. This review summarizes current research on the potential applications of CS-based hydrogels as DDSs for CRC treatment, with a particular focus on smart hydrogels. These smart CS-based hydrogel systems are categorized into two main types: stimuli-responsive injectable hydrogels that undergo sol-gel transitions in situ, and single-, dual-, and multi-stimuli-responsive CS-based hydrogels capable of releasing drugs in response to various triggers. The review also discusses the structural characteristics of CS, the methods for preparing CS-based hydrogels, and recent scientific advances in smart CS-based hydrogels for CRC treatment.