Sol-gel Transition Research Articles

The Photocleavable Protein PhoCl-Based Dynamic Hydrogels.

Dynamic protein hydrogels have attracted increasing attention owing to their tunable physiochemical and mechanical properties, customized functionality, and biocompatibility. Among the different types of dynamic hydrogels, photoresponsive hydrogels are of particular interest. Here, we report the engineering of a photoresponsive protein hydrogel by using the photocleavable protein PhoCl. We employed the well-developed SpyTag and SpyCatcher chemistry to engineer PhoCl-containing covalently cross-linked hydrogels. In the hydrogel network, PhoCl, which can be cleaved into two fragments upon violet irradiation, is employed as a dynamic structural motif to regulate the cross-linking density of the hydrogel network. The resultant PhoCl-containing hydrogels showed photoresponsive viscoelastic properties. Upon violet irradiation, the PhoCl hydrogels soften, leading to an irreversible reduction in the storage moduli. However, no gel-sol transition was observed. Leveraging this light-induced stiffness change, we employed this hydrogel as a cell culture substrate to investigate the mechanobiological response of NIH-3T3 fibroblast cells. Our results showed that 3T3 cells can change their morphologies in response to the stiffness change of the PhoCl hydrogel substrate dynamically, rendering PhoCl-based hydrogels a useful substrate for other mechanobiological studies.

Fibrillar Hydrogel Inducing Cell Mechanotransduction for Tissue Engineering.

One of the key strategies for tissue engineering is to design multifunctional bioinks that balance printability with cytocompatibility. Here, we describe fibrillar hydrogels produced by Schiff base formation between B-type gelatin and oxidized sodium alginate, followed by the incorporation of type I collagen, yielding a new gel (MyoColl). The resulting hydrogel exhibits a temperature- and mass-ratio-dependent sol-gel transition, showing variability of hydrogel properties depending on the component ratio. MyoColl composition provides a convenient platform for biofabrication in terms of shear thinning, yielding, Young's modulus, and shape accuracy. Metabolic activity tests and fluorescent microscopy of 2D hydrogel-based mouse C2C12 myoblast cell culture show significant cytocompatibility of the developed carriers. In addition, primary signs of cell mechanotransduction and myofilament formation of 3D printed MyoColl-based cell cultures were detected and described. Due to these promising results, the described hydrogel composition has shown itself as a convenient platform for muscle tissue engineering.

One-pot fabrication of sodium deoxycholate based supramolecular self-healing antibacterial double network hydrogels

Double network (DN) hydrogels have emerged as a significant technology for enhancement of mechanical strength of weak supramolecular gels. In the present study, we report the one-pot route for design of a low molecular weight gelator based DN hydrogel wherein sodium deoxycholate (NaDC) forms the primary network entangled with agar matrix. Various compositions of the reported agar-NaDC hydrogels were examined through FTIR, sol-gel transition temperature (Tsg), XRD, circular dichroism (CD), scanning electron microscopy (SEM), hydrophobicity probe studies, Zeta potential studies and rheology measurements. Analysis of all studies together reveal that 1 mg/ml agar-NaDC DN hydrogel is the optimum composition that exhibits dense networking with primarily β-sheet like structure, highest mechanical strength as well as self-healing characteristics with reversed optical activity and highest Tsg. Antibacterial activity studied using inhibition zone method suggests that 1 mg/ml agar-NaDC gel demonstrates significant bactericidal effect unlike the pure gel with an inhibition zone of ∼25 mm against E.coli after 24 h and ∼32 mm after 48 h incubation. The antibacterial activity was unique for this composition of the DN hydrogel which is attributed to its reversal in optical activity exhibiting positive cotton effect resulting in stronger interaction with the bacterial cell wall. Additionally, nearly 2 times reduced water absorption capacity of the 1 mg/ml agar-NaDC DN hydrogel compared to pure NaDC hydrogel ensures the retention of its mechanical strength as well as other properties in high moisture containing environment. Hence, the 1 mg/ml agar-NaDC DN hydrogel holds appreciable potential as a novel strong supramolecular self-healing antibacterial hydrogel with sustained release characteristics primarily important for biomedical applications.

Myosin supramolecular self-assembly: The crucial precursor that manipulates the covalent aggregation, emulsification and rheological properties of myosin

The transformation of molecular conformation and self-assembly properties of myosin during the heating process at different ionic strengths (0.2 M, 0.4 M and 0.6 M NaCl) and its effect on rheological behavior and emulsification properties were investigated. Under incubation temperatures between 40 °C and 50 °C, myosin underwent a supramolecular self-assembly stage dominated by noncovalent forces (hydrogen bonding, ionic bonding and hydrophobic interactions). Higher ionic strength facilitated molecular rearrangement through enhanced swelling of myosin heads and head-to-head assemblies, which contributed to enhanced ordering and homogeneity of myosin covalent aggregates (above 60 °C) and manifested itself macroscopically as enhanced gel viscoelasticity and emulsion stability. In contrast, at lower ionic strength, the tail-to-tail assemblies of myosin led to the preferential formation of covalent cross-links in the tails, which resulted in the inability of molecular rearrangement and the formation of disordered aggregates and finally led to the deterioration of the gel and the destabilization of the emulsion. In conclusion, the supramolecular self-assembly behavior of myosin, as an intermediate process in myosin’s sol–gel transition, is crucial for the orderliness of myosin assemblies, gel network strengthening, and emulsion stability. The obtained insight provides a reference for the precise implementation of quality improvement strategies for meat products.

Synthesis and characterization of methacryl glycol chitosan as a novel functionally advanced thermogel for biomedical applications

Thermo-responsive hydrogels (thermogels), known for their sol-gel transition capabilities, have garnered significant interest for biomedical applications over recent decades. However, conventional thermogels are hindered by intrinsic physicochemical and functional limitations that impede their broader utility. This study introduces methacryl glycol chitosan (MGC) as a novel thermogel, offering enhanced functionality and addressing these limitations. MGCs, synthesized through N-methacrylation of glycol chitosan, exhibit tunable thermogelling and photo-crosslinking behaviors. The thermo-reversible sol-gel transition of MGCs occurs within a 21–54 °C range, adjustable by polymer concentration and methacryl substitution degree. Photo-crosslinking using UV light further enhances the mechanical properties of MGC thermogels, creating thermo-irreversible, chemically crosslinked hydrogels. MGCs show no cytotoxic effects and effectively support cell encapsulation. In vivo studies demonstrate stable crosslinking with minimal UV-induced skin damage. Due to their unique thermo-sensitivity, multi-functionality, and customizable properties, MGC thermogels are promising novel biomaterials for various biomedical applications, particularly injectable tissue engineering and cell encapsulation, thus overcoming the limitations of conventional thermogels.

Rheology study of the starch gelatinization to understand the hematite depression process

Gelatinization of starch by NaOH is an essential stage for this depressant preparation to enhance its water solubility through the reverse cationic flotation. No investigation has explored the rheology of the starch gelatinization to demonstrate the hematite depression completeness. To fill the gap, this study examined the influence of a wide range of SNMRs (3:1, 5:1, 7:1, 9:1) to explore the efficiency of the gelatinization process. The main aim was to highlight how starch gel preparation can influence hematite depression in cationic reverse flotation. The steady and dynamic shear rheological measurements plus optical micrographs were assessed for the starch gel gelatinization process for different SNMR conditions. Various experiment outcomes indicated that through the starch gelatinization by SNMR>6:1, the solubilization did not occur completely (due to the presence of some pristine granules) and the gels exhibited solid-like behavior, as evidenced by < 1, 94.3s, and 32.0 Pa.s. The incomplete release of AP macromolecules into the solution was the cause of the poor hematite depression efficiency. Pretreating starch by SNMR ≤ 5:1 indicated a full release of both AM and AP species to the solution since the gels showed fluid-like behavior with >1, 0.7s, and 2.4 Pa.s. However, the excessive alkalinity promoted a reduction in the hydrodynamic size of macromolecules. These findings explain the better efficiency of SNMR=5:1 to depress hematite compared to SNMR=3:1. In general, starch preparation with SNMR=6:1 marked the onset of the sol-gel transition, and the gels exhibited a balance between fluid-like behavior and solid-like behavior.

Ease-of-manufacture highly transparent thin polyvinyl alcohol aerogel

The earliest silicon-based aerogels attracted attention due to their nanoscale porous structure and high transparency. Still, they need to be more balanced with the poor mechanical properties. Their brittle structure limits the development of this promising new material. Therefore, the goal of this work is to optimize the mechanical properties of aerogels while maintaining transparency. The good mechanical properties of polymers have made them the material of choice for this work. Polyvinyl alcohol (PVA), which can undergo self-crosslinking through side-chain hydroxyl groups forming hydrogen bonds, was chosen as the raw material to simplify and expedite the production process. The production process was experimented with, analyzed, and refined. Considering the time efficiency of the experimental process, a one-step gelling method was invented to facilitate the sol-gel transition. The one-step gelling method maintained the high transparency of PVA aerogels and reduced the time required for the gelation process compared to the freeze-thawing method. This work employs carbon dioxide supercritical drying to ensure minimal structural collapse and maximize the porous structure’s retention. The transmittance of PVA aerogels can reach up to 93.67% at a wavelength of 1333 nm. The internal structure of aerogels with different PVA concentrations was observed using a Scanning electron microscope. Applying Beer-Lambert’s Law eliminated the effect of sample thickness on transparency. The relationship between the transparency of PVA aerogels, their microstructure, and macroscopic concentration was studied and analyzed for the first time. While ensuring light transmittance, the modulus of the PVA aerogel reached as high as 6.18 ± 0.56 MPa at 13 wt%.

Component Distribution, Shear-Flow Behavior, and Sol-Gel Transition in Mixed Dispersions of Casein Micelles and Serum Proteins.

The shear flow and solid-liquid transition of mixed milk protein dispersions with varying concentrations of casein micelles (CMs) and serum proteins (SPs) are integral to key dairy processing operations, including microfiltration, ultrafiltration, diafiltration, and concentration-evaporation. However, the rheological behavior of these dispersions has not been sufficiently studied. In the present work, dispersions of CMs and SPs with total protein weight fractions (ωPR) of 0.021-0.28 and SP to total protein weight ratios (RSP) of 0.066-0.214 and 1 were prepared by dispersing the respective protein isolates in the permeate from skim milk ultrafiltration and then further concentrated via osmotic compression. The partition of SPs between the CMs and the dispersion medium was assessed by measuring the dry matter content and viscosity of the dispersion medium after separating it from the CMs via ultracentrifugation. The rheological properties were studied at 20 °C via shear rheometry, and the sol-gel transition was characterized via oscillatory measurements. No absorption of SPs by CMs was observed in dispersions with ωPR = 0.083-0.126, regardless of the RSP. For dispersions of SPs with ωPR ≤ 0.21, as well as the dispersion medium of mixed dispersions with ωPR = 0.083-0.126, the high shear- rate-limiting viscosity was described using Lee's equation with an SP voluminosity (vSP) of 2.09 mL·g-1. For the mixed dispersions with a CM volume fraction of φCM ≤ 0.37, the relative high shear-rate-limiting viscosity was described using Lee's equation with a CM voluminosity (vCM) of 4.15 mL·g-1 and a vSP of 2.09 mL·g-1, regardless of the RSP. For the mixed dispersions with φCM > 0.55, the relative viscosity increased significantly with an increasing RSP (this was explained by an increase in repulsion between CMs). However, the sol-gel transition was independent of the RSP and was observed at φCM ≈ 0.65.

Lyotropic Liquid Crystalline Based Nasal Spray for Improved Parkinson's Treatment: Enhanced Superior Nasal Tract Deposition and Antioxidation Strategy

AbstractThe blood–brain barrier is one of the serious challenges in the treatment of Parkinson's disease (PD), which severely hinders the drug's brain bioavailability. In this study, a lyotropic liquid crystalline (LLC) based in situ gel nasal spray loaded with the first‐line drug Levodopa (LDA) for PD is developed to resolve this issue based on a nose‐to‐brain drug delivery approach. Specifically, the two key stages of LLC‐based in situ gel nasal spray, droplet deposition, and drug retention are tailored. By adjusting LLC's precursor solution's viscosity, the droplet deposition on the superior nasal tract can be increased by 18 times. Through nasal mucus‐triggered sol–gel transition, the LDA nasal cavity retention is prolonged by three times. The epigallocatechin gallate is incorporated into the LLC‐based in situ gel nasal spray to inhibit the autoxidation of LDA and alleviate the oxidative stress response in PD. The results show that the LLC‐based in situ gel nasal spray has a 26‐fold higher brain bioavailability of LDA compared to oral administration. The PD rats show a significant improvement in behavioral and cognitive disorders after administration. The LLC‐based in situ gel nasal spray is proved to work by reducing oxidative damage. This study is anticipated to offer a promising strategy for the clinical application of LDA.

Bifunctional Portable Powder for Freshwater Production With Moisture Harvesting and Undrinkable Water Purification.

Freshwater scarcity threatens human survival, particularly in extreme environments like deserts, oceans, and space. Compatible atmospheric water harvesting and undrinkable water purification offer an affordable approach to solving freshwater scarcity in these extreme environments. Nonetheless, developing composite sorbent to attain efficient atmospheric water harvesting and undrinkable water purification remains challenging. Hence, a portable hybrid hygroscopic powder (HLC powder) consisting of hydroxypropyl chitosan, dibenzaldehyde-functional poly(ethylene glycol), lithium chloride (LiCl), and nano carbon black is proposed. The HLC powder with optimized LiCl load can capture moisture from the air, showing a high water uptake of 1.76g g-1 at 34% relative humidity (RH) and appropriate over a wide humidity from 34% to 75% RH. pH-responsive sol-gel transition induced by Schiff base bonds transforms the HLC solution into hydrogel, inhibiting hydrated salt leakage. Meanwhile, to achieve efficient undrinkable water purification, the LiCl-free hybrid powder is utilized to convert the undrinkable water, including seawater, dye water, and human urine, to photothermal hydrogel evaporators with low evaporation enthalpies and high evaporation rates ranging from 1.81 to 2.05 kg m-2 h-1 under one sun. This strategy establishes a new path to conveniently obtaining freshwater, breaking hydrological restrictions.

Process Mapping of the Sol-Gel Transition in Acid-Initiated Sodium Silicate Solutions.

Fabricating large-scale porous bioactive glass bone scaffolds presents significant challenges. This study aims to develop formable, in situ setting scaffolds with a practical gelation time of about 10 min by mixing 45S5 bioactive glass with sodium silicate (waterglass) and an acid initiator. The effects of pH (2-11), waterglass concentration (15-50 wt.%), and acid initiator type (phosphoric or boric acid) were examined to optimize gelation kinetics and microstructure. A 10 min gelation time was achieved with boric acid and phosphoric acid at various pH levels by adjusting the waterglass concentration. Exponential and polynomial models were proposed to predict gelation times in basic and acidic environments, respectively. The optical properties of the gels were studied qualitatively and quantitatively, providing insights into gelation kinetics and structure. Acidic gels formed smaller particles in a dense network (pores < 550 nm) with higher light transmittance, while basic gels had larger aggregates (pores ~5 µm) and lower transmittance. As the waterglass concentration decreased, pore size and transmittance converged in both groups. The onset of gelation was detected around 8 min using the derivative of light transmittance. This work identifies the key factors controlling waterglass gelation and their impact on gel structure, enabling the tailored creation of formable, in situ setting bioactive glass bone scaffolds.

Development of Functionalized Polylactide Thin Films Using Poly(methylhydrogenosiloxane) Sol-Gel Process with Improved Antifouling Properties.

Biobased polylactide (PLA) films were modified with low reticulate polysiloxane gel acting as a scalable platform for the hydrophilization of polymeric film surface. The PLA thin film was first coated with poly(methylhydrogenosiloxane) (PMHS) by the sol-gel transition via the condensation of diethoxymethylsilane (DH) and triethoxysilane (TH) using trifluoromethanesulfonic acid as a catalyst. Then, hydrosilylation of Si-H bonds in the presence of Karstedt's catalyst allowed the covalent grafting of hydrophilic alkene-containing molecules, i.e., triethylene glycol monomethyl allyl (TEGMEA) and a new zwitterionic allylcarboxybetaine (ACB) synthesized for the first time by the quaternization of dimethyl allyl amine (DMAA) with β-propiolactone. PMHS coating on the PLA film was evidenced by Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The observation by atomic force microscopy (AFM) revealed a homogeneous coating with low roughness (RMS = 0.29 nm). The hydrophilicity of functionalized PLA films was determined by water contact angle (WCA) measurements using the captive bubble method. A large increase in wettability properties was observed for both grafting with TEGMEA (WCA = 38°) and ACB (WCA = 42°) in comparison with the native PLA film (WCA = 80°). Moreover, the biocompatibility and antifouling efficiency of functionalized PLA films were evaluated by protein adsorption, bacterial adhesion, and cytotoxicity tests. The results indicate that the grafting of the two types of hydrophilic compounds does not affect the biocompatibility of PLA while significantly reducing protein adsorption and bacterial adhesion, thus showing the great potential of this surface functionalization strategy for applications in the medical field.

Critical dynamics of the sol-gel transition studied using particle-tracking microrheology

Critical dynamics of the sol-gel transition studied using particle-tracking microrheology

ROS/Thermo dual-sensitive hydrogel loaded with a nanoemulsion of patchouli essential oil for ulcerative colitis

Patchouli essential oil (PEO) is acknowledged as a potent contender for the management of ulcerative colitis (UC). However, the limited ability of PEO to be absorbed by the body and its low stability substantially limit its potential uses. Furthermore, UC lesions are mainly concentrated in the rectal and colonic mucosa, with excessive production of reactive oxygen species (ROS). Herein, a nanoemulsion of PEO (PEONE) was developed to enhance the stability and bioavailability of a drug. Subsequently, we developed a novel platform for the rectal administration of a ROS/thermo dual-sensitive Bletilla striata polysaccharide-based hydrogel (RTH) co-loaded with PEONE to efficiently treat UC. As expected, the sol–gel transition of PEONE@RTH, after its intrarectal administration, resulted in its extended presence in the colon and facilitated its attachment to the inflammation site. Moreover, PEONE@RTH alleviated dextran sulfate sodium-induced UC symptoms by suppressing inflammation and oxidative stress, repairing the damage to the intestinal epithelial barrier (claudin-1 and occludin), increasing short-chain fatty acid content and inhibiting the MAPK signalling pathway. Additionally, PEONE@RTH exhibits exceptional safety and biocompatibility. Thus, PEONE@RTH has the potential to provide a novel approach for treating UC and other intestinal disorders characterised by similar clinical conditions.

Thermosensitive Hydrogels as Targeted and Controlled Drug Delivery Systems: Potential Applications in Transplantation.

Drug delivery in transplantation plays a vital role in promoting graft survival, preventing rejection, managing complications, and contributing to positive patient outcomes. Targeted and controlled drug delivery can minimize systemic effects. Thermosensitive hydrogels, due to their unique sol-gel transition properties triggered by thermo-stimuli, have attracted significant research interest as a potential drug delivery system in transplantation. This review describes the current status, characteristics, and recent applications of thermosensitive hydrogels for drug delivery. Studies aimed at improving allotransplantation outcomes using thermosensitive hydrogels are then elaborated on. Finally, the challenges and opportunities associated with their use are discussed. Understanding the progress of research will serve as a guide for future improvements in their application as a means of targeted and controlled drug delivery in translational therapeutic applications for transplantation.

Photo/thermo-sensitive chitosan and gelatin-based interpenetrating polymer network for mimicking muscle tissue extracellular matrix

The dynamic interplay between extracellular matrix (ECM), its 3D architecture and resident cells plays a pivotal role in cell behavior influencing essential processes like proliferation, migration, and differentiation. Matrix-based 3D culture systems have emerged as valuable tools to model organ and tissue interactions in vitro. A 3D matrix analog must possess high biocompatibility and fully reproduce the characteristics of the native tissue in terms of mechanical properties. In this regard, interpenetrating polymer networks (IPNs) are particularly attractive because of the high tunability of their physicochemical properties. In this study, a chitosan (Ch) and modified gelatin (GelMA) IPN with a sol-gel transition triggered by two external physical stimuli, UV light and temperature, was designed to mimic the muscle tissue ECM in terms of mechanical stiffness. The system was deeply characterized demonstrating to support not only the growth and viability of muscle cells embedded within the hydrogel, but also cell differentiation toward muscle phenotype.

Controlled Sol-Gel Transitions of Metal-Organic Membrane-Enveloped Cellulose Nanofibrils via Metal Coordination in Aqueous Media.

We report a metal coordination-driven sol-gel transition system where cellulose nanofibrils are enveloped by a rationally designed metal-organic membrane (MOM) in an aqueous medium. Specifically, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized bacterial cellulose (TOBC) is encapsulated within an MOM comprising Zn2+ and the chelator phytic acid (PA), denoted TOBCMOM. Using the DLVO theory, we elucidate how tuning the metal ion valence in TOBCMOM modulates the sol-gel transition by controlling interfibrillar attractive forces. Notably, TOBCMOM fluids exhibit relaxation times consistent with the Kohlrausch-Williams-Watts (KWW) function. Significantly, we demonstrate reversible, sustainable sol-gel transitions in TOBCMOM under stepwise mechanical strain. This facile approach enables rheological tailoring of aqueous media, promising for the development of advanced stimuli-responsive smart fluids for applications in cosmetics, food science, and pharmaceutical formulations.

Fabrication of Anatomically Equivalent Pectin-Based Multifilament Nerve Conduits.

Reuniting denuded nerve ends after a long segmental peripheral nerve defect is challenging due to delayed axonal regeneration and incomplete, nonspecific reinnervation, as conventional hollow nerve guides fail to ensure proper fascicular complementation and obstruct axonal guidance across the defects. This study focuses on fabricating multifilament conduits using a plant-derived anionic polysaccharide, pectin, where the abundant availability of carboxylate (COO-) functional groups in pectin facilitates instantaneous sol-gel transition upon interaction with divalent cations. Despite their advantages, pectin hydrogels encounter structural instability under physiological conditions. Hence, pectin is conjugated with light-sensitive methacrylate residues (49.8% methacrylation) to overcome these issues, enabling the fabrication of dual cross-linked multifilament nerve conduits through an ionic interaction-driven, template-free 3D wet writing process, followed by photo-cross-linking at 525 nm. The anatomical equivalence including peri-, epi-, and endoneurium structures of the customized multifilament conduits was confirmed through scanning electron micrographs and micro-CT analysis of rat and goat sciatic nerve tissues. Furthermore, the fabricated multifilament nerve conduits demonstrated cytocompatibility and promoted the expression of neuron-specific intermediate filament protein (NF-200) in PC12 cells and neurite outgrowth of 16.90 ± 1.82 μm on day 14. Micro-CT imaging of an anastomosed native goat sciatic nerve with an 8-filament conduit demonstrated precise fascicular complementation in an ex vivo interpositional goat model. This approach not only eliminates the need for a suture-intensive ligation process but also highlights the customizability of multifilament conduits to meet patient- and injury-specific needs.

Fabrication and characterization of novel curcumin-loaded thermoreversible high amylose maize starch emulsion gel

This study developed a novel thermoreversible emulsion gel system based on high amylose maize starch (HAMS) and investigated the impact of the oil-to-water ratio on its physicochemical properties and encapsulation performance (using curcumin as model guest molecule). Electron microscopy showed a tightly porous network structure of the HAMS-based emulsion gels. Thermal results revealed a sol-gel transition occurring in the range of 59.41 to 67.64 °C for the prepared emulsion gels. Rheological analysis suggested that all samples displayed shear-thinning behavior and HAMS-based emulsion gels exhibited typical gel-like behavior with the gel strength bolstered by higher aqueous phases. Particle size analysis showed that droplet size of emulsion gel decreased from 245 to 184 nm with increased starch aqueous phase content. Texture profile analysis indicated enhanced strength, hardness, and chewiness of the emulsion gel with increased aqueous phases. Curcumin encapsulation efficiency in the HAMS-based emulsion gel also improved with higher aqueous phase content, reaching up to 93.82 %, which attributed to the smaller droplets caused increased interfacial area. The novel HAMS-based emulsion gel system showed considerable encapsulation capacity and desirable mechanical properties. It provided valuable insights into the application of starch-based emulsion gels in food and medical area.

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.