Sol-gel Transition Research Articles

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.

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.

Operando Decoding Ion-Conductive Switch in Stimuli-Responsive Hydrogel by Nanodiamond-Based Quantum Sensing.

Thermal-responsive hydrogels are developed as ion-conductive switchs for energy storage devices, however, the molecule mechanism of switch on/off remains unclear. Here, poly(N-isopropylacrylamide-co-acrylamide) hydrogel is synthesized as a model material and nanodiamond (ND) based quantum sensing for phase change study is developed. First, micro-scale phase separation with cross-linked mesh structure after sol-gel transition is visualized in situ and water molecules are trapped by polymer chains and on a chemically "frozen" state. Then, the nano-scale inhomogeneous distributions of viscosity, thermal conductivity and ionic mobility in hydrogel at high temperature are observed by measuring the rotation, translation and zero-field splitting of NDs. Besides, the ionic mobility of hydrogel is found to be dependent not only on temperature but also on polymer concentration. These observations suggested that the physical "wall" induced by inhomogeneous phase separation at microscopic scale blocked the ion conduction pathways, providing a potential intrinsic explanation for ion migration shut-down of ionic hydrogels at high temperature.

Development of a natural ingredient based on phenolic compounds from propolis extract and bentonite and its application in carrageenan hydrogels

Nowadays, there is an increasing consumer demand for more natural and environmentally friendly food additives. The current research aimed to produce and characterize a new additive based on bentonite and the phenolic compounds from green propolis extract, as well as to characterize the effect of this additive on the rheological properties of carrageenan hydrogels. The new additive (biohybrid) was obtained after the adsorption of phenolic compounds on the clay platelets. The adsorption mechanism was explained by Langmuir and Freundlich models, which suggested that adsorbed phenolic compounds form a monolayer and multilayers on the clay surface. Despite phenolic adsorption, the physico-chemical attributes of the bentonite remained unchanged. The incorporation of the biohybrid (BH) increased the sol-gel transition temperature of carrageenan hydrogels. This research reports for the first time the development and application of a new natural ingredient with potential food applications.

Facile synthesis of hierarchically porous carbon monolith without templating agent for various applications in energy and catalysis

Monolithic carbon with hierarchically porous structure has a promising prospect for a wide range of applications in the fields of energy, environment, catalysis, etc. Due to the reliance on the utilization of templating agents, conventional preparation approaches often suffer from time-consuming preparation, complex post-processing, and uneconomical cost. Herein, we develop a novel strategy to match the sol-gel transition with the phase separation process for the direct preparation of hierarchically porous carbon monolith (HPCM) without templating agent. Resorcinol and resol are employed as carbon sources to adjust the polymerization for the formation of bi-continuous microstructure. Well-defined hierarchical pores and large specific surface area for fast mass diffusion enable the HPCM to be a prospective kind of electrode material in supercapacitor with an outstanding specific capacitance over 350 F g−1 (1.0 A g−1). After facile sulfonation, the modified HPCM can act as solid acid catalyst to realize a high-performance production of 5-hydroxymethylfurfural (5-HMF) in a 90 % yield with turnover frequency (TOF) value up to 155.9 h−1. Additionally, HPCM also exhibits an excellent Joule heating effect, which can be applied to the thermal management after compounding with phase change materials. The desirable integrated performance enables HPCM to be a valuable material suitable for various applications.

Near-Infrared Stimuli-Responsive Hydrogel Promotes Cell Migration for Accelerated Diabetic Wound Healing.

Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring an increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for the healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin-based composite hydrogel, N-isopropylacrylamide and polydopamine nanoparticles were incorporated to endow the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel, and the drug release rate could be controlled by NIR laser irradiation. NIR-triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of the composite hydrogel. The release of loaded LIN could effectively promote cell migration by activating EMT and enhancing angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound closure rate as compared with the pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can serve as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.

Ultralight M5 aerogels with superior thermal stability and inherent flame retardancy.

Ultra-lightweight materials often face the formidable challenge of balancing their low density, high porosity, high mechanical stiffness, high thermal and environmental stability, and low thermal conductivity. This study introduces an innovative method for synthesizing high-performance polymer aerogels to address the challenge. Specifically, we detail the production of poly (2,5-dihydroxy-1,4-phenylene pyridine diimidazole) (PIPD or M5) aerogels. This process involves chemically stripping M5 "super" fibers into nanofibers, undergoing a Sol-Gel transition, followed by freeze-drying and subsequent thermal annealing. The M5 aerogels excel beyond existing polymer aerogels, boasting an ultralight density of 6.03 mg cm-3, superior thermal insulation with thermal conductivity at 32 mW m-1 K-1, inherent flame retardancy (LOI = 50.3%), 80% compression resilience, a high specific surface area of 462.1 m2 g-1, and outstanding thermal stability up to 463 °C. These multi-faceted properties position the M5 aerogel as a front-runner in lightweight insulation materials, demonstrating the strategic use of high-performance polymer assembly units in aerogel design.

Research on preparation of micron-scale orthogonally aligned HMS patterns based on soft lithography

The soft lithography enables the fabrication of microfluidic honeycombs, which are micron-scale, orthogonally aligned hexagonal mesoporous silica (HMS) patterns with channels embedded within them, on silicon substrates. The process entails meticulous cleaning, precise master mold design (including features for channel alignment) using electron-beam lithography, generation of polydimethylsiloxane (PDMS) mold creation, ink formulation, and pattern transfer. Subsequent steps include the sol-gel transition, hardening, alignment verification, characterization, and optional functionalization. It is of the utmost importance to optimize these steps and the master design in order to achieve success. Therefore, the paper examines the creation of micron-scale HMS patterns with orthogonal alignment through the innovative application of soft lithography. The technique encompasses the strategic design of hexagonal motifs, precision master mold crafting, the PDMS stamps, and a meticulous sol-gel procedure, resulting in HMS structures that exhibit remarkable precision and adaptability. This paper underscores the transformative potential of soft lithography in the realm of advanced materials, which offers a controlled and uniform approach to size and uniformity. The refined soft lithography process not only achieves the precise orthogonal alignment of HMS patterns but also highlights its adaptability and economic viability in nanotechnology ventures.

Electrochemically assisted sol-gel deposition of bioactive gels for biomedical applications

AbstractSo far, the sol-gel process has been available to prepare precursor gels of bioactive glasses with various compositions. In this report, we described a novel coating method of bioactive gels on a titanium substrate where the sol-gel transition is controlled by applying external electric fields. The application of a constant current of 10 mA/cm2 in an acidic sol containing pre-hydrolyzed tetraethoxysilane, calcium nitrate, and ammonium dihydrogen phosphate led to the deposition of gels on the titanium cathodes due to the generation of OH– by water electrolysis as a catalyst of the sol-gel transition. The obtained gels, which were characterized to be amorphous and consisted of Si, Ca, and P, covered the titanium substrates as a coating. The bioactivity of the gels deposited was confirmed by soaking in a simulated body fluid (SBF) up to 7 days, suggesting that the electrochemically assisted sol-gel process is promising for providing bioactive coatings on metallic implants. Graphical Abstract