Search Results (75)

Thermosensitive hydrogels undergo reversible sol-gel phase transitions in response to changes in temperature. Owing to their excellent biocompatibility, mild reaction conditions, and controllable gelation properties, these hydrogels represent a promising class of biomaterials suitable for minimally invasive treatment systems in diverse biomedical applications. This review systematically summarizes the gelation mechanisms of thermosensitive hydrogels and optimization strategies to enhance their performance for broader application requirements. In particular, we highlight recent advances in injectable thermosensitive hydrogels as a carrier within stem cells, bioactive substances, and drug delivery for treating various tissue defects and diseases involving bone, cartilage, and other tissues. Furthermore, we propose challenges and directions for the future development of thermosensitive hydrogels. These insights provide new ideas for researchers to explore novel thermosensitive hydrogels for tissue repair and disease treatment. Full article

This study aimed to design dual-responsive chitosan–polylactic acid nanosystems (PLA@CS NPs) for controlled and targeted ledipasvir (LED) delivery to HepG2 liver cancer cells, thereby reducing the systemic toxicity and improving the therapeutic selectivity. Two formulations were developed utilizing ionotropic gelation and w/o/w emulsion techniques: LED@CS NPs with a size of 143 nm, a zeta potential of +43.5 mV, and a loading capacity of 44.1%, and LED-PLA@CS NPs measuring 394 nm, with a zeta potential of +33.3 mV and a loading capacity of 89.3%, with the latter demonstrating significant drug payload capacity. Since most drugs work through interaction with DNA, the in vitro affinity of DNA to LED and its encapsulated forms was assessed using stopped-flow and other approaches. They bind through multi-modal electrostatic and intercalative modes via two reversible processes: a fast complexation followed by a slow isomerization. The overall binding activation parameters for LED (cordination affinity, K_a = 128.4 M⁻¹, K_d = 7.8 × 10⁻³ M, ΔG = −12.02 kJ mol⁻¹), LED@CS NPs (K_a = 2131 M⁻¹, K_d = 0.47 × 10⁻³ M, ΔG = −18.98 kJ mol⁻¹) and LED-PLA@CS NPs (K_a = 22026 M⁻¹, K_d = 0.045 × 10⁻³ M, ΔG = −24.79 kJ mol⁻¹) were obtained with a reactivity ratio of 1/16/170 (LED/LED@CS NPs/LED-PLA@CS NPs). This indicates that encapsulation enhanced the interaction between the DNA and the LED-loaded nanoparticle systems, without changing the mechanism, and formed thermodynamically stable complexes. The drug release kinetics were assessed under tumor-mimetic conditions (pH 5.5, 10 mM GSH) and physiological settings (pH 7.4, 2 μM GSH). The LED@CS NPs and LED-PLA@CS NPs exhibited drug release rates of 88.0% and 73%, respectively, under dual stimuli over 50 h, exceeding the release rates observed under physiological conditions, which were 58% and 54%, thereby indicating that the LED@CS NPs and LED-PLA@CS NPs systems specifically target malignant tissue. Release regulated by Fickian diffusion facilitates tumor-specific payload delivery. Although encapsulation did not enhance the immediate cytotoxicity compared to free LED, as demonstrated by an in vitro cytotoxicity in HepG2 cancer cell lines, it significantly enhanced the therapeutic index (2.1-fold for LED-PLA@CS NPs) by protecting non-cancerous cells. Additionally, the nanoparticles demonstrated broad-spectrum antibacterial effects, suggesting efficacy in the prevention of chemotherapy-related infections. The dual-responsive LED-PLA@CS NPs allowed controlled tumor-targeted LED delivery with better selectivity and lower off-target toxicity, making LED-PLA@CS NPs interesting candidates for repurposing HCV treatments into safer cancer nanomedicines. Furthermore, this thorough analysis offers useful reference information for comprehending the interaction between drugs and DNA. Full article

Gelatin is a commonly used protein-based hydrogel. However, the thermo-reversible nature of gelatin makes it unstable at physiological and higher temperatures. Therefore, this study adopted phosphates and glutaminase transaminase (TG) to modify gelation and studied the effects of combining sodium hexametaphosphate (SHP) and TG on the structure and gel properties of TG-crosslinked gelatin. This study focused on the effects of different SHP concentrations (0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8 mmol/L) on the water distribution, textural properties, rheological properties, and microstructure of the TG-crosslinked gelatin gels. Results showed that the free water content in the TG-crosslinked gelatin gel declined with the increasing SHP addition when the concentration of SHP was kept below 2.0 mmol/L. The gel of TG-crosslinked gelatin at the SHP concentration of 1.6 mmol/L exhibited the highest hardness (304.258 g), chewiness (366.916 g) and η₅₀. All the TG-crosslinked gelatin gels with SHP modification were non-Newtonian pseudoplastic fluids. The G′ and G″ of TG-crosslinked gelatin increased before the SHP concentration reached 1.6 mmol/L, and the TG-crosslinked gelatin with 1.6 mmol/L SHP exhibited the largest G″ and G′. The fluorescence intensity of TG-crosslinked gelatin with SHP concentration above 1.6 mmol/L decreased with the increasing SHP concentration. SHP modified the secondary structure of TG-crosslinked gelatin gels. The gel of TG-crosslinked gelatin with the SHP concentration of 1.6 mmol/L exhibited a porous, smooth, and dense network structure. This research provides references for modifying gelatin and the application of gels in the encapsulation of bioactive ingredients and probiotics. Full article

Stimuli-responsive materials, particularly supramolecular hydrogels, exhibit a dynamic adaptability to external factors such as pH and ultrasound. Among these, phenylalanine (Phe)-derived hydrogels are promising due to their biocompatibility, biodegradability, and tunable properties, making them ideal for biomedical applications. This study explores the effects of pH and ultrasound on the gelation properties of N-substituted Phe derivatives, with a primary focus on the role of ultrasound in optimizing the gelation process. A series of N-substituted Phe derivatives were synthesized via reductive amination and hydrolysis. Hydrogel formation was possible with two of these compounds, namely G1 and G2, using the following two methods: heating–cooling (H–C) and heating–ultrasound–cooling (H–US–C). The critical gelation concentration (CGC), gelation kinetics, thermal stability (T_gel), and viscoelastic properties were assessed. Morphological and cytotoxicity analyses were performed to confirm the suitability of these gels for biomedical applications. Both G1 and G2 derivatives demonstrated enhanced gelation under the H–US–C protocol compared to H–C, with notable reductions in CGC (up to 47%) and gelation time (by over 90%). Ultrasound-induced gels led to an improved network density and stability, while maintaining thermal reversibility and mechanical properties comparable to those of hydrogels formed without ultrasound. Cytotoxicity studies confirmed a high biocompatibility, with cell viability rates above 95% across the tested concentrations. Given the similar rheological and morphological properties of the hydrogels regardless of the preparation method, drug release experiments were performed with representative gel samples and demonstrated the efficient encapsulation and controlled release of 5-fluorouracil and methotrexate from the hydrogels, supporting their potential as pH-responsive drug delivery platforms. This study highlights the role of ultrasound as a powerful tool for accelerating and optimizing the gelation process of supramolecular hydrogels, which is particularly relevant for applications requiring rapid gel formation. The developed Phe-based hydrogels also demonstrate promising characteristics as drug delivery systems. Full article

Hydrogels like agarose have long been used as sieving media for the electrophoresis-based analysis of biopolymers. During gelation, the individual agarose strands tend to form hydrogen-bond mediated double-helical structures, allowing thermal reversibility and adjustable pore sizes for molecular sieving applications. The addition of tetrahydroxyborate to the agarose matrix results in transitional chemical cross-linking, offering an additional pore size adjusting option. Separation of SDS-proteins during gel electrophoresis is an activated process defined by the interplay between viscosity, gelation/cross-link formation/distortion, and sample conformation. In this paper, the subunits of a therapeutic monoclonal antibody were separated by capillary SDS agarose gel electrophoresis at different temperatures. The viscosity of the separation matrix was also measured at all temperatures. In both instances, Arrhenius plots were used to obtain the activation energy values. It was counterintuitively found that larger SDS–protein complexes required lower activation energies while their low-molecular-weight counterparts needed higher activation energy for their electromigration through the sieving matrix. As a first approximation, we considered this phenomenon the result of the electric force-driven distortion of the millisecond range lifetime reticulations by the larger and consequently more heavily charged electromigrating molecules. In the meantime, the sieving properties of the gel were still maintained, i.e., they allowed for the size-based separation of the sample components, proving the existence of the reticulations. Information about the activation energy sheds light on the possible deformation of the sieving matrix and the solute molecules. In addition, the activation energy requirement study helped in optimizing the separation temperature, e.g., with our sample mixture, the highest resolution was obtained for the high-molecular-weight fragments, i.e., between the non-glycosylated heavy chain and heavy-chain subunits at 25 °C (lower E_a requirement), while 55 °C was optimal for the lower-molecular-weight light chain and non-glycosylated heavy chain pair (lower E_a requirement). Future research directions and possible applications are also proposed. Full article

We propose a new type of CNT hydrogel that has unique conductive and reversible characteristics. We found in previous studies that CNT dispersions became gelatinous without any gelators when a specific CNT was combined with a specific dispersant. This hydrogel has conductive properties derived mainly from the CNTs it contains; and even after gelation, it can be returned to a liquid state by ultrasonic irradiation. Furthermore, the liquid is gelable again. In this study, we prepared several types of CNTs and several types of dispersants, experimentally verified the possibility of gelation by combining them, and geometrically investigated the gelation mechanism to determine how this unique hydrogel is formed. As a result, we found that the experimental results and the theory examined in this study were consistent with the combination of materials that actually become hydrogels. We expect that this study will allow us to anticipate whether or not an unknown combination of CNTs and dispersants will also become gelatinous. Full article

Frequent removal and reapplication of wound dressings can cause mechanical disruption to the healing process and significant physical discomfort for patients. In response to this challenge, a dynamic covalent hydrogel has been developed to advance wound care strategies. This system comprises aldehyde functionalized chondroitin sulfate (CS-CHO) and thiolated hyaluronic acid (HA-SH), with the distinct ability to form in situ via thiol–aldehyde addition and dissolve on-demand via the thiol–hemithioacetal exchange reaction. Although rarely reported, the dynamic covalent reaction of thiol–aldehyde addition holds great promise for the preparation of dynamic hydrogels due to its rapid reaction kinetics and easy reversible dissociation. The thiol–aldehyde addition chemistry provides the hydrogel system with highly desirable characteristics of rapid gelation (within seconds), self-healing, and on-demand dissolution (within 30 min). The mechanical and dissolution properties of the hydrogel can be easily tuned by utilizing CS-CHO materials of different aldehyde functional group contents. The chemical structure, rheology, self-healing, swelling profile, degradation rate, and cell biocompatibility of the hydrogels are characterized. The hydrogel possesses excellent biocompatibility and proves to be significant in promoting cell proliferation in vitro when compared to a commercial hydrogel (HyStem^® Cell Culture Scaffold Kit). This study introduces the simple fabrication of a new dynamic hydrogel system that can serve as an ideal platform for biomedical applications, particularly in wound care treatments as an on-demand dissolvable wound dressing. Full article

The topic of this review is the physical gelling of liquid crystalline (LC) phases. It allows the combination of order and mobility of the LC-phase with macroscopic stability, which makes it a soft material. Thus, the gelled LCs acquire properties of LC-elastomers without the need for complicated chemistry to allow polymerization and crosslinking. But, instead, an LC-material (either a pure compound or a mixture) can be mixed with a few percent of a gel-forming agent, which self-assembles into long fibers that span the volume of the gel and make it a soft-solid. The use of azo-containing gel-forming agents thereby allows us to make gelation not only thermo-responsive, but also photo-responsive (trans-cis isomerization). This review discusses the micro-morphology of the gelled LCs and their influence on the mechanical properties and the switching in external electric fields. In addition, the potential of reversibility is discussed, which is not only interesting for recycling purposes, but also offers a route to inscribe a complex director pattern into the gelled liquid crystal. Full article

Chitosan is a deacetylated polymer of chitin that is extracted mainly from the exoskeleton of crustaceans and is the second-most abundant polymer in nature. Chitosan hydrogels are preferred for a variety of applications in bio-related fields due to their functional properties, such as antimicrobial activity and wound healing effects; however, the existing hydrogelation methods require toxic reagents and exhibit slow gelation times, which limit their application in biological fields. Therefore, a mild and rapid gelation method is necessary. We previously demonstrated that the visible light-induced gelation of chitosan obtained through phenol crosslinking (ChPh) is a rapid gelation method. To further advance this method (<10 s), we propose a dual-crosslinked chitosan hydrogel obtained by crosslinking phenol groups and crosslinking sodium tripolyphosphate (TPP) and the amino groups of chitosan. The chitosan hydrogel was prepared by immersing the ChPh hydrogel in a TPP solution after phenol crosslinking via exposure to visible light. The physicochemical properties of the dual-crosslinked hydrogels, including Young’s moduli and water retentions, were subsequently investigated. Young’s moduli of the dual-crosslinked hydrogels were 20 times higher than those of the hydrogels without TPP ion crosslinking. The stiffness could be manipulated by varying the immersion time, and the water retention properties of the ChPh hydrogel were improved by TPP crosslinking. Ion crosslinking could be reversed using an iron chloride solution. This method facilitates chitosan hydrogel use for various applications, particularly tissue engineering and drug delivery. Full article

Azobenzene photoswitches are fundamental components in contemporary approaches aimed at light-driven control of intelligent materials. Significant endeavors are directed towards enhancing the light-triggered reactivity of azobenzenes for such applications and obtaining water-soluble molecules able to act as crosslinkers in a hydrogel. Here, we report the rational design and the synthesis of azobenzene/alginate photoresponsive hydrogels endowed with fast reversible sol–gel transition. We started with the synthesis of three cationic azobenzenes (AZOs A, B, and C) and then incorporated them in sodium alginate (SA) to obtain photoresponsive supramolecular hydrogels (SMHGs). The photoresponsive properties of the azobenzenes were investigated by UV–Vis and ¹H NMR spectroscopy. Upon irradiation with 365 nm UV light, the azobenzenes demonstrated efficient trans-to-cis isomerization, with complete isomerization occurring within seconds. The return to the trans form took several hours, with AZO C exhibiting the fastest return, possibly due to higher trans isomer stability. In the photoresponsive SMHGs, the minimum gelation concentration (MGC) of azobenzenes was determined for different compositions, indicating that small amounts of azobenzenes could induce gel formation, particularly in 5 wt% SA. Upon exposure to 365 nm UV light, the SMHGs exhibited reversible gel–sol transitions, underscoring their photoresponsive nature. This research offers valuable insights into the synthesis and photoresponsive properties of cationic, water-soluble azobenzenes, as well as their potential application in the development of photoresponsive hydrogels. Full article

Aerogel fibers, characterized by their ultra-low density and ultra-low thermal conductivity, are an ideal candidate for personal thermal management as they hold the potential to effectively reduce the energy consumption of room heating and significantly contribute to energy conservation. However, most aerogel fibers have weak mechanical properties or require complex manufacturing processes. In this study, simple continuous silk fibroin–agarose composite aerogel fibers (SCAFs) were prepared by mixing agarose with silk fibroin through wet spinning and rapid gelation, followed by solvent replacement and supercritical carbon dioxide treatment. Among them, the rapid gelation of the SCAFs was achieved using agarose physical methods with heat-reversible gel properties, simplifying the preparation process. Hydrophobic silk fibroin–agarose composite aerogel fibers (HSCAFs) were prepared using a simple chemical vapor deposition (CVD) method. After CVD, the HSCAFs’ gel skeletons were uniformly coated with a silica layer containing methyl groups, endowing them with outstanding radial elasticity. Moreover, the HSCAFs exhibited low density (≤0.153 g/cm³), a large specific surface area (≥254.0 m²/g), high porosity (91.1–94.7%), and excellent hydrophobicity (a water contact angle of 136.8°). More importantly, they showed excellent thermal insulation performance in low-temperature (−60 °C) or high-temperature (140 °C) environments. The designed HSCAFs may provide a new approach for the preparation of high-performance aerogel fibers for personal thermal management. Full article

The aim of the study was to evaluate the effect of heat- (95 °C) and/or salt (0.1 M NaCl) treatment on the physical stability and rheological properties of oil-in-water emulsions stabilized with chickpea protein concentrates (CPCs) for various purposes. Thus, the particle size distribution (PSD), shear behavior, and long-term Turbiscan stability of the prepared emulsions were examined. The oscillatory (dynamic) measurements were also performed to obtain information on the viscoelasticity of tested fluids during thermal treatment. The obtained results indicated that the emulsion stabilized with gelling CPC (eC_g) was Newtonian fluid with a homogeneous structure, but susceptible to creaming. Heat-treated eC_g exhibited a sol–gel transition at 86 °C and formed fine-stranded aggregates without affecting stability. In turn, heat-induced gelation of eC_g in the presence of 0.1 M NaCl resulted in the formation of an aggregated, spatial gel network, stabilization of the system, and a significant change in both shear rheological properties and PSD. Contrariwise, emulsions stabilized with standard CPC (eC_s) were unstable heterogeneous systems containing both fine particles < 1 μm and coarse particles of about 100 μm, exhibiting shear-thinning and yield stress. The heat-induced viscoelasticity of eC_s was reversible, while heat- and salt-treated emulsions did not form a gel. Full article

Agarose forms a homogeneous thermoreversible gel in an aqueous solvent above a critical polymer concentration. Contrary to the prevailing consensus, recent confirmations indicate that agarose gels are also stable in non-solvents like acetone and ethanol. A previous study compared gel characterisations and behaviours in water and ethanol, discussing the gelation mechanism. In the current work, the ethanol gel is exchanged with water to explore the potential reversibility of the displacement of water in agarose. Initially, the structure is characterised using ¹H NMR in DMSO-d₆ and D₂O solvents. Subsequently, a very low yield (0.04) of methyl substitution per agarobiose unit is determined. The different gels after stabilisation are characterised using rheology, and their physical properties are compared based on the solvent used. The bound water molecules, acting as plasticizers in aqueous medium, are likely removed during the exchange process with ethanol, resulting in a stronger and more fragile gel. Next, the gel obtained after the second exchange from ethanol back to water is compared with the initial gel prepared in water. This is the first time where such gel has been characterised without undergoing a phase transition when switching from a good solvent to a non-solvent, and vice versa, thereby testing the reversibility of the solvent exchange. Reversibility of this behaviour is demonstrated through swelling and rheology experiments. This study extends the application of agarose in chromatography and electrophoresis. Full article

Currently, ultrashort oligopeptides consisting of fewer than eight amino acids represent a cutting-edge frontier in materials science, particularly in the realm of hydrogel formation. By employing solid-phase synthesis with the Fmoc/tBu approach, a novel pentapeptide, FEYNF-NH₂, was designed, inspired by a previously studied sequence chosen from hen egg-white lysozyme (FESNF-NH₂). Qualitative peptide analysis was based on reverse-phase high performance liquid chromatography (RP-HPLC), while further purification was accomplished using solid-phase extraction (SPE). Exact molecular ion confirmation was achieved by matrix-assisted laser desorption–ionization mass spectrometry (MALDI-ToF MS) using two different matrices (HCCA and DHB). Additionally, the molecular ion of interest was subjected to tandem mass spectrometry (MS/MS) employing collision-induced dissociation (CID) to confirm the synthesized peptide structure. A combination of research techniques, including Fourier-transform infrared spectroscopy (FTIR), fluorescence analysis, transmission electron microscopy, polarized light microscopy, and Congo red staining assay, were carefully employed to glean valuable insights into the self-assembly phenomena and gelation process of the modified FEYNF-NH₂ peptide. Furthermore, molecular docking simulations were conducted to deepen our understanding of the mechanisms underlying the pentapeptide’s supramolecular assembly formation and intermolecular interactions. Our study provides potential insights into amyloid research and proposes a novel peptide for advancements in materials science. In this regard, in silico studies were performed to explore the FEYNF peptide’s ability to form polyplexes. Full article

Reversible chemical covalency provides a path to materials that can degrade and recombine with appropriate stimuli and which can be used for tissue regeneration and repair. However, designing and preparing efficient and quickly self-healing materials has always been a challenge. The preparation strategies of photoresponsive gels attract a lot of attention due to their precise spatial and temporal control and their predetermined response to light stimulation. In this work, the linear copolymer PAC was synthesized via precipitation polymerization of acrylic acid and 7-(2-acrylate-ethoxylated)-4-methylcoumarin. The coumarin groups on the copolymer PAC side chains provide a reversible chemical cross-linking via photostimulation, which achieves reversible regulation of the gel network structure. The concentration of 18 wt% PAC solution produces gelation under irradiation with 365 nm. In contrast, PAC gel is restored to soluble copolymers under irradiation with 254 nm. Meanwhile, the mechanical and self-healing properties of the gel were also explored. It is demonstrated that the cracks of the gel can be repaired simply, quickly, and efficiently. Furthermore, the PAC copolymer shows an excellent adhesion property based on the reversible sol–gel transition. Thus, the PAC gel has considerable potential for applications in engineering and biomedical materials. Full article