Search Results (687)

The synthesis of enantiomerically pure chiral β-nitroalcohols is a crucial objective in asymmetric catalysis. In order to efficiently obtain such chiral products, we developed a series of thermoresponsive, oxazoline–copper catalysts (Cu^II-PN_xFe_yO_z) via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization. These catalysts can self-assemble in water into single-chain nanoparticles (SCNPs) with biomimetic behavior, in which intramolecular hydrophobic and metal-coordination interactions generate a confined hydrophobic cavity. Comprehensive characterization by FT-IR, TEM, DLS, CD, CA, and ICP analysis confirmed the nanostructure and composition. When applied to the aqueous-phase asymmetric Henry reaction between nitromethane and 4-nitrobenzaldehyde, the optimal catalyst (2.0 mol%) achieved a quantitative yield (96%) with excellent enantioselectivity (up to 99%) within 12 h. Furthermore, the thermosensitive poly(N-isopropylacrylamide, NIPAAm) block enabled facile catalyst recovery through temperature-induced precipitation above its lower critical solution temperature (LCST). This work presents an efficient and recyclable biomimetic catalytic system, offering a novel strategy for designing sustainable chiral catalysts for green organic synthesis. Full article

Thermosensitive nanogels undergo a volume phase transition in response to temperature changes, making them promising candidates for applications, such as water pollutant remediation and drug delivery. In this study, we investigated the thermosensitive volume phase transition of a neutral poly(N-isopropylacrylamide) (PNIPAM) nanogel using coarse-grained dissipative particle dynamics (DPD) simulations conducted using ESPResSo software with varying bead volumes. Langevin dynamics simulations were employed to compare the results. In DPD simulations, water is explicitly treated, whereas in Langevin dynamics, it is treated implicitly, and hydrophobic interactions are represented by an attractive potential between monomer beads. Our results, including the radius of gyration and various radial distribution functions, revealed a clear volume phase transition as the temperature varied, transitioning from an expanded state to a collapsed state. Notably, the volume phase transition observed in Langevin simulations is attributed to the attractive potential between the PNIPAM monomers, whereas in the DPD simulations, it arises from implicit hydrophobic interactions, obviating the need for an additional attractive potential between the monomer beads. This implicit hydrophobic effect originates from the temperature dependence of the Flory–Huggins interaction parameter. Full article

Background: Chitosan-based hydrogels exhibit excellent temperature-sensitive properties and are widely used as skin dressings. However, several challenges remain, such as long gelation times and difficulties releasing insoluble drugs, which limit their application in skin wound healing. In this study, we developed a novel sulfobutyl-β-cyclodextrin/quercetin@chitosan/hyaluronic acid hydrogel (Qe/SBE@CS/HA Gel). In this gel, SBE not only encapsulates Qe to form inclusion complexes, thereby enhancing the solubility of Qe, but also shortens the gelation time of thermosensitive gels through electrostatic adsorption with chitosan. Methods: Qe/SBE was prepared using the saturated solution method, while Qe/SBE@CS/HA gel was fabricated via electrostatic adsorption. The performance of the gels was evaluated using antibacterial, antioxidant, compatibility, and skin infection damage models. Results: The Qe/SBE@CS/HA Gel exhibits both thermosensitivity and acid sensitivity, releasing 91.9% of Qe in a medium with a pH of 5.0. This gel displays notable antibacterial activity and antioxidant characteristics. Furthermore, it shows excellent biocompatibility, as evidenced by hemolytic and in vivo degradation tests. The gel has the capacity to modulate chronic inflammation and facilitate angiogenesis and collagen synthesis, thereby significantly accelerating wound healing in wound and infection models. Conclusions: This multi-responsive and multifunctional gel shows potential as a therapeutic strategy for bacterial infection wounds. Full article

To address the susceptibility of traditional concrete to explosive spalling and the lack of in situ damage-monitoring methods at high temperatures, in this study, a novel self-sensing, high-temperature-resistant Engineered Cementitious Composite (ECC) was developed. The matrix contains eco-friendly glass sand reinforced with a hybrid system of polypropylene fibers (PPFs) and carbon fibers (CFs). The evolution of mechanical properties and the multimodal self-sensing characteristics of the ECC were systematically investigated following thermal treatment from 20 °C to 800 °C. The results indicate that the hybrid system exhibits a significant synergistic effect: through PFFs’ pore-forming mechanism, internal vapor pressure is effectively released to mitigate spalling, while CFs provide residual strength compensation. Mechanically, the compressive strength increased by 51.32% (0.9% CF + 1.0% PPF) at 400 °C compared to ambient temperature, attributed to high-temperature-activated secondary hydration. Regarding self-sensing, the composite containing 1.1% CF and 1.5% PPF displayed superior thermosensitivity during heating (resistivity reduction of 49.1%), indicating potential for early fire warnings. Notably, pressure sensitivity was enhanced after high-temperature exposure, with the 0.7% CF + 0.5% PPF group achieving a Fractional Change in Resistivity of 31.1% at 600 °C. Conversely, flexural sensitivity presented a “thermally induced attenuation effect” primarily attributed to high-temperature-induced interfacial weakening. This study confirms that the “pore-formation” mechanism, combined with the reconstruction of the conductive network, governs the material’s macroscopic properties, providing a theoretical basis for green, intelligent, and fire-safe infrastructure. Full article

Background: Diabetic wound healing is hampered by persistent inflammation and excessive neutrophil extracellular traps (NET) formation. Peptidylarginine deiminase 4 (PAD4) is a key enzyme driving this pathology. This study developed a thermosensitive chitosan/β-glycerophosphate hydrogel for the local delivery of a novel PAD4 inhibitor, YJ-2, to promote diabetic wound repair. Methods: A YJ-2-loaded hydrogel (CGY) was synthesized and characterized. In vitro studies used HaCaT cells and macrophages to assess proliferation, migration, NETs (via H3cit), and polarization. Efficacy was evaluated in diabetic C57 mouse wound models. Results: CGY exhibited temperature-sensitive gelation and sustained YJ-2 release. In vitro, YJ-2 inhibited NETs formation, reduced pro-inflammatory markers, promoted HaCaT migration, and induced M2 macrophage polarization. In vivo, CGY treatment significantly accelerated wound closure. Conclusions: Local hydrogel delivery of the PAD4 inhibitor YJ-2 effectively mitigates inflammation and NETs, promoting healing in diabetic wounds. This strategy represents a promising targeted therapy for diabetic wounds. Full article

Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide and a leading cause of cancer-related mortality. Current treatment options for advanced or unresectable HCC have limited efficacy and are often associated with systemic toxicity. In this study, a multifunctional, thermosensitive hydrogel-based delivery system was developed to enhance localized treatment of HCC. This system incorporates rhenium-188 sulfur colloid (¹⁸⁸Re-colloid), a β-emitting radiotherapeutic agent, and paclitaxel (PTX)-loaded micelles within a biodegradable PCL-PEG-PCL hydrogel matrix. The formulation enables in situ gelation at physiological temperatures, providing sustained release and prolonged retention of therapeutic agents at the tumor site. Physicochemical characterization confirmed the structural integrity and injectability of the formulations, while in vivo biodistribution studies in a murine hepatic tumor model demonstrated enhanced intratumoral accumulation and reduced systemic dispersion. The combined chemo-radiotherapeutic platform showed potential for improved therapeutic efficacy through synergistic action, offering a promising minimally invasive strategy for treating unresectable hepatocellular carcinoma. Full article

Insects can remotely detect human temperature, odor, and other stimuli as part of their host-seeking strategy. Such detection involves specific biomolecules, whose inhibition could limit host spotting and decrease the spread of insect-transmitted diseases. In this framework, invertebrate-specific ionotropic receptors (IRs) provide a potential molecular target to disable the insect’s capability to detect stimuli from prospective hosts. While several IRs have been studied in disease-transmitting insects, their inhibition remains unexplored. The rational design and development of such inhibitors requires the detailed characterization of the structure and functional mechanisms of IRs. Here, I discuss a possible, exploratory, and long-term approach for IR inhibition, which is based on research in mammalian thermosensitive transient receptor potential ion channels. Full article

Agomelatine (AG) is a novel antidepressant characterized by distinct mechanism of action and minimal side effects. However, extensive first-pass hepatic metabolism limits its clinical efficacy after oral administration, leading to low bioavailability (<5%). To get around these restrictions, the current study set out to create and assess a rectal thermosensitive in situ gel using biosynthesized AG-silver nanoparticles (AG-AgNPs). AG-AgNPs were successfully synthesized with gum acacia as a stabilizing agent, using silver nitrate as a precursor, and ascorbic acid as a reducing agent. The in situ gel formulation was optimized using a 3² factorial design, and then physicochemical, in vitro, and in vivo assessments were conducted. Nanoparticle formation was also evidenced by the appearance of a visible color change, UV-VIS, TEM, and XRD analysis techniques, which depicted spherical-shaped nanoparticles and a crystalline nature. The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine. Full article

Dynamic covalent hydrogels exhibiting multi-responsive and antibacterial properties offer significant potential for biomedical applications, including smart wound dressings and controlled drug delivery. Herein, a series of amphiphilic quaternized copolymers (Q-C8PEG-n) with tunable quaternization degrees was synthesized from C8PEG via iodomethane addition and characterized by ¹H NMR, COSY, FTIR, UV-vis spectroscopy, DLS, TEM, and zeta potential analyses, confirming successful quaternization and micelle formation. These copolymers displayed thermosensitive behavior, with cloud point temperatures increasing due to enhanced hydrophilicity. Q-C8PEG-3 micelles, incorporating diethanolamine units, were crosslinked with phenylboronic acid-grafted hyaluronic acid (HA-PBA) to yield dynamic covalent hydrogels (Gel) through reversible boronic ester bonds stabilized by B-N coordination. The Gel exhibited multi-responsiveness, undergoing degradation in acidic or alkaline conditions and exposure to glucose or H₂O₂. SEM confirmed a porous microstructure, enabling efficient drug encapsulation, as demonstrated by the release of Nile red (NR). In vitro antibacterial tests revealed enhanced post-quaternization efficacy, with the Gel showing strong activity against S. aureus. This micelle-crosslinked platform synergistically combines tunable stimuli-responsiveness with inherent antibacterial properties, holding promise for applications in wound healing and tissue engineering. Full article

Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising for advanced biomedical applications. This review critically surveys recent advances in the design, synthesis, and translational potential of thermo-responsive hydrogels, emphasizing nanoscale and hybrid architectures optimized for superior tunability and biological performance. Foundational systems remain dominated by poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp lower critical solution temperature near 32 °C, alongside Pluronic/Poloxamer triblock copolymers and thermosensitive cellulose derivatives. Contemporary developments increasingly exploit biohybrid and nanocomposite strategies that incorporate natural polymers such as chitosan, gelatin, or hyaluronic acid with synthetic thermo-responsive segments, yielding materials with markedly enhanced mechanical robustness, biocompatibility, and physiologically relevant transition behavior. Cross-linking methodologies—encompassing covalent chemical approaches, dynamic physical interactions, and radiation-induced polymerization are rigorously assessed for their effects on network topology, swelling/deswelling kinetics, pore structure, and degradation characteristics. Prominent applications include on-demand drug and gene delivery, injectable in situ gelling systems, three-dimensional matrices for cell encapsulation and organoid culture, tissue engineering scaffolds, self-healing wound dressings, and responsive biosensing platforms. The integration of multi-stimuli orthogonality, nanotechnology, and artificial intelligence-guided materials discovery is anticipated to deliver fully programmable, patient-specific hydrogels, establishing them as pivotal enabling technologies in precision and regenerative medicine. Full article

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation, and pain, for which conventional systemic therapies often lack sustained efficacy. Therefore, localized delivery platforms that provide both sustained release and therapeutic activity are urgently needed. We developed a thermosensitive injectable hydrogel—hydroxybutyl chitosan (HBC)—that transitions from a sol to a gel at physiological temperature (37 °C). Curcumin, a natural anti-inflammatory compound with poor bioavailability, was loaded to create a composite hydrogel system (Cur@HBC). HBC exhibited excellent injectability, stability, and biocompatibility. Cur@HBC enabled sustained release of curcumin and significantly attenuated OA progression in vivo, as evidenced by reduced cartilage degradation, decreased expression of MMP13 and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), improved Collagen II retention, and recovery of cartilage function. Mechanistically, curcumin inhibited chondrocyte apoptosis and promoted macrophage polarization toward the M2 phenotype. This study presents a dual-functional hydrogel platform that combines thermosensitive mechanical support with sustained anti-inflammatory drug delivery. The injectable Cur@HBC hydrogel shows great promise as a localized OA therapy, with the potential to improve joint function. Full article

Background/Objectives: Wound healing requires simultaneous pain control, inflammation management, infection prevention, and tissue regeneration. This study aimed to develop and evaluate in vitro a non-contact thermosensitive spray hydrogel combining lidocaine for rapid analgesia and allantoin for tissue repair. Methods: The effects of chitosan and Poloxamer 407 on viscosity, spray diameter, and bioadhesion ability of hydrogels were optimized using response surface methodology. Lead formulations (S1 and S2) were selected via a desirability function within the software. The pH, gelation temperature (T_G), rheological behavior, sprayability, bioadhesion, and lidocaine release using the dialysis bag method were assessed. The in vitro cytotoxicity, anti-inflammatory activity (TNF-α), and cell migration (scratch assay) of the formulations were investigated. Results: The viscosity values (42.7–58.7 mPa·s) indicated suitability for spraying at room temperature. T_G was 28.7 ± 0.6 °C (S1) and 29.3 ± 0.3 °C (S2), enabling rapid sol–gel transition at skin temperature. The lidocaine release reached 95–100% within 120 min. S2 exhibited lower viscosity and wider spray diameter, improving applicability on larger wound areas. In vitro cytotoxicity, scratch assay, and inflammatory marker analyses demonstrated that the optimized sprayable hydrogels exhibited a biocompatible and cell-healing profile. Conclusions: The developed thermosensitive spray hydrogel enables the combined delivery of lidocaine and allantoin, rapid gelation at body temperature, and touch-free administration. Its suitable viscosity and sprayability, and fast lidocaine release profile indicate high patient compliance and a significant advantage over conventional cream/ointment formulations, particularly regarding painless application, reduced contamination risk, enhanced therapeutic potential, and confirmed in vitro biocompatibility with supportive effects on keratinocyte behavior. Full article

Ultra-soft injectable hydrogels are paramount in biomedical applications such as tissue fillers, drug depots, and tissue regeneration scaffolds. Synthetic approaches relying on linear polymers are confronted by the necessity for significant dilution of polymer solutions to reduce chain entanglements. Bottlebrush polymers offer an alternative approach due to suppressed chain overlap and entanglements, which facilitates lower solution viscosities and increased gel softness. Leveraging the bottlebrush architecture in linear-bottlebrush-linear (LBL) block copolymer systems, where L is a thermosensitive linear poly(N-isopropylacrylamide) block, and B is a hydrophilic polyethylene glycol brush block, injectable hydrogels were designed to mimic tissues as soft as the extracellular matrix at high polymer concentrations. Compared to an analogous system with shorter brush side chains, increasing the side chain length enables a decrease in modulus by up to two orders of magnitude within 1–100 Pa at 20 wt% polymer concentrations, near to the physiological water content of ~70%. This system further exhibits thermal hysteresis, enabling stability with inherent body temperature fluctuations. The observed features are ascribed to kinetically hindered network formation by bulky macromolecules. Full article

Multimodal nanocomposites that combine optical and magnetic functionalities are of great interest for applications such as imaging and temperature sensing. Ternary CuInS₂ (CIS)-based quantum dots (QDs) offer low toxicity, strong near-infrared (NIR) emission, and high photostability, making them promising for optical nanothermometry and imaging. In this study, CIS QDs were synthesized using an aqueous cysteine-mediated approach. Manganese ferrite (MnFe₂O₄) nanoparticles were prepared as the magnetic component due to their non-toxicity and superparamagnetic properties. To integrate both functionalities, QDs and magnetic nanoparticles (MNPs) were encapsulated in silica and then combined to form multimodal CIS/MnFe₂O₄/SiO₂ nanocomposites. The structure and morphology of the materials were characterized by TEM and XRD, while their optical properties were examined using UV–Vis, photoluminescence (PL) spectroscopy. This design ensured optical isolation, preventing fluorescence quenching while maintaining colloidal stability. The obtained composites exhibited PL in the NIR region and a thermosensitivity of 2.04%/°C. TEM analysis confirmed uniform silica shell formation and successful integration of both components within the composite. The materials also retained the superparamagnetic behavior of MnFe₂O₄, making them suitable for combined optical and magnetic functionalities. These results demonstrate the potential of CIS/MnFe₂O₄/SiO₂ nanocomposites as multifunctional platforms for optical imaging, temperature monitoring, and magnetically modulated effects. Full article

Osteoporotic vertebrae are a uniquely challenging tissue for local delivery due to the complex geometry of cancellous bone, the proximity of the spinal cord, and the need for reliable site retention. These challenges can be met with the use of stimuli responsive, state transiting formulations by leveraging their unique capacity for minimally invasive implantation as a liquid, sol–gel transition in response to stimuli, and finally, release of a loaded therapeutic. Here, we present the formulation development of a thermosensitive methylcellulose–collagen hydrogel, functionalised with controlled release simvastatin, recently shown to enhance osteogenesis while also impeding osteoclast activity. We first optimised a formulation with collagen content of 0.4% w/v to achieve a thermosensitive system with sol–gel transition at 29 °C, shear-thinning/injectable properties, low cytotoxicity, and high biocompatibility. Incorporation of nano-hydroxyapatite for enhanced bone tissue mimicry revealed optimal performance at 100% w/collagen content, showing long-term hydrolytic stability, maintaining more than 100% of its mass after 28 days. A loading concentration of 1 mg of simvastatin to 1 g of hydrogel displayed sustained release of simvastatin over 35 days. Finally, the release of simvastatin from the hydrogel into in vitro conditions prevented the formation of osteoclasts but failed to boost osteogenesis. Together these findings reveal a series of desirable stimuli-responsive hydrogel properties, achieving minimally invasive application coupled with sustained release of a hydrophobic compound, which is potentially useful for spatially complex bone regeneration. Further this work demonstrates the challenge of dosing sustained release systems to achieve simultaneous osteogenesis and anti-osteoclastogenic effects. Full article