Mechanistic insights into gelation and rheological behavior of Pluronic F127-based thermoresponsive hydrogels

How Gellan gum gelation is affected by acyl substituents: from hierarchical organization to simple viscoelastic behavior.

Gellan gum, a linear anionic exopolysaccharide, is widely employed as a gelling agent owing to its biocompatibility and tunable rheological properties. Its degree of acylation determines high acyl (HA-Gg) and low acyl (LA-Gg) forms, yielding hydrogels with different chemical-physical properties. Rheological measurements show a distinct gelation mechanism: LA-Gg forms rigid, ionically crosslinked networks (G' ∼25 kPa; critical strain ≈2%) exhibiting two-step yielding, whereas HA-Gg produces softer elastic gels lacking hierarchical organization (G' ∼1 kPa; LVR extends up to ∼500% strain). Despite their wide use, the molecular mechanism by which acyl substituents affect Gellan gum gelation is still lacking. Here a comparison between HA-Gg and LA-Gg, combining spectroscopy, rheology, and atomistic molecular dynamics (MD) simulations within a single framework is performed, providing a molecular-level interpretation of these differences. In dilute regime, circular dichroism measurements reveals distinct behavior for LA-Gg and HA-Gg, in coil and double-helix conformations, respectively. MD simulations explain the observed features, showing that acylation enhances intra-helix hydrogen bonding, stabilizing the double-helix structure, while hindering calcium-mediated inter-helix associations. Overall, acylation exerts a dual effect: it strengthens local structural units, but weakening supramolecular connectivity. This interplay governs macroscopic mechanical response, enabling rational design of Gellan gum hydrogels with tailored properties.

An Injectable, Self-Healing Hydrogel Based on G-Quadruplexes/Phenylboronic Acid Composites with Antibacterial Activity

Injectable and self-healing hydrogels hold tremendous promise for biomedical applications; however, synchronously integrating robust mechanical adaptability, excellent cytocompatibility, and intrinsic antibacterial capabilities within a single matrix remains a significant challenge. In this study, we engineered an injectable, self-healing hydrogel based on dynamic cross-linking using guanosine-derived G-quadruplex supramolecular self-assembly and 3-aminophenylboronic acid (3-APBA)-mediated dynamic boronate ester. Systematic evaluation of various phenylboronic acid derivatives, GMP concentrations, K+ sources, and 3-APBA levels on gelation behavior yielded an optimized formulation. Scanning electron microscopy revealed that the optimized hydrogel exhibits a continuous, interconnected porous network structure after lyophilization. Thioflavin T fluorescence enhancement assays and circular dichroism spectroscopy further verify the formation of G-quadruplex-related ordered assemblies within the system. Rheological assessments demonstrate elasticity-dominated gel behavior, pronounced shear-thinning characteristics, and reversible structural breakdown and recovery under high and low strain cycles, indicating excellent injectability and self-healing properties. In vitro cytocompatibility evaluations show that the hydrogel possesses favorable cellular compatibility. Further antimicrobial studies reveal excellent in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli. In summary, the injectable, self-healing G-quadruplex hydrogel constructed in this study integrates a porous architecture, dynamic reversibility, and robust biological functionality, highlighting its promising potential in antibacterial applications.

Spontaneous Phase Separation Enables Rapid, Polymerization-Free Fabrication of Gels.

Hydrogels are cross-linked polymeric networks with wide applications in drug delivery, tissue engineering, biosensing, and environmental remediation. These hydrogels additionally host living cells, small molecules, and biological propagules, which further expand the applications of these materials. However, most, if not all, fabrication methods require covalent modifications. In this work, by deliberately selecting polymers with a known propensity to phase separate and formulating compositions far from the binodal boundary, we demonstrate the propensity of the system to transition directly into viscoelastic liquids or gels. This behavior is demonstrated using a model system of poly(ethylene glycol) (PEG) and dextran (DEX). We carried out rheological studies to provide insights into the viscoelastic behavior of these gels. We systematically characterized the gels through colorimetric assays, FTIR, MALDI-TOF, and thermogravimetric analysis (TGA) to discern the molecular compositions and solvent content of the gels. These experimental findings are supplemented with coarse-grained (CG) simulation insights to investigate the mechanistic origins of phase separation propensity with varying molecular weights of DEX. We utilized coexisting densities in the two phases using CG simulations to predict the role of DEX molecular weight in the partitioning of PEG and DEX in the two phases. Finally, we exploit the fabricated gel's ability to encapsulate live cells, antibiotics, and plant seeds. We anticipate that this ATPS-based fabrication technique will provide a scalable, cross-linker-free route to multifunctional gels, enabling advanced applications in drug delivery and responsive materials.

Structural reinforcement of Pluronic F127/chitosan thermoresponsive hydrogels through polydopamine incorporation for controllable drug transport.

Thermoresponsive Pluronic-based hydrogels are promising injectable drug delivery platforms but are often limited by weak mechanical integrity and control over drug transport. In this study, we report a polydopamine (PDA)-reinforced Pluronic F127/chitosan composite hydrogel, PCP-DOX, designed to strengthen network integrity and enable near-infrared (NIR)-responsive release without chemical crosslinkers. We have characterized the composite hydrogel for microstructure, rheology, and release kinetics, with photothermal performance and in vitro therapeutic efficacy evaluated under 808 nm NIR irradiation. We found a progressive network densification observed by electron microscopy together with a threefold increase in elastic modulus from approximately 11 kPa to 29 kPa. PCP-DOX exhibited a DOX entrapment efficiency of 98.24 ± 0.20%, indicating effective drug retention. Cumulative doxorubicin (DOX) release at 72 h decreased from 85.5% to 73.3% in the composite relative to the Pluronic-only system. Korsmeyer-Peppas modeling provided the best fit for the release kinetics, suggesting Fickian diffusion-governed transport, with the diffusion exponent increasing from 0.2975 to 0.4531 in the composite system, indicating enhanced diffusional resistance within the network. NIR irradiation at 1.0 W/cm2 enabled transient photothermal modulation of the composite network, producing stepwise release enhancement across repeated irradiation cycles. In vitro studies confirmed cytocompatibility of the blank hydrogel carrier, and combined NIR and DOX treatment yielded greater cytotoxicity than either modality alone, where the predominant cell death mechanism was determined to be apoptosis. These results establish PDA-mediated non-covalent reinforcement as an effective crosslinker-free strategy for engineering thermoresponsive hydrogels with tunable network mechanics and controllable NIR-responsive drug transport for localized chemo-photothermal therapy.

Tunable Sol-Gel Transition in Poloxamer Blends for Injectable Osteoarticular Applications.

Thermoresponsive poloxamers are commonly used in biomedical applications; however, their wider translational applicability depends on precisely controlling sol-gel transition behavior near body temperature while ensuring injectability and a favorable biocompatibility profile. In this study, blends of three clinically relevant poloxamers were evaluated to find formulations suitable for potential injectable meniscal and joint therapies. The rheological properties and temperature-dependent gelation of these formulations were characterized, followed by testing their injectability into meniscal defects and assessing biological responses in vitro. The gelation temperatures reported in this work were operationally defined from viscosity-based temperature sweep measurements. Biocompatibility, cell viability, and migration of outer fibrochondrocytes exposed to selected poloxamer hydrogels were examined to gauge their potential for orthopedic applications. Different material behaviors emerged based on polymer composition. Synperonic F-108 combined with Poloxamer 188 showed decreased adhesiveness and aggregation, along with maintained cell viability after prolonged incubation, indicating potential as a coating material or a general structural matrix. Conversely, blends of Kolliphor K 407 with Poloxamer 188 displayed temperature-dependent increases in viscosity. They formed stable gels at body temperature, maintaining a favorable biological response in direct-contact conditions, which supports their further evaluation in long-term injectable applications with controlled structural stability. These results show that careful selection and optimization of poloxamer blends allow tailoring material properties for specific biomedical functions. The adjustable thermoresponsive behavior, chemical inertness, and simple preparation of these triblock copolymers make them practical for further development in injectable biomaterials and drug delivery systems for osteoarticular repair.

Self-Degradable Temporary Plugging Agent Based on Dynamic Covalent Bond-Crosslinked Double-Network Hydrogels