Thermal-responsive Hydrogel Research Articles

In situ Thermal-Responsive Magnetic Hydrogel for Multidisciplinary Therapy of Hepatocellular Carcinoma.

Current surgical single modality treatments for hepatocellular carcinoma (HCC) were restricted by recurrence, blood loss, significant trauma, and poor prognostic. Although multidisciplinary strategies for HCC treatment have been highly recommended by the clinical guidelines, there was limited choice of materials and treatments. Herein, we reported an in situ formed magnetic hydrogel with promising bioapplicable thermal-responsiveness, strong adhesion in wet conditions, high magnetic hyperthermia, and biocompatibility, leading to efficient HCC multidisciplinary treatment including postoperative treatment and transarterial embolization therapy. In vivo results indicated that this hydrogel could reduce the postoperative recurrence rate. The hemostatic ability of the thermal-responsive hydrogel was further demonstrated in both the liver scratch model and liver tumor resection. Computed tomography imaging suggested that the hydrogel could completely embolize the arterial vessels of rabbit liver tumor by vascular intervention operation, which could serve as multidisciplinary responsive materials to external magnetic field and body temperature for HCC treatment.

Hydrogel Loaded with VEGF/TFEB-Engineered Extracellular Vesicles for Rescuing Critical Limb Ischemia by a Dual-Pathway Activation Strategy.

Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease, which causes many amputations and deaths. Conventional treatment strategies for CLI (e.g., stent implantation and vascular surgery) bring surgical risk, which are not suitable for each patient. Extracellular vesicles (EVs) can be a potential solution for CLI. Herein, vascular endothelial growth factor (VEGF; i.e., a crucial molecule related to angiogenesis) and transcription factor EB (TFEB; i.e., a pivotal regulator of autophagy) are chosen as the target gene to improve the bioactivity of EVs derived from endothelial cells. The VEGF/TFEB-engineered EVs (Engineered-EVs) are fabricated by genetically engineering the parent cells, and their versatile functions are confirmed using three cell models (human umbilical vein endothelial cells, myoblast, and monocytes). Injectable thermal-responsive hydrogel are then combined with Engineered-EVs to combat CLI. These results reveal that the hydrogel can enhance the stability of Engineered-EVs in vivo and release EVs at different temperatures. Moreover, the results of animal studies indicate that Engineered-EV/Hydrogel can significantly improve neovascularization, attenuate muscle injury, and recover limb function after CLI. Finally, mechanistic studies shed light on the therapeutic effect of Engineered-EV/Hydrogel due to the activated VEGF/VEGFR pathway and autophagy-lysosomal pathway.

Gecko’s Feet-Inspired Self-Peeling Switchable Dry/Wet Adhesive

Dynamic switchable attachment/detachment behavior can be extensively observed in biological systems. Although wide interest has been focused on the fabrication of biomimetic synthetic switchable adhesives, designing intelligent adhesive material systems under both dry and wet conditions by following a peeling mechanism from mechanical deformation-induced adaptive evolution of the interface geometric contact state is still challenging. Herein, inspired by the rolling behavior of gecko’s feet, one kind of novel multilayered self-peeling switchable dry/wet adhesive (SPSA) is developed by integrating thermal-responsive hydrogel layers, gecko’s feet-inspired mushroom-structured arrays, and mussel-inspired copolymer adhesive coatings together. The SPSA shows thermal-responsive curving behavior along with switchable dry and underwater adhesion. Theoretical analysis is performed for explaining the dynamic curvature-induced switchable peeling mechanism. By integrating Fe3O4 nanoparticles into the SPSA, remote control over switchable adhesion can be achieved by applying near-infrared laser radiation. Considering potential applications, the SPSA can be used for successfully bonding/separating and capturing/releasing objects in air and in underwater environments. This research provides a new route for developing intelligent adhesion systems and mobile devices/robots.

Preparation and Drug Release Properties of a Thermo Sensitive GA Hydrogel.

A high-strength galactomannan (GA)-based hydrogel with thermal response and pH response is introduced in this paper. GA, N-isopropylacrylamide (NIPAM), N-[3-dimethylamino)propyl]methylacrylamide (DMAPMA), and montmorillonite were used to form hydrogels through a simple mixed static system. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the structure and properties of the hydrogels. The compressive strength of the the hydrogel increased from 23.9 to 105.61 kPa with the increase of GA dosage from 0 to 1.5 wt%. When the NIPAM content in the monomer increased from 75% to 95%, the lower critical solution temperature (LCST) of the hydrogel changed from 36.5 to 45.8 °C. When the monomer content was higher than 10wt%, the swelling kinetics of the sample changed from the second-order equation to the first-order equation. With the increase of the proportion of NIPAM monomer, the release rate of bovine serum album in the early stage was faster, and the cumulative release rate was close to 100%.The release rate of bovine serum albumin at 37 °C was higher than that at 25 °C. The release rate of the hydrogel containing bovine serum albumin was the fastest under the condition of pH 7.4, followed by those at pH 6.6 and pH 5.0. The results showed that this thermal-responsive hydrogel has potential applications as a drug carrier for colon delivery.

A Sustainable and Efficient Artificial Microgel System: Toward Creating a Configurable Synthetic Cell

Artificial cells are a powerful platform in the study of synthetic biology and other valuable fields. They share a great potential in defining and utilizing the superiority of the living system. Here, a protein synthesis system based on thermal responsive hydrogels with porous structure is reported. The hydrogels can immobilize plasmids on the surface inside their porous structure through a volume phase transition upon 34 °C, forming an aggregation state of DNAs as in nature conditions. The artificial microgels can carry out bioreactions in cell-free systems and exhibit a sustainable and efficient performance for protein translation. The protein synthesis level reaches a maximum of twice more than that in a conventional solution system when the plasmid concentration is 10-20ng µL-1 , along with a doubled effective interval. This is perhaps attributed to confined transcription and translation processes in the near-surface area of hydrogels. Summarily, the research provides an easy-handling approach in fabricating effective microgels for cell-free synthesis and also inspirations for constructing a configurable artificial cell.

Construction of ionic thermo-responsive PNIPAM/γ-PGA/PEG hydrogel as a draw agent for enhanced forward-osmosis desalination

To achieve efficient forward osmosis (FO) for desalination, thermal-responsive hydrogels were synthesized by polymerization of N-isopropylacrylamide (NIPAM) in the presence of ionic polyglutamic acid (γ-PGA) and pore-forming polyethylene glycol (PEG). The equilibrium swelling ratio (ESR) and deswelling behaviour of PNIPAM/γ-PGA/PEG hydrogels were investigated at a series of dosages of reactants (γ-PGA, PEG, initiator and cross-linker). The PNIPAM/γ-PGA/PEG hydrogel revealed effective deswelling response at low temperature (35.20 °C). The highest ESR was 94.76 g/g, and the fastest dewatering ratio could reach 97.64% within 30 min. The optimal mass ratio of comonomers (NIPAM, γ-PGA and PEG), crosslinker and initiator was fixed at 1:0.2:1:0.01:0.01 determined by the response surface method (RSM). It was also found by RSM that the ESR was significantly dependent on cross-linker and the interaction between initiator and γ-PGA. The optimal hydrogel was examined as draw agent, employing deionized (DI) water and 0.05, 0.1 and 0.2 wt% NaCl solution as the feed, which showed the enhanced water fluxes at 1.99, 1.65, 1.31 and 1.08 LMH in initial 0.5 h. In addition, the hydrogel showed promising recyclability in term of water flux in three cycles.

Absorbent-Adsorbates: Large Amphiphilic Janus Microgels as Droplet Stabilizers.

Microgel particles are cross-linked polymer networks that absorb certain liquids causing network expansion. The type of swelling fluid and extent of volume change depends on the polymer-liquid interaction and the network's cross-link density. These colloidal gels can be used to stabilize emulsion drops by adsorbing to the interface of two immiscible fluids. However, to enhance the adsorption abilities of these predominantly hydrophilic gel particles, some degree of hydrophobicity is needed. An amphiphilic Janus microgel with spatially distinct lipophilic and hydrophilic sides is desired. Here, we report the fabrication of poly(ethylene glycol) diacrylate/poly(propylene glycol) diacrylate Janus microgels (JM) using microfluidic drop making. The flow streams of the two separate and immiscible monomer solutions are brought into contact and intersected by a third immiscible fluid in a flow-focusing junction to form Janus droplets. The individual droplets are cross-linked via UV irradiation to form monodispersed microgel particles with opposing hydrophilic and hydrophobic 3D-networked polymer matrices. By combining two chemically different polymer gel networks, an amphiphilic emulsion stabilizer is formed that adsorbs to the oil-water interface while its faces absorb their respective water or hydrocarbon solvents. The resulting water-in-oil emulsions are stabilized and destabilized via a thermal-responsive hydrogel. Stimuli-responsive droplets are demonstrated by adding a short-chain oligo ethylene glycol acrylate molecule to the hydrogel formulation on the Janus microgel particle. Droplets stabilized by these particles experience a sudden increase in droplet diameter around 60 °C. This work with absorbent particles may prove useful for applications in bio catalysis, fuel production, and oil transportation.

Bone marrow mesenchymal stem cells encapsulated thermal-responsive hydrogel network bridges combined photo-plasmonic nanoparticulate system for the treatment of urinary bladder dysfunction after spinal cord injury

Spinal cord injury (SCI) is a distressing injury and an irretrievable dramatic event that can debilitate victims for lifespan. Recovery and treatment of SCI is critical challenges for medicine, to overcome the hurdles stem cells and hydrogel scaffolds implantation is a boon for SCI recovery. In this regard, we reported the synthesis of Gold nanoparticles (Au NPs) loaded Agarose/Poly (N-isopropylacrylamide) (PNIPAM) as promising materials for SCI treatment. Herein, Au NPs was synthesized by well-established citrate reduction method and the prepared materials were characterised by UV–visible spectroscopy (UV–vis), Transmission electron microscopy (TEM), Fourier- transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and EDAX analysis. The microscopic images showed an elliptical or ovoid porous structure nature of hydrogel, and successful and homogenous loading of photo plasmonic nanoparticles into the hydrogel structure. The in vitro cell viability and inflammation analyses data exhibited that prepared hydrogels have no toxic to the cells and displayed high anti-regenerative ability with bone marrow Mesenchymal stem cells (MSCs) and macrophages cells. The in vivo analysis study demonstrated that the treated materials with encapsulated MSCs have greater nerve tissue regeneration efficacy which was confirmed by the results of BBB scores. The hind limb locomotion of treated model animals was totally vanished after post-operational surgery. It's established that implanted nano-hydrogel materials combined with MSCs have quicker recovery of motor function after post-operative surgery, when compared to the other implanted animal groups.

Response behaviors and mechanical strength of thermal responsive hydrogels fabricated by electrospinning

A UV-initiated crosslinking agent was incorporated in a poly(N-isopropylacrylamide) (PNIPAM)-based copolymer. Thermally-responsive hydrogels were then fabricated by the electrospinning of a PNIPAM-based copolymer and subsequently crosslinked under UV-treatment. The morphology of the fibrous structure was well maintained after many temperature induced swelling and de-swelling cycles. Both considerable degree of swelling and de-swelling ratios, along with an excellent response rate, were achieved with temperature variation. The influence of the crosslinker incorporated in the copolymer was investigated in terms of swelling/de-swelling ratios and rate, as well as the compressive strength and viscoelasticity of the hydrogels. Incorporation of crosslinker led to a 15% increase in copolymer molecular weight and 2 °C decrease of the volume phase transition temperature (VPTT). The diameters of fully swollen and shrunk electrospun fibers were around 10 times and 3 times those of as-spun fibers, respectively. Also, compared to as-spun fiber membrane, 4 times swelling in thickness and an unusual 0.6 time shrinking in the length and width are reported and explained for the first time. In terms of response time, both swelling and de-swelling equilibrium were reached within 10 min for samples with 0.7 mm thickness; negligible impact on the response rate was observed when the crosslinker to monomer ratio increased from 100:1 to 100:5. However, the increase of crosslinker ratio showed significant negative impact on equilibrium swelling and de-swelling ratio (about 700% and 15% decrease respectively). A viscoelastic, but close to elastic, behavior in both swelling and de-swelling equilibrium states under small-amplitude oscillatory shear was observed. The results of this work are expected to accelerate research in applications such as actuators and soft robotics.

Preparation of Immunotherapy Liposomal-Loaded Thermal-Responsive Hydrogel Carrier in the Local Treatment of Breast Cancer.

To reduce the side effects of immune drugs and the sustainable release of immune drugs on local parts, we have designed an injectable thermal-sensitive hydrogel containing an imiquimod-loaded liposome system. In the extracellular environment of tumor tissues (pH 6.4), 50% of the drug was released from the carrier, which could be a result of the morphological changes of the liposomal microstructure in the acidic environment. According to the results in animals, the drug-containing liposomes combined with hydrogel can be effectively applied in breast cancer therapy to delay the growth of tumors as well as to dramatically reduce the death rate of mice.

A dual synergistic of curcumin and gelatin on thermal-responsive hydrogel based on Chitosan-P123 in wound healing application

This study aimed to fabricate the potential therapeutic scaffold to efficiently and safely fastening skin wound healing. A biocompatible grafting polymer-based thermal sensitive hybrid hydrogel (Chitosan-P123, CP) containing gelatin and curcumin was designed to be suitable stiffness for tissue regeneration. A detailed in the rheological study found that the encapsulated agents induced the change in the stiffness of the hydrogel from the hard to the soft. Especial, the thermally induced phase transition of CP hydrogel was governed by the participant of gelatin rather than curcumin. For example, at 25 wt% gelatin, CP hydrogel exhibited a unique gel–sol-gel transition following the function of temperature. Moreover, in vitro investigation revealed that the hybrid hydrogel provides the capacity of especially induced curcumin release with a sustainable rate as well as the excellent biocompatibility scaffold. Altogether with in vivo study, the hybrid hydrogel highlighted the advance of the dual synergistic of curcumin and gelatin in development of smart scaffold system, which promoted the efficacy in the regeneration of the structure and the barrier's function of damaged skin such as wound or skin cancer.

Chiral, thermal-responsive hydrogels containing helical hydrophilic polyacetylene: preparation and enantio-differentiating release ability

Chiral hydrogels constructed from helical hydrophilic polyacetylene demonstrate chirality, thermo-responsivity, biocompatibility and enantio-selective release ability towards chiral drugs.

Enhanced photo/chemo combination efficiency against bladder tumor by encapsulation of DOX and ZnPC into in situ-formed thermosensitive polymer hydrogel.

BackgroundChemotherapy after transurethral resection is commonly recommended for bladder cancer. However, studies have shown that chemotherapy solely can hardly decrease progression rates of bladder cancer. The combination of chemotherapeutic agents with photo-dynamic therapy (PDT), a new promising localized therapy, may become a workable strategy for combating bladder cancer. This study reports the combination of doxorubicin (DOX)-based chemotherapy and zinc phthalocyanine (ZnPC)-based PDT using in situ-formed thermal-responsive copolymer hydrogel.Materials and methodsThe copolymer was synthesized by polymerization of 3-caprolactone, 1,4,8-trioxa[4.6]spiro-9-undecanone and poly(ethylene glycol) and was abbreviated as PCL-PTSUO-PEG. The thermal-responsive nanoparticles (TNPs) were prepared by the nanoprecipitation technology. The thermal-responsive hydrogel was formed after 37°C heating of TNP solution. The size, morphology and dynamic viscosity of hydrogel were detected. The in vitro drug release profile of TNP/DOX/ZnPC was performed. Cell uptake, cell inhibition and ROS generation of TNP/DOX/ZnPC were studied in 5637 cells. The in vivo antitumor activity of TNP/DOX/ZnPC was evaluated in nude mice bearing 5637 cells xenograft.ResultsTNP/DOX and TNP/ZnPC had an average diameter of 102 and 108 nm, respectively. After being heated at 37°C for 5 minutes, TNP/DOX and TNP/ZnPC solution turned uniform light red and dark green hydrogel. ZnPC encapsulation designed by TNP could significantly improve its aqueous solubility to 1.9 mg/mL. Cell inhibition showed that the best cell inhibition was found, with cell viability of 18.5%, when the weight ratio of DOX and ZnPC encapsulated in the TNP reached about 1:5. TNP/DOX/ZnPC generated relative high level of ROS with 4.8-fold of free ZnPC and 1.6-fold of TNP/ZnPC. TNP/DOX/ZnPC showed only 8-fold of relative tumor growth without obvious toxicity to the mice.ConclusionThermosensitive thermal-responsive hydrogel reported in this contribution are promising in situ-formed matrix for DOX- and ZnPC-based photo/chemo combination treatment for bladder cancer therapy.

Thermo-Sensitive PLGA-PEG-PLGA Tri-Block Copolymer Hydrogel as Three-Dimensional Cell Culture Matrix for Ovarian Cancer Cells.

Thermo-sensitive hydrogels which could encapsulate cells and provide a three dimensional (3D) microenvironment have great potential in building new cell culture models in vitro. In this study, a thermal responsive hydrogel based on PLGA-PEG-PLGA tri-block copolymers was developed as matrix for 3D ovarian cancer cell culturing. The gelation of PLGA-PEG-PLGA tri-block copolymer was concentration-dependent. SEM images showed the pores were suitable for the formation of 3D cell structures. Cell morphological results showed that large aggregates of ovarian cancer cells (HO8910) were formed after cultured for 10 days. Therefore, hydrogel based on PLGA-PEG-PLGA tri-block copolymers hold potential as in vitro cell culture matrix for ovarian cancer cells.

Design, Synthesis, Characterization, Swelling and in Vitro Drug Release Behavior of Composite Hydrogel Beads Based on Methotrexate and Chitosan Incorporating Antipyrine Moiety

ABSTRACTNovel biodégradable pH and thermal-responsive hydrogels were prepared for controlled drug delivery studies via reaction of chitosan with 4-chloroacetylantipyrine in DMF/H2O, followed by heating of the formed poly [acetylantipyrine-chitosan] with glutaraldehyde as a crosslinking agent to give the hydrogels. These hydrogels were subjected to equilibrium swelling studies at different temperatures (25°C, 37°C and 45°C) in solutions of pH 2.1 and 7.4. Methotrexate (MTX) was entrapped in the hydrogels, and drug release studies were carried out at 37 °C in solutions at pH 2.1 and 7.4.

Controllable thermal and pH responsive behavior of PEG based hydrogels and applications for dye adsorption and release.

A series of controllable thermal and pH dual-responsive copolymeric hydrogels (PMA) were prepared by a one-pot reaction with poly(ethylene glycol) methyl ether acrylate (PEGA), 2-methoxyethyl acrylate (MEA) and acroleic acid (AA). The hydrogels exhibited good mechanical properties and a sensitive response to pH and temperature. Besides, the Lower Critical Solution Temperature (LCST) of the hydrogels can be adjusted from 37 °C to 58 °C by changing the content of AA. The hydrogels also showed excellent selective adsorption properties. The maximum adsorption quantity of organic cationic dye brilliant green and methylene blue were 0.49 mg mg−1 and 0.42 mg mg−1 respectively, much better than previous reports. Furthermore, using the thermal and pH responsibility, the PMA hydrogels can release the adsorbed molecules with control. Nearly 95% of carriers could be released at pH 4.01 and 65 °C over 8 h. The regeneration ability makes the materials easy to reuse many times. Due to these properties, these dual-responsive hydrogels have great potential applications in various fields for adsorption, drug delivery, release and tissue engineering.

Dynamics retardation in hybrid POSS-NIPAm nanocomposites. Thermoplastic and thermally-responsive hydrogel behavior

A series of uncrosslinked and unentangled hybrid copolymers of N-isopropyl acrylamide (NIPAm) and polyhedral oligomeric silsesquioxane (POSS) exhibited dual, thermoplastic and hydrogel behavior. The products of the synthesis were characterized by nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The dried hybrids were amorphous and exhibited a reduction of glass transition temperature Tg as POSS content increased, i.e., ΔTg = Tg − Tg,bulk < 0°C, suggesting nanoconfinement-like effects. The hybrid melts exhibited linear viscoelastic behavior. Master curves were constructed using time–temperature superposition (TTS), and PNIPAm displayed Rouse dynamics. The hybrid melts however displayed terminal and transition regimes where the scalings G″ ≠ ω2 and G′ = G″ ≠ ω1/2, did not hold. The mechanical damping evidenced a molecular retardation mechanism suggesting POSS-POSS interactions in the melt. Strikingly, the melt viscosity was reduced up to one order of magnitude and exhibited yield stress at higher POSS content, a consequence of POSS associations. In the hydrated state the “sticky” POSS-POSS associations produced hydrogel behavior, with at least ∼3 wt% POSS content. The hydrogels were thermo-responsive, and POSS tuned the LCST, swelling ratio, and modulus. The physical associations are reversible as the hydrogels healed immediately after a nonlinear deformation. Hence, the thermoplastic-hydrogel behavior of PNIPAm-POSS hybrids enables thermoforming (injection molding, extrusion, and fiber spinning) followed by hydration. This bottom-up approach opens opportunities for easily procesable, environmentally friendly, and versatile smart hydrogel-based medical devices.

Thermally Responsive Composite Hydrogel via Self-Assembly for Smart Window Applications

A novel thermally responsive hydrogel (TRH) has been demonstrated by confining poly(ethylene oxide), poly(propylene oxide), and poly(ethylene oxide) triblock-copolymer (EPE) molecules into the pores of polymer framework. Aqueous EPE copolymer molecule had a tendency to aggregate to form clusters gradually and precipitated from water when the temperature is above a cloudy point. By adding EPE molecules into the acrylamide (AM) monomer solution, the mixture can be fabricated as uniform and transparent hydrogel via controlled radical polymerization. The polyacrylamide hydrogel is produced with a switchable optical property when subjecting to temperature variation. Such reversible thermally responsive material can be utilized as a functional material for smart window application. Additionally, the thermal responsive hydrogel is an inexpensive material, which is readily applicable as smart windows with significant reduction in material cost.

Light-, pH- and thermal-responsive hydrogels with the triple-shape memory effect

Light-, pH- and thermal-responsive hydrogels were prepared by introducing dansyl-aggregations and azo-cyclodextrin inclusion complexes as switches. The resulting material showed dual shape memory behavior in response to light, pH or temperature, respectively, and exhibits the triple-shape memory effect in response to light and pH sequentially.

A thermo-responsive dual-crosslinked hydrogel with ultrahigh mechanical strength

A thermal-responsive hydrogel with ultrahigh mechanical strength was engineered by a covalently cross-linked and an ionic coordinated network.