Thermoresponsive Hydrogel Research Articles

High-performance Marangoni hydrogel rotors with asymmetric porosity and drag reduction profile

Miniaturized rotors based on Marangoni effect have attracted great attentions due to their promising applications in propulsion and power generation. Despite intensive studies, the development of Marangoni rotors with high rotation output and fuel economy remains challenging. To address this challenge, we introduce an asymmetric porosity strategy to fabricate Marangoni rotor composed of thermoresponsive hydrogel and low surface tension anesthetic metabolite. Combining enhanced Marangoni propulsion of asymmetric porosity with drag reduction of well-designed profile, our rotor precedes previous studies in rotation output (~15 times) and fuel economy (~34% higher). Utilizing thermoresponsive hydrogel, the rotor realizes rapid refueling within 33 s. Moreover, iron-powder dopant further imparts the rotors with individual-specific locomotion in group under magnetic stimuli. Significantly, diverse functionalities including kinetic energy transmission, mini-generator and environmental remediation are demonstrated, which open new perspectives for designing miniaturized rotating machineries and inspire researchers in robotics, energy, and environment.

Thermoresponsive shear-thinning hydrogel (T-STH) hemostats for minimally invasive treatment of external hemorrhages.

Hemorrhage is the leading cause of death following battlefield injuries. Although several hemostats are commercially available, they do not meet all the necessary requirements to stop bleeding in combat injuries. Here, we engineer thermoresponsive shear-thinning hydrogels (T-STH) composed of a thermoresponsive polymer, poly(N-isopropyl acrylamide) (p(NIPAM)), and hemostatic silicate nanodisks, LAPONITE®, as minimally invasive injectable hemostatic agents. Our T-STH is a physiologically stable hydrogel that can be easily injected through a syringe and needle and exhibits rapid mechanical recovery. Additionally, it demonstrates temperature-dependent blood coagulation owing to the phase transition of p(NIPAM). It decreases in vitro blood clotting times over 50% at physiological temperatures compared to room temperature. Furthermore, it significantly prevents blood loss in an ex vivo bleeding model at different blood flow rates (1 mL min-1 and 5 mL min-1) by forming a wound plug. More importantly, our T-STH is comparable to a commercially available hemostat, Floseal, in terms of blood loss and blood clotting time in an in vivo rat liver bleeding model. Furthermore, once the hemorrhage is stabilized, our T-STH can be easily removed using a cold saline wash without any rebleeding or leaving any residues. Taken together, our T-STH can be used as a first aid hemostat to treat external hemorrhages in emergency situations.

Temperature responsive hydrogels for biomedical applications

Hydrogel is a three-dimensional communicator for water-insoluble chemicals. The hydrogel can swell structurally with water and contain large amounts of water. Hydrogel is a chemical or physicochemical bond in different polymer chains. Hydrogels are due to their high water content, softness, flexibleness, and biocompatibility. Hydrogels have therefore become increasingly popular. Hydrogels are created by physically or chemically complex natural and human hydrophilic polymers. When an environmentally specific stimulus is specific to the hydrogel, the gel replaces with solutions. Part of the advantage of universal action by thermo-responsive hydrogels is that they show their activity without the charge of any additional external factors. These hydrogels are attractive for specific medical applications because they can swell in place under physiological conditions and facilitate administration. Due to the combination of distinctly different properties of temperature-sensitive durability through joined domains and the high chemical conversion reactivity of nonmaterial, the application of temperature-sensitive hydrogels with the ion-exchange region for nanoscale chemical conversion reactions is an emerging and enticing alternative niche. The protection and direct fabrication of reactive palladium nanoparticles in temperature-responsive hydrogel networks are defined.

Thermoresponsive hydrogel for transcatheter arterial chemoembolization of hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is one of the most commonly used treatments for hepatocellular carcinoma (HCC); however, the poor stability of emulsified chemotherapy drugs by iodinated oil always leads to serious systemic cytotoxicity. Herein, a composite hydrogel Epi/Etpoil@MC/XG was proposed by stably distributing ethiodized poppyseed oil (Etpoil) and epirubicin (Epi) in the blend hydrogel of methylcellulose (MC) and xanthan gum (XG). Benefiting from its adjusted thermo-responsive and injectable properties, the Epi/Etpoil@MC/XG has been successfully applied in the embolization of the feeding artery for a VX2 tumor model.

A thermo-responsive hydrogel loaded with an ionic liquid microemulsion for transdermal delivery of methotrexate.

Systemic administration of methotrexate (MTX), the gold standard for the treatment of psoriasis, can cause adverse side effects. To address this issue, a thermally responsive hydrogel loaded with an ionic liquid microemulsion (IL-ME) was developed for the transdermal delivery of MTX. The microemulsion was prepared using water, Tween 20 and choline and geranic acid (CAGE) ionic liquid. The solubility of methotrexate in the IL-ME was 9-fold higher than that in phosphate buffer (PBS). The hydrogel (Gel) based on isopropylacrylamide and silk fibroin acts as a drug reservoir to achieve temperature-responsive drug release in the human epidermis. The loading of the IL-ME or MTX-containing IL-ME on the Gel produced a ME@Gel or MTX/ME@Gel. In vitro permeation experiments showed that the MTX/ME@Gel exhibited a 27.6% increase in MTX permeation. In addition, IL-ME exhibits strong antibacterial activity. In vivo studies indicated that when compared with the results obtained in PBS medium, the MTX/ME@Gel could effectively treat skin redness, swelling and scaling caused by imiquimod (IMQ). In general, the present study demonstrated that the MTX/ME@Gel provides vast potential to serve as a biocompatible drug carrier for the efficient delivery of poorly soluble drugs, i.e., MTX in this particular case.

Compressive molding of engineered tissues via thermoresponsive hydrogel devices.

Biofabrication of tissues requires sourcing appropriate combinations of cells, and then arranging those cells into a functionally-useful construct. Recently, organoids with diverse cell populations have shown great promise as building blocks from which to assemble more complex structures. However, organoids typically adopt spherical or uncontrolled morphologies, which intrinsically limit the tissue structures that can be produced using this bioassembly technique. Here, we develop microfabricated smart hydrogel platforms in thermoresponsive poly(N-isopropylacrylamide) to compressively mold microtissues such as spheroids or organoids into customized forms, on demand. These Compressive Hydrogel Molders (CHyMs) compact at cell culture temperatures to force loaded tissues into a new shape, and then expand to release the tissues for downstream applications. As a first demonstration, breast cancer spheroids were biaxially compacted in cylindrical cavities, and uniaxially compacted in rectangular ones. Spheroid shape changes persisted after the tissues were released from the CHyMs. We then demonstrate long-term molding of spherical brain organoids in ring-shaped CHyMs over one week. Fused bridges formed only when brain organoids were encased in Matrigel, and the resulting ring-shaped organoids expressed tissue markers that correspond with expected differentiation profiles. These results demonstrate that tissues differentiate appropriately even during long-term molding in a CHyM. This platform hence provides a new tool to shape pre-made tissues as desired, via temporary compression and release, allowing an exploration of alternative organoid geometries as building blocks for bioassembly applications.

Injectable thermoresponsive hydrogels based on (Me)PEG–poly(menthide) amphiphilic block copolymers from bioderived lactone

Synthesis of (Me)PEG–PM block copolymers from a sustainable source, (−)-menthone, and their thermoresponsive characteristics.

Thermoresponsive “irreversible” property change of POSS-crosslinked PNIPAAm hydrogels

Incorporation of a strongly hydrophobic component as a crosslinking point enables reversibility control of property change of thermoresponsive hydrogels.

Effect of thermo-responsive hydrogel on epidural anesthesia in Beagle dogs

Effect of thermo-responsive hydrogel on epidural anesthesia in Beagle dogs

Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing

Background: Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The objective of the current study was to formulate Epidermal Growth Factor loaded Chitosan nanoparticle impregnated with thermos-responsive injectable hydrogel with protease inhibitor. EGF, shown in all stages of wound healing from inflammation to proliferation and remodelling, combined with Doxycycline, a well-known anti-inflammatory and anti-bacterial drug, could be a better strategy in diabetic wound healing. However, EGF's low stability makes it difficult to use. Methodology: The nanoparticles were prepared using the ionic gelation method. The prepared nanoparticles were evaluated for particle size, zeta potential, entrapment efficiency, and SEM studies. Further, the optimized nanoparticle batch was loaded into hydrogel with a protease inhibitor. The hydrogel was evaluated for morphology, protease degradation, in vitro drug release, anti-bacterial activity, cell migration, in vitro cell biocompatibility, and in vivo wound healing studies. Results and Conclusion: The particle size analysis of nanoparticles revealed the size (203 ± 1.236 nm), Zeta potential (+28.5 ± 1.0 mV), and entrapment efficiency of 83.430 ± 1.8%, respectively. The hydrogel showed good porous morphology, injectability, thermo-responsive, biocompatibility, and controlled drug release. In vitro anti-bacterial studies revealed the potential anti-bacterial activity of doxycycline against various microbes. In vivo data indicated that combining EGF and DOX considerably reduced inflammation time-dependent than single-agent treatment. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis and a fully regenerated epithelial layer and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis, a fully regenerated epithelial layer, and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site.

Synthesis of thermoresponsive composite hydrogel from Pluronic F127 reinforced by oil palm empty fruit bunches-extracted cellulose for silver sulfadiazine drug delivery

Hydrogels are modern dermal drug-delivery media which can hold a huge amount of water and modify their structure to enable spontaneous response to temperature change and are thus attractive to overcome the limitations of conventional drug-delivery media. In this study, a sustainable method was developed to synthesize thermoresponsive Pluronic F127 (PF127) composite hydrogel reinforced by cellulose extracted from oil palm empty fruit bunches (OPEFBs). The thermoresponsive cellulose/PF127 composite hydrogels were formulated by dissolving OPEFB-extracted cellulose in aqueous sodium hydroxide/urea solution prior to mixing with PF127 polymer at low temperature. The performance of the synthesized thermoresponsive cellulose/PF127 composite hydrogels was evaluated in terms of their swelling ratio, percentage of degradation, and in vitro silver sulfadiazine (AgSD) drug release. PCT20 thermoresponsive cellulose/PF127 composite hydrogel with 20 w/v% PF127 and 3 w/v% OPEFB cellulose showed high mechanical strength (storage modulus and complex viscosity values of 20.90 kPa and 2.09 kPa s, respectively), relatively high swelling ratio (3.63 ± 0.43), and prolonged release of AgSD (t50% value of 4 h) compared with PCT17-PCT19 thermoresponsive cellulose/PF127 composite hydrogels. Besides, AgSD-loaded thermo-responsive cellulose/PF127 composite hydrogels showed relatively good inhibitory activity against the Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Streptococcus pyogenes, and Klebsiella pneumoniae bacteria. The exploration of thermoresponsive cellulose/PF127 composite hydrogel from OPEFBs can promote sustainable, environment-friendly, and cost-effective drug delivery systems by using abundant agricultural biomass.

A Review on Thermal Properties of Hydrogels for Electronic Devices Applications.

Hydrogels, as a series of three-dimensional, crosslinked, hydrophilic network polymers, exhibit extraordinary properties in softness, mechanical robustness and biocompatibility, which have been extensively utilized in various fields, especially for electronic devices. However, since hydrogels contain plenty of water, the mechanical and electrochemical properties are susceptible to temperature. The thermal characteristics of hydrogels can significantly affect the performance of flexible electronic devices. In this review, recent research on the thermal characteristics of hydrogels and their applications in electronic devices is summarized. The focus of future work is also proposed. The thermal stability, thermoresponsiveness and thermal conductivity of hydrogels are discussed in detail. Anti-freezing and anti-drying properties are the critical points for the thermal stability of hydrogels. Methods such as introducing soluble ions and organic solvents into hydrogels, forming ionogels, modifying polymer chains and incorporating nanomaterials can improve the thermal stability of hydrogels under extreme environments. In addition, the critical solution temperature is crucial for thermoresponsive hydrogels. The thermoresponsive capacity of hydrogels is usually affected by the composition, concentration, crosslinking degree and hydrophilic/hydrophobic characteristics of copolymers. In addition, the thermal conductivity of hydrogels plays a vital role in the electronics applications. Adding nanocomposites into hydrogels is an effective way to enhance the thermal conductivity of hydrogels.

Dual thermo-responsive multifunctional ionic conductive hydrogel by salt modulation strategy for multilevel encryption and visual monitoring

Despite the current progress in thermo-responsive materials, it is still a significant challenge to develop superior multiple temperature-sensitive ionic conductive hydrogels with programmable regulation capability for interactive wearable iontronics. Here, a dual thermo-responsive ionic conductive hydrogel (DTICH) is constructed based on a salt modulation strategy, which cleverly integrates low-temperature sensitive sodium dodecyl sulfate (SDS) and high-temperature sensitive poly(N-isopropylacrylamide) PNIPAm-based polymer. Owing to the common ion effect and salting-out effect, the resultant DTICH hydrogel visually presents wide and tunable dual temperature response behaviors of 0-18℃ (Tk) and 37-80℃ (LCST) by controlling NaCl concentration for the first time. Meanwhile, benefiting from the synergy of NaCl and thermo-sensitive materials, the hydrogel is concurrently endowed with excellent stretchability (>900 %), adhesion (adhesion strength >30 kPa), frost resisting (-40℃) and multilevel encryption functions. More importantly, the DTICH hydrogel can ingeniously perceive mechanical force and external temperature via the changes of relative resistance and transparency, which can be applied as human–computer interfaces to interactively monitor human motions and temperatures in real time. Therefore, our study establishes a brand new and effective route for the rational design and fabrication of high-level visual interactive devices and smart wearable iontronics.

Mammalian cell encapsulation in monodisperse chitosan beads using microchannel emulsification

Microchannel emulsification can produce droplets of uniform size at high throughput for wide-ranging applications in the food and drug industry. Mammalian cell encapsulation using emulsion-based systems is of significant interest for immobilized culture or transplantation applications. Microchannel emulsification has recently been applied to mammalian cell encapsulation using alginate. Here, we extend this approach to thermoresponsive hydrogels using chitosan as a model. The performance of the microchannel emulsification process was compared to a previously established stirred emulsification method for mesenchymal stromal cell encapsulation. Chitosan microbeads with controlled sizes ranging from 600 µm to 1500 µm in diameter at a coefficient of variation less than 10 % were obtained after adapting the microchannel system design, channel geometries and operating parameters that affect the capillary number. In a single pass through a 21 G syringe needle, the fraction of ruptured beads was significantly reduced for monodisperse microchannel-generated vs polydisperse stirred emulsion-generated beads of matching De Brouckere mean diameter. The viability of the immobilized cells immediately after the process was 95 % ± 2 % and no significant difference in cell survival and growth factor secretion was observed between microchannel and stirred emulsion-generated beads over 3 days of culture. Microchannel emulsification is a promising and scalable approach to microencapsulate mammalian cells in hydrogels that undergo temperature-dependent gelation.

Untethered unidirectionally crawling gels driven by asymmetry in contact forces

Reversible thermoresponsive hydrogels, which swell and shrink (deswell) in the temperature range of 30° to 60°C, provide an attractive material class for operating untethered soft robots in human physiological and ambient conditions. Crawling has been demonstrated previously with thermoresponsive hydrogels but required patterned or constrained gels or substrates to break symmetry for unidirectional motion. Here, we demonstrate a locomotion mechanism for unidirectionally crawling gels driven by spontaneous asymmetries in contact forces during swelling and deswelling of segmented active thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) and passive polyacrylamide (pAAM) bilayers with suspended linkers. Actuation studies demonstrate the consistent unidirectional movement of these gel crawlers across multiple thermal cycles on flat, unpatterned substrates. We explain the mechanism using finite element simulations and by varying experimental parameters such as the linker stiffness and the number of bilayer segments. We elucidate design criteria and validate experiments using image analysis and finite element models. We anticipate that this mechanism could potentially be applied to other shape-changing locomotors.

A MgFe-LDH Nanosheet-Incorporated Smart Thermo-Responsive Hydrogel with Controllable Growth Factor Releasing Capability for Bone Regeneration.

Although growth factor (GF)-loaded hydrogels have been explored as promising materials in repairing bone defects, it still remains challenging to construct smart hydrogels with excellent gelation/mechanical properties as well as controllable GF releasing capability. Herein, the incorporation of bone morphogenetic protein 2 (BMP-2)-functionalized MgFe-layered double hydroxide (LDH) nanosheets into chitosan/silk fibroin (CS) hydrogels loaded with platelet-derived growth factor-BB (PDGF-BB) to construct a smart injectable thermo-responsive hydrogel (denoted as CSP-LB), which can achieve a burst release of PDGF-BB and a sustained release of BMP-2, for highly efficient bone regeneration is reported. The incorporation of MgFe-LDH in CS hydrogel not only shortens the gelation time and decreases sol-gel transition temperature, but also enhances the mechanical property of the hydrogel. Because of the sequential release of dual-GFs and sustained release of bioactive Mg2+ /Fe3+ ions, the in vitro experiments prove that the CSP-LB hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CS hydrogel. In vivo experiments further prove that the CSP-LB hydrogel can significantly enhance bone regeneration with higher bone volume and mineral density than that of the CS hydrogel. This smart thermo-sensitive CSP-LB hydrogel possesses excellent gelation capability and angiogenic and osteogenic properties, thus providing a promising minimally invasive solution for bone defect treatment.

Solar Light Management Enabled by Dual-Responsive Smart Window

Smart windows with tunable optical properties for energy-saving and privacy protection applications are receiving increasing attention. However, current studies of smart windows either involve the use of complex material preparation processes and complex device systems for window switching or continue to face several challenges, including low luminous transmittance, low luminous and solar modulation, and narrow wavelength range management problems. Here, we report a dual-responsive smart window that achieves solar light management in the range of 200-2500 nm. This smart window is fabricated by combining a reversible thermoresponsive hydrogel that acts as a thermochromic material with a ZnO/Ag/ZnO multilayer film that acts as a transparent heater. The as-prepared smart window can modulate solar light over a range from ultraviolet to infrared and achieves active responses to high-temperature weather, with passive responses being produced through electrical heating. The smart window shows high luminous transmittance (81.7%) and high luminous modulation (81.6%), together with an outstanding solar modulation performance (62.9%). In outdoor demonstrations, the as-prepared smart window exhibited a promising temperature regulation ability under strong solar irradiation. Therefore, the proposed smart window promises to provide a simple and effective energy management technology for buildings.

Combining thermosensitive physical self-assembly and covalent cycloaddition chemistry as simultaneous dual cross-linking mechanisms for the preparation of injectable hydrogels with tuneable properties

Injectable hydrogels are promising materials for the sustained delivery of therapeutics, bioactives and cell therapies. Hydrogels that display suitable processing times and rapid gelling kinetics upon injection are particularly desirable as they can limit burst release of their payload. Therefore, we aimed to develop hydrogels that could be readily processed at ambient temperature, gelled rapidly at physiological temperature, and possessed tuneable properties (e.g., degradation and release profiles). To achieve this, a unique dual cross-linking mechanism was investigated, employing a combination of pentafulvene-maleimide Diels-Alder cycloaddition (DAC) chemistry and thermoresponsive physical cross-linking with a functionalised poly(ethylene glycol-b-propylene glycol-b-ethylene glycol) (PEG-PPG-PEG; Pluronic F-127) copolymer. A combination of temperature dependent nuclear magnetic resonance spectroscopy, dynamic light scattering, and rheological measurements were conducted to interrogate the gelation mechanism. Whereas the reaction between aqueous solutions of maleimide functionalised Pluronic and pentafulvene functionalised PEG star polymer resulted in hydrogels with gelation times (tgel) between 30 and 55 mins at ambient temperature, significantly faster tgel values (5–10 mins) were observed at physiological temperatures (37 °C). The relatively slow gelation at ambient temperature provided good working times and injectability through narrow gauge (261/2 G) needles. While the initial Young’s modulus (E) of the hydrogels was highly dependent on the gelation temperature, the E remained dynamic in response to further temperature changes post-gelation. The hydrogels displayed relatively low swelling (20–30% mass increases) and degradation times (td) up to 16 d, which provided for the sustained release of latex particles (cell mimic) over a period of 7–14 d. With their tuneable gelation kinetics and properties, the thermoresponsive DAC hydrogels have potential for the controlled release of therapeutics.

Exploration of hemocompatibility and intratumoral accumulation of paclitaxel after loco-regional administration of thermoresponsive hydrogel composed of poloxamer and xanthan gum: An application to dose-dense chemotherapy

Although paclitaxel is a front-line chemotherapeutic agent for the treatment of metastatic breast cancer, its intravenous therapy produces deleterious adverse effects. In an attempt to address the issue, the present study aimed to develop a paclitaxel loaded thermosensitive/thermoresponsive hydrogel (PTXNp-TGel) for loco-regional administration to breast tumors to provide dose-dense chemotherapy. Poloxamer and xanthan gum were used to prepare TGel by the cold method. In vitro and in vivo performance of PTXNp-TGel was compared with TGel, pure drug loaded TGel (PTX-TGel) and marketed formulation, Taxol®. The formulated PTXNp-TGel showed acceptable gelation temperature and time (37 °C and 57 s), lower viscosity at room temperature and higher viscosity at body temperature to support sol-gel transition with increasing temperature, and sustained drug release up to 21 days. Additionally, PTXNp-TGel showed negligible hemolytic toxicity as compared to PTX-TGel and Taxol®. Intratumoral administration of PTXNp-TGel produced significantly higher antitumor activity as indicated by lowest relative tumor volume (1.50) and relative antitumor proliferation rate (27.71 %) in comparison with PTX-TGel, Taxol®, and PTXNp (p < 0.05). Finally, insignificant body weight loss during the experimental period, lack of hematotoxicity, nephrotoxicity, and hepatotoxicity imply improved therapeutic performance of the locally administrated dose-dense therapy of PTXNp-TGel as compared to Taxol®.

Injectable Composite Systems of Gellan Gum:Alginate Microparticles in Pluronic Hydrogels for Bioactive Cargo Controlled Delivery: Optimization of Hydrogel Composition based on Rheological Behavior

Due to the high complexity of some treatments, there is a need to develop drug-delivery systems that can release multiple drugs/bioactive agents at different stages of treatment. In this study, a thermoresponsive injectable dual-release system was developed with gellan gum/alginate microparticles (GG:Alg) within a thermoresponsive Pluronic hydrogel composed of a mixture of Pluronic F127 and F68. The increase in F68 ratio and decrease in F127 lead to higher transition temperatures. The addition of the GG:Alg microparticles decreased the transition temperatures with a linear tendency. In Pluronic aqueous solutions (20 wt.%), the F127:F68 ratios of 16:4 and 17:3 (wt.%:wt.%) and the addition of microparticles (up to 15 wt.%) maintained the sol–gel transition temperatures within a suitable range (between 25 °C and 37 °C). Microparticles did not hinder the injectability of the system in the sol phase. Methylene blue was used as a model drug to evaluate the release mechanisms from microparticles, hydrogel, and composite system. The hydrogel delayed the release of methylene blue from the microparticles. The hydrogel loaded with methylene blue released at a faster rate than the microparticles within the hydrogel, thus demonstrating a dual-release profile.