Temperature-responsive Hydrogel Research Articles

Temperature-Responsive Hydrogel Carrier for Reducing Adsorption Loss of Petroleum Sulfonates.

As an effective anionic surfactant for chemical flooding, petroleum sulfonate (PS) is often used in conjunction with alkalis to reduce the adsorption loss of PS onto rock and clay surfaces. However, alkali injection can lead to scaling, aggravate the water-sensitive effect of clays, and accelerate polymer hydrolysis. Here, a temperature-responsive biohydrogel-based carrier (XLK) was designed to protect PS from adsorption onto geological features. XLK, an aqueous mixture containing 0.5% xanthan gum, 0.5% locust bean gum, and 2% KCl, was a gel at room temperature and transformed gradually into a sol above 50 °C (sol/gel transition temperature, Tsol/gel). Below the Tsol/gel, most PS was retained in the gel, preventing the adsorption of PS onto quartz sand. Above the Tsol/gel, PS was released into the surrounding medium. After it had been loaded with PS, the storage modulus (G', Pa) of XLK increased from 102 to 103 and the loss modulus (G″, Pa) increased from 101 to 102. Environmental scanning electron microscopy micrographs showed that PS filled gaps within the cross-linked network structure of XLK. Compared with the aqueous XLK formulation, the addition of hydrolyzed polyacrylamide (HPAM) decreased the melt rate of XLK and the interfacial tension (IFT) of PS. Among the constituents of XLK loaded with PS, KCl had the most obvious effect of lowering the shear modulus of HPAM. Sufficient amounts of KCl were effective in reducing the IFT of PS to ultralow levels (10-3 mN/m).

Tracking Control of a Miniature 2-DOF Manipulator With Hydrogel Actuators

Due to the nature of the complex spatiotemporal dynamics of stimuli-responsive soft materials, closed-loop control of hydrogel-actuated mechanisms has remained a challenge. This letter demonstrates, for the first time, closed-loop trajectory tracking control in real-time of a millimeter-scale, two degree-of-freedom manipulator via independently-controllable, temperature-responsive hydrogel actuators. A linear state-space model of the manipulator is developed from input-output measurement data, enabling the straightforward application of control techniques to the system. The Normalized Mean Absolute Error (NMAE) between the modeled and measured displacement of the manipulator's tip is below 10%. We propose an Observer-based controller and a robust H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> -optimal controller and evaluate their performance in a trajectory tracking output-feedback framework, compared with and without sinusoidal disturbances and noise. We demonstrate in simulation that the H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> -optimal controller, which is computed using Linear Matrix Inequality (LMI) methods, tracks an elliptical trajectory more accurately than the Observer controller and is more robust to disturbances and noise. We also show experimentally that the H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> -optimal controller can be used to track different trajectories with an NMAE below 15%, even when the manipulator is subject to a 3 g load, 12.5 times an actuator's weight. Finally, a payload transport scenario is presented as an exemplar application; we demonstrate that an array of four manipulators is capable of moving a payload horizontally by applying the proposed H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> -optimal trajectory-tracking controller to each manipulator in a decoupled manner.

In vivo evaluation of temperature-responsive antimicrobial-loaded PNIPAAm hydrogels for prevention of surgical site infection.

Surgical site infections (SSIs) are a persistent clinical challenge. Local antimicrobial delivery may reduce the risk of SSI by increasing drug concentrations and distribution in vulnerable surgical sites compared to what is achieved using systemic antimicrobial prophylaxis alone. In this work, we describe a comprehensive in vivo evaluation of the safety and efficacy of poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ], an injectable temperature-responsive hydrogel carrier for antimicrobial delivery in surgical sites. Biodistribution data indicate that PNDJ is primarily cleared via the liver and kidneys following drug delivery. Antimicrobial-loaded PNDJ was generally well-tolerated locally and systemically when applied in bone, muscle, articulating joints, and intraperitoneal space, although mild renal toxicity consistent with the released antimicrobials was identified at high doses in rats. Dosing of PNDJ at bone-implant interfaces did not affect normal tissue healing and function of orthopedic implants in a transcortical plug model in rabbits and in canine total hip arthroplasty. Finally, PNDJ was effective at preventing recurrence of implant-associated MSSA and MRSA osteomyelitis in rabbits, showing a trend toward outperforming commercially available antimicrobial-loaded bone cement and systemic antimicrobial administration. These studies indicate that antimicrobial-loaded PNDJ hydrogels are well-tolerated and could reduce incidence of SSI in a variety of surgical procedures.

3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications.

Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept®, OCT) possess accurate printability and shape fidelity. This study also provides the protocol of ink’s use for the 3D printing of hydrogel scaffolds. The hydrogel’s physicochemical properties and drug release profiles from the hydrogel specimens to the external solution have been determined at two temperatures (20 and 37 °C). The release test showed a sustained OCT delivery into ultrapure water and the PBS solution. The temperature-responsive hydrogel exhibited antimicrobial activity against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa and demonstrated non-cytotoxicity towards fibroblasts. The thermoresponsive behavior along with biocompatibility, antimicrobial activity, and controlled drug release make this hydrogel a promising class of materials for wound dressing applications.

Nonturbid Fast Temperature-Responsive Hydrogels with Homogeneous Three-Dimensional Networks by Two Types of Star Polymer Synthesis Methods

Nonturbid Fast Temperature-Responsive Hydrogels with Homogeneous Three-Dimensional Networks by Two Types of Star Polymer Synthesis Methods

Interference-based wide-range dynamic tuning of the plasmonic color of single gold nanoparticles.

Dynamic tuning of nanoscale coloration by exploiting localized surface plasmon resonance of gold nanoparticles (AuNPs) combined with an interference coloration mechanism is demonstrated experimentally. When interference between the scattering field from AuNPs and the reflected field from the substrate is observed under back-scattering white-light microscopy, the AuNPs exhibit various colors depending on their distance to the substrate. When the numerical aperture of the microscope objective is optimized, much greater coverage of the color space than was achieved with previously reported plasmon-based approaches is attained. Also, color tunability is examined by exploiting the temperature-induced volume change of a temperature-responsive hydrogel with embedded AuNPs to dynamically modify the distance to the substrate.

Tough thermosensitive hydrogel with excellent adhesion to low-energy surface developed via nanoparticle-induced dynamic crosslinking

Stimuli-responsive adhesive hydrogels have obtained increasing attention due to their applications in drug delivery and wearable sensors. However, these hydrogels exhibit weak mechanical properties and poor adhesion, especially on low-energy surfaces. Here, a temperature-responsive adhesive hydrogel was developed based on mussel-inspired dopamine chemistry and core–shell nanoparticle-regulated dynamic cross-linking. Poly(N-isopropylacrylamide) (PNIPAM) was used as the hydrogel skeleton, and it endowed the hydrogel with intelligent thermal sensitivity. Core-shell nanoparticles (NPs) with well-controlled sizes were synthesized through reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization. The NPs served as dynamic cross-linking cores and greatly improved the adhesion and mechanical properties of the hydrogel. In particular, the adhesive strength of PNIPAM-PDA-NP hydrogel on PTFE reached 10.3 kPa, and the maximum compressive strength was measured to be 3.41 MPa when being compressed by 90% of its volume. This study provides a novel strategy to develop high-performance stimuli-responsive adhesive hydrogels.

Nanofibrous hydrogels embedded with phase-change materials: Temperature-responsive dressings for accelerating skin wound healing

Wound environment-responsive materials show great potential in skin repair. Herein, a temperature-responsive fibrous hydrogel was developed with the aid of the phase-change material of natural fatty acids. The extracellular matrix-like methacrylate gelatin (GelMA) nanofibrous hydrogels were fabricated via electrospinning and UV-crosslinking, followed by a depot of fatty acids/aspirin (ASP) encapsulated polydopamine (PDA). The as-prepared fibrous hydrogels showed a significantly faster ASP release at 40 °C compared with those of 25 °C and 37 °C, and an “on-off” drug release was achieved at heating and cooling cycles between 40 °C and 25 °C. The in vitro cell culture tests and in vivo wound healing study proved that GelMA-PDA-ASP nanofibrous hydrogels facilitated the cell growth and accelerated wound repair. Taken together, the thermosensitive drug-releasing nanofibrous hydrogel, showed a great potential for wound care.

Multiresponsive Photonic Microspheres Formed by Hierarchical Assembly of Colloidal Nanogels for Colorimetric Sensors

Soft photonic materials formed from nanoscale colloidal crystals are versatile platforms for sensing and signaling in biomedical, chemical, and mechanical application scenarios. A particularly leveraged attribute of such materials is structural coloration; when applied in reconfigurable systems, dynamic coloration can be achieved, akin to the ability of chameleons to change their color appearance through nanocrystal structures beneath their skin. To date, many hybrid photonic materials composed of hard, passive, and soft adaptable systems have been explored for their dynamic color-changing performance; however, a lack of multifunctional and fully adaptable systems with sufficient control of properties on nanoscale persists. In addition, in hybrid systems with multiple stimuli-responsive components, interactions among components tend to be overlooked. Here, we propose a facile and scalable method to prepare multiresponsive photonic materials composed of soft and adaptable components, to tune the structural coloration over the entire visible spectral range. Temperature-responsive hydrogel microspheres of diameters of several tens of microns host an array of pH-responsive colloidal nanogels; the hierarchical assembly of nanogels scaffolded within the hydrogel microspheres form soft photonic microspheres that display a dynamic color change spanning the entire visible spectral range, through a variation in pH or temperature. pH change triggers a volume change in the nanogels, as does temperature change in the scaffolding hydrogel. A model predicting the equilibrium sizes of the microspheres as a function of temperature and pH has been proposed and validated. We also discuss the mutual interactions between the colloidal nanogels and the scaffolding hydrogel. These photonic microspheres could be applied as optically interrogated sentinels in label-free multiplexed chemical, thermal, and mechanical sensing with sub-millimeter resolution.

Population pharmacokinetic analysis of ropivacaine extended-release from a temperature-responsive hydrogel in rats.

Therapeutic agents with a short half-life need to be administered frequently to achieve sustained and effective concentrations. This could be accomplished using sustained drug delivery technology. PF-72 (TGel Bio, Inc., Seoul, Korea) is a drug delivery system based on a powder obtained from lyophilisation of a reverse thermal hydrogel, which could assist in achieving prolonged pain relief if mixed with an anaesthetic and injected into the incision site following surgery. The pharmacokinetic parameters related to the absorption of the local anaesthetic ropivacaine delivered using this hydrogel were quantified. Ten rats were divided into two groups (n=5 each), and equal doses (4mg/kg) of different formulations were subcutaneously injected into the abdomen. The experimental group received PF-72 mixed with 0.75% ropivacaine, and the control group received 0.75% ropivacaine. Blood was collected at specific times to measure the plasma concentration of ropivacaine. Population pharmacokinetic analysis was performed using NONMEM VII level 4 (ICON Development Solutions, Dublin, Ireland). The one-compartment absorption model, which combines zero-order absorption and first-order absorption, was used to describe the change in ropivacaine plasma concentration over time. The type of formulation was a significant covariate for zero-order absorption duration (experimental group, 92.9min; control group, 60.5min). The addition of PF-72 to 0.75% ropivacaine increased the duration of absorption into the blood, suggesting a longer lasting effect of the analgesic injected into the surgical wound.

One-step harvest and delivery of micropatterned cell sheets mimicking the multi-cellular microenvironment of vascularized tissue

Techniques for harvest and delivery of cell sheets have been improving for decades. However, cell sheets with complicated patterns closely related to natural tissue architecture were hardly achieved. Here, we developed an efficient method to culture and harvest cell sheets with complex shape (noted as microtissues) using temperature-responsive hydrogel consisting of expandable polyethylene oxide polymer at low temperature. Firstly, a temperature-responsive hydrogel surface with honeycomb patterns (50 and 100 µm in width) were developed through microcontact printing of polydopamine (PD). The human dermal fibroblasts (HDFBs) and human umbilical vein endothelial cells (HUVECs) spontaneously formed honeycomb-shaped microtissues on the patterned hydrogel surface. The microtissues on the hydrogel were able to be harvested and directly delivered to the desired target through thermal expansion of the hydrogel at 4 °C with an efficiency close to 80% within 10 min which is faster than conventional method based on poly(N-isopropylacrylamide). The microtissues maintained their original honeycomb network and intact structures. Honeycomb-patterned cell sheets also were fabricated through serial seeding of various cell lines, including HDFBs, HUVECs, and human adipose-derived stem cells, in which cells were attached along the honeycomb pattern. The underlying honeycomb patterns in the cell sheets were successfully maintained for 3 days, even after delivery. In addition, patterned cell sheets were successfully delivered in vivo while maintaining an intact structure for 7 days. Together, our findings demonstrate that micropatterned temperature-responsive hydrogel is an efficient method of one-step culturing and delivery of complex microtissues and should prove useful in various tissue engineering applications. Statement of significanceScaffold-free cell delivery techniques, including cell sheet engineering, have been developed for decades. However, there is limited research regarding culture and delivery of microtissues with complex architecture mimicking natural tissue. Herein, we developed a micro-patterned hydrogel platform for the culture and delivery of honeycomb-shaped microtissues. Honeycomb patterns were chemically engineered on the temperature-responsive hydrogel through microcontact printing of polydopamine to selectively allow for human dermal fibroblast or human umbilical vein endothelial cell adhesion. They spontaneously formed honeycomb-shaped microtissues within 24 hr upon cell seeding and directly delivered to various target area including in vivo via thermal expansion of the hydrogel at 4 °C, suggesting that the micro-patterned hydrogel can be an efficient tool for culture and delivery of complex microtissue.

Reduction and temperature-responsive hydrogel composed of hydroxyethyl disulfide-bis-glycidyl ether-crosslinked poly(hydroxyethyl acrylate-co-methyl methacrylate)

Reduction and temperature-responsive gels were prepared by crosslinking poly(hydroxyethyl acrylate-co-methyl methacrylate) (poly(HEA-co-MMA)) using hydroxyethyl disulfide-bis-glycidyl ether(HEDSGE) as a disulfide cross-linker. Poly(HEA-co-MMA) exhibited lower critical solution temperature (LCST) behavior when MMA content was 7.4 and 8.3 mole %. Energy dispersive X-ray and Raman spectroscopy revealed that the copolymer chains of the gels were cross-linked by disulfide bond (i.e., HEDSGE). The gels released their content in proportion to the concentration of a reducing agent (i.e., dithiothreitol). In addition, the gels released their payloads in a temperature dependent manner, possibly due to the LCST property of the copolymer. Highlights Reduction and thermo-responsive gels were prepared by crosslinking poly(HEA-co-MMA) using HEDSGE. Poly(HEA-co-MMA) exhibited LCST behavior when MMA content was 7.4 mole % and 8.3 mole %. Gels released their content in proportion to dithiothreitol (a reducing agent) concentration. Gels released their payloads in a temperature dependent manner.

In-situ grafting temperature-responsive hydrogel as a bifunctional solid-phase microextraction coating for tunable extraction of biomacromolecules

A temperature-responsive solid-phase microextraction (SPME) coating was prepared via in-situ atom transfer radical polymerization (ATRP) method. By controlling the temperature of solution below and above the lower critical solution temperature (LCST) of the coating, it can switch between hydrophilic and hydrophobic, thus providing a convenient approach for the selective extraction of analytes with different polarities. The average extraction amount of temperature-responsive coating for polar analytes is about 1.5-fold to that of non-polar ones below LCST, and vice versa. Effective extraction of three biomacromolecules was also obtained by controlling the temperature below or above LCST. The adsorption capacity of the coating for the hydrophilic biomacromolecules at 15 °C is 1.5-2 folds that of 50 °C, whereas the adsorption capacity of the coating to BSA at 50 °C is about 3 folds that of 15 °C. This approach holds great promise for SPME because it provides a simple strategy to prepare bifunctional coatings for various applications.

Temperature-Responsive On-Off Control over Water Evaporation Achieved via Sweat-Gland-Mimetic Composites.

Responsive cooling materials that mimic sweat glands have gained popularity because they are efficient and do not require artificial energy sources. Temperature-responsive hydrogels sweat above their volume transition temperature through the release of water and exhibit excellent cooling ability. However, thus far, practical applications have not been possible because the water in these materials cannot be preserved in cool environments. To address this issue, this paper presents a simple composite of poly(N-isopropylacrylamide) and polydimethylsiloxane that offers excellent on-off control over water evaporation and can be used repeatedly; the proposed composite features an evaporation rate of 2.97 g/h above the lower critical solution temperature (LCST) and 0.08 g/h below the LCST. This 35.7-fold change in the water evaporation rate is comparable to that in mammalian sweat glands. The responsive on-off control relies on the structures of the composite and the dry layers formed on the surface of the composite in cool environments. The proposed material effectively regulates water evaporation and offers a novel, low-cost cooling strategy suitable for numerous applications.

Physiologically relevant pH- and temperature-responsive polypeptide hydrogels with adhesive properties

Physiologically relevant pH- and temperature-responsive polypeptide hydrogels with adhesive properties were developed and characterized.

Kinetics of swelling of cylindrical functionally graded temperature-responsive hydrogels

Cylindrical hydrogels have a wide variety of applications in microfluidics; for example, they serve as micro-valves, micro-mixers, and micro-lenses. The main advantages of them can be mentioned as their autonomous functionality due to their responses to environmental stimuli and simple geometry. Furthermore, functionally graded hydrogels have recently found applications in hydrogel actuators. Therefore, in this work, the kinetics of swelling, shrinking, and force generation of cylindrical functionally graded temperature-responsive hydrogels are investigated. Kinetics of cylindrical structure is investigated analytically by developing a mathematical model based on available constitutive models of large deformation of hydrogels. The cross-link density of the hydrogel polymeric network varies along the radius of the cylinder linearly. In order to analyze the structure's behavior, the temperature is changed, and the response time of the structures with different distribution of cross-link density is investigated. In addition, to investigate the realistic actuators' performance, the cylindrical hydrogel is located inside a hollow cylinder, and the pressure of the hydrogel, which puts on the cylinder, is investigated. The results show that manipulation of cross-link density influences the response time of the cylindrical hydrogel; hence, it is a useful tool to manage the overall performance of cylindrical actuators.

A Novel Temperature‐Dependent Hydrogel Emulsion with Sol/Gel Reversible Phase Transition Behavior Based on Polystyrene‐co‐poly(N‐isopropylacrylamide)/Poly(N‐isopropylacrylamide) Core–Shell Nanoparticle

As a kind of temperature-responsive hydrogel, polystyrene-co-poly(N-isopropylacrylamide)/poly(N-isopropylacrylamide) (PS-co-PNIPAM/PNIPAM) core-shell nanoparticles prepared by two-step copolymerization are widely studied and used because of their specific structures and properties. Unlike most reports about the steady stability of PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion, in this work, the PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion (symbolized as PS/PNIPAM hydrogel emulsion), which is prepared after the second step of synthesis and without washing out a large number of PNIPAM polymer segments, shows a reversible temperature-dependent sol-gel transition characteristic during the temperature range of 34-80 °C. The PS/PNIPAM hydrogel emulsion is a normal solution at room temperature, and it changes from a sol to a gel statue when the temperature approaches up to low critical solution temperature (LCST). As the temperature continues to increase, the gel (core-shell nanoparticles as the crosslinkers and the linear PNIPAM chain as the 3D gel network) of the PS/PNIPAM hydrogel emulsion gradually shrinks and drains linearly. Compared with most crosslinked hydrogels, the hydrogel here can be arbitrarily changed in shape according to use needs, which is convenient for use, transportation, and storage. Here a new route is provided for the preparation of a PS/PNIPAM core-shell hydrogel nanoparticle system, as well as a new supramolecular crosslinking sol-gel system for application in biomedical materials, sensors, biological separation, drug release, macromolecular adsorption, and purification.

Magnetic Resonance Monitoring of Opaque Temperature-Sensitive Polymeric Scaffolds

The monitoring of location and degradation rates of injectable biomaterials is an area of particular interest in the design and implementation of therapeutic scaffolds and carriers for tissue repair and replacement. We describe here the fabrication and characterization of gadolinium (Gd)-labeled temperature-responsive hydrogels that can be detected noninvasively using T1-weight magnetic resonance. Two acrylamide-functionalized GdIIIDOTA-monoamide complexes with either a short n-butylene spacer (GdIII-C4-AA) or a long hydrophilic spacer (GdIII-PEG-AA) were synthesized and incorporated into the hydrogels. At temperatures above the lower critical solution temperature (LCST), 37 °C, these hydrogels have the capacity to enhance relaxivity (r1) due to the hydrophobic interactions of the polyamide chains around the gadolinium chelates. This effect is further accentuated by the presence of the polyethylene glycol groups of the Gd complex GdIII-PEG-AA.

Temperature-responsive self-lubricating hydrogel from dynamic Diels-Alder crosslinking for reservoir in-depth profile control

Deep formation layer is of high temperature, heterogeneity and oil saturation. Therefore, the gel for its profile control should have large strength, good migration and temperature tolerance performance in formation. In this work, a temperature-responsive self-lubricating hydrogel PAFB, applied to in-depth profile control, was synthesized by combining FA-BGPP network—a dynamic covalent cross-linking network based on Diels-Alder reaction with PAHH network—a temperature-resistant and high-strength polymer network. Due to retro Diels-Alder reaction, FA-BGPP network can decompose into fragments at high temperature and exude to gel surface to form a lubricating layer, thus endowing PAFB with self-lubricating ability. Meanwhile, PAHH network with good temperature resistance acts as protective frame to make PAFB gel being of high strength at high temperature. From oil displacement experiments results at 120 °C, compared with PAHH, the plugging rate, differential pressure at subsequent water flooding stage, fractional flow in low permeability sandpack and oil recovery of PAFB-0.7 gel were increased by 41.6%, 57.3%, 60% and 44.6% respectively, up to 83.1%, 118 KPa, 80% and 75.6%, showing its good performance for in-depth profile control and enhanced oil recovery.

Liquid Thermo-Responsive Smart Window Derived from Hydrogel

Summary Buildings account for 40% of global energy consumption, while windows are the least energy-efficient part of buildings. Conventional smart windows only regulate solar transmission. For the first time, we developed high thermal energy storage thermo-responsive smart window (HTEST smart window) by trapping the hydrogel-derived liquid within glasses. The excellent thermo-responsive optical property (90% of luminous transmittance and 68.1% solar modulation) together with outstanding specific heat capacity of liquid gives the HTEST smart window excellent energy conservation performance. Simulations suggested that HTEST window can cut off 44.6% heating, ventilation, and air-conditioning (HVAC) energy consumption compared with the normal glass in Singapore. In outdoor demonstrations, the HTEST smart window showed promising energy-saving performance in summer daytime. Compared with conventional energy-saving glasses, which need expensive equipment, the thermo-responsive liquid-trapped structure offers a disruptive strategy of easy fabrication, good uniformity, and scalability, together with soundproof functionality that opens an avenue for energy-saving buildings and greenhouses.