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Porous silicon 1D photonic crystals, namely rugate filters, are covered with a loosely packed hexagonally ordered array of stimuli‐responsive hydrogel microgels, and the optical properties of the resulting hybrid sensor are thoroughly investigated. For this purpose, both rugate filters with and without hydrogel microgel on top are immersed in ethanol/water mixtures possessing different compositions and NaCl solutions. Reflectance spectra of all samples are taken and analyzed concerning the spectral positions and reflectance intensity of the strong peak related to the photonic crystal rugate peak as well as the side bands resulting from Fabry–Pérot interference at the interfaces bordering the porous silicon. For the latter analysis, a Fourier transform is applied to the side bands for calculating the effective optical thickness (EOT). Thereby it can be shown that the spectral position of both the rugate peak and the EOT peak is best suited for monitoring refractive index changes in the immersion medium whereas the swelling and collapse of the stimuli‐responsive hydrogel microgel can be only detected by variations in the amplitude of the rugate peak and the EOT peak. These results are confirmed by simulations using a simple geometrical model and shall serve as guide for developing tailor‐made optical sensors. [ABSTRACT FROM AUTHOR]

A visible light- and reactive oxygen species (ROS)-responsive pressure/strain sensor based on carbon dot (CD)-loaded conductive hydrogel was developed for detecting high-fat diet (HFD) and preventing the risk of non-alcoholic fatty liver disease. The designed nanoparticle consisted of a diselenide polymer dot (dsPD) loaded with a visible light-responsive CD to form dsPD@CD (DSCD). The influence of visible light irradiation and ROS on DSCD facilitated the electron transport, enhancing the conductivity of DSCD-embedded hydrogel (DSCD hydrogel) from 1.3 to 35.9 mS/m. Alternatively, the tensile modulus of the DSCD hydrogel enhanced to 223 % after light-induced ROS treatment, which simultaneously impacted the capacitive response (120 %). The hydrogel implantation into inguinal white adipose tissue of HFD mice showed 82 % higher conductivity and 83 % enhanced pressure sensing response to HFD-generated high ROS levels compared with the normal diet-fed mice. Additionally, the ROS scavenging activity of DSCD hydrogel was confirmed by the downregulation of ROS-responsive genes, such as Sod2, Nrf2 , and catalase (Cat) in murine primary hepatocytes isolated from fatty liver-induced mice. In addition, in vivo animal studies also confirmed the suppression of hepatic lipogenesis, as shown by decreased Pparγ and Fasn expression and hypertrophy of adipocytes in HFD mice. The distinguishable real-time wireless resistance response observed with pressure sensing indicates the potential application of the device for monitoring the risk of non-alcoholic fatty liver disease. A visible-light-induced ROS-responsive carbon dot-loaded conductive hydrogel was developed for the detection of HFD-induced alterations in ROS levels by evaluating the conductivity and electrochemical responses with applied pressure/strain. The implanted hydrogel facilitates the recovery of the inflated adipocytes induced by NAFLD, which reduces fat accumulation in the liver, preventing the risk of NAFLD. Real-time detection based on the resistance response during local compression of the hydrogel is possibly performed utilizing a wireless sensing device, demonstrating the ease of NAFLD monitoring. [Display omitted] [ABSTRACT FROM AUTHOR]

The potentials held by stimuli-responsive polymers in wound dressing have led to the present research in formulating a hydrogel base formulation with polymers having pH and thermo-sensitivity. Thus, hyaluronic acid (pH-sensitive polymer), and Pluronic F-127 (thermo-sensitive polymer) with hydroxypropyl methylcellulose (mucoadhesive polymer) were incorporated to obtain an in situ hydrogel containing gentamicin and naringenin (NAR). The optimization of the stimuli-responsive formulation was performed by the Box–Behnken statistical design to acquire variable parameters that influence the gelling temperature and viscosity. Thermo-gravimetric analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy were performed to confirm the suitability of incorporating the selected polymers with drugs. The optimized formulations (blank and drug-loaded) were found to possess satisfactory characteristics of gelling temperatures (30–33°C), viscosities (174 ± 3 to 184 ± 4 cP), and mucoadhesive properties (0.29 ± 0.01 to 0.31 ± 0.01 N) with a spray diameter of 16.8 ± 1.4 to 18.9 ± 1.2 cm2 to facilitate the application at the wound environment. The in vitro drug release study depicted a sustained release profile over a time frame of 8 h with a cumulative release of 56.18 ± 4.59% NAR. The drug-containing in situ hydrogels showed superior potency by producing a larger zone of inhibition (2.03 ± 0.12 cm). Furthermore, a cytotoxicity study of the developed formulations in HaCaT cells revealed no toxicity of the drug-loaded formulations when compared to the blank hydrogel. These findings indicate the potential of the in situ hydrogel as an effective wound dressing for chronic wounds; however, additional investigation is needed for further implementation.

Abstract Porous silicon 1D photonic crystals, namely rugate filters, are covered with a loosely packed hexagonally ordered array of stimuli‐responsive hydrogel microgels, and the optical properties of the resulting hybrid sensor are thoroughly investigated. For this purpose, both rugate filters with and without hydrogel microgel on top are immersed in ethanol/water mixtures possessing different compositions and NaCl solutions. Reflectance spectra of all samples are taken and analyzed concerning the spectral positions and reflectance intensity of the strong peak related to the photonic crystal rugate peak as well as the side bands resulting from Fabry–Pérot interference at the interfaces bordering the porous silicon. For the latter analysis, a Fourier transform is applied to the side bands for calculating the effective optical thickness (EOT). Thereby it can be shown that the spectral position of both the rugate peak and the EOT peak is best suited for monitoring refractive index changes in the immersion medium whereas the swelling and collapse of the stimuli‐responsive hydrogel microgel can be only detected by variations in the amplitude of the rugate peak and the EOT peak. These results are confirmed by simulations using a simple geometrical model and shall serve as guide for developing tailor‐made optical sensors.

Stimuli‐responsive hydrogels are intriguing biomimetic materials. Previous efforts to develop mechano‐responsive hydrogels have mostly relied on chemical modifications of the hydrogel structures. Here, we present a simple, generalizable strategy that confers mechano‐responsive behavior on hydrogels. Our approach involves embedding hybrid vesicles, composed of phospholipids and amphiphilic block copolymers, within the hydrogel matrix to act as signal transducers. Under mechanical stress, these vesicles undergo deformation and rupture, releasing encapsulated compounds that can control the hydrogel network. To demonstrate this concept, we embedded vesicles containing ethylene glycol tetraacetic acid (EGTA), a calcium chelator, into a calcium‐crosslinked alginate hydrogel. When compressed, the released EGTA sequesters calcium ions and degrades the hydrogel. This study provides a novel method for engineering mechano‐responsive hydrogels that may be useful in various biomedical applications. [ABSTRACT FROM AUTHOR]

Diabetes is one of the most common chronic diseases that contribute significantly to global mortality. Effective glucose-sensing platforms might allow for an improved monitoring of disease progression, leading to a better health management. Optical sensors based on smart materials, particularly those that respond to external stimuli, have recently paved the way for diabetes management. Such sensors surpass traditional ones due to their unique label-free, quantitative, continuous measurement capabilities and reusability, and can be paired with equipment-free text or picture display. In the current review, we have thoroughly explored the efficient interaction of the target analyte (glucose) with these smart sensing materials by varying a variety of optical parameters such as wavelength, diffracted and diffused light pattern, signal strength, and refractive index. We also highlight the obstacles and opportunities of using smart materials in biosensing research.

[Display omitted] Understanding the factors that control the formation of (supra)molecular hydrogels permits a rational tuning of their properties and represents a primary challenge for developing smart biocompatible soft materials. Hydrogel formation by molecular amphiphilic anions at millimolar concentrations is counterintuitive, considering the solubility of these species in water. Here we report hydrogel formation by a simple anionic molecular amphiphile and a rationale for the fibrillisation process observed. The studied molecule, DodValSuc, consists of a 12C alkyl chain, an l -valine unit and a terminal succinic acid moiety. Hydrogelation depends to a large degree on the nature and concentration of the alkaline cations present in the medium (Li+, Na+ or K+). As a result, gelation efficiency and properties like thermal stability or rheology are highly tunable using the alkaline cation present or its concentration as variables. A detailed study is reported, which includes the determination of minimum gelation concentration (MGC) by tabletop rheology, critical micelle concentration (CMC) using pyrene as a fluorescent probe, thermal stability (solubility) by 1H NMR, the morphology of the fibres by transmission electron microscopy (TEM), crystallinity by X-ray diffraction (XRD) and gel strength by oscillatory rheology. Additionally, dynamic light scattering (DLS) was used to evaluate the size of the micelles and permitted monitoring of the fibrillisation process. Altogether, the results are consistent with the formation of micelles that experience head crystallisation and subsequent aggregation into crystalline fibres. The alkaline cations play a crucial role in providing the cement that glues together the gelator molecules, making their concentration a critical parameter for gelation efficiency and properties. Furthermore, the gelation-promoting effects are inversely correlated with the size of the cations so that the highest thermal stability and rheological strength were found for the hydrogels formed in the presence of Li+. [ABSTRACT FROM AUTHOR]

Diabetes is one of the most common chronic diseases that contribute significantly to global mortality. Effective glucose-sensing platforms might allow for an improved monitoring of disease progression, leading to a better health management. Optical sensors based on smart materials, particularly those that respond to external stimuli, have recently paved the way for diabetes management. Such sensors surpass traditional ones due to their unique label-free, quantitative, continuous measurement capabilities and reusability, and can be paired with equipmentfree text or picture display. In the current review, we have thoroughly explored the efficient interaction of the target analyte (glucose) with these smart sensing materials by varying a variety of optical parameters such as wavelength, diffracted and diffused light pattern, signal strength, and refractive index. We also highlight the obstacles and opportunities of using smart materials in biosensing research. [ABSTRACT FROM AUTHOR]

Achieving adequate cell densities remains a major challenge in establishing economic biotechnological and biomedical processes. A possible remedy is microcarrier-based cultivation in stirred-tank bioreactors (STBR), which offers a high surface-to-volume ratio, appropriate process control, and scalability. However, despite their potential, commercial microcarriers are currently limited to material systems featuring unnatural mechanical properties and low adaptability. Because matrix stiffness and ligand presentation impact phenotypical attributes, differentiation potential, and genetic stability, biotechnological processes can significantly benefit from microcarrier systems tailorable toward cell-type specific requirements. This study introduces hydrogel particles co-polymerized from poly(N-isopropylacrylamide) (PNIPAM) and acrylic acid (AAc) as a platform technology for cell expansion. The resulting microcarriers exhibit an adjustable extracellular matrix-like softness, an adaptable gel charge, and functional carboxyl groups, allowing electrostatic and covalent coupling of cell adhesive and cell fate-modulating proteins. These features enable the attachment and growth of L929 mouse fibroblast cells in static microtiter plates and dynamic STBR cultivations while also providing vital growth factors, such as interleukin-3, to myeloblast-like 32D cells over 20 days of cultivation. The study explores the effects of different educt compositions on cell-particle interactions and reveals that PNIPAM-co-AAc microcarriers can provide both covalently coupled and diffusively released cytokine to adjacent cells., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Structure changes mediated by anisotropic volume changes of stimuli‐responsive hydrogels are useful for many research fields, yet relatively simple structured objects are mostly used due to limitation in fabrication methods. To fabricate complex 3 dimensional (3D) structures that undergo structure changes in response to external stimuli, jammed microgel‐based inks containing precursors of stimuli‐responsive hydrogels are developed for extrusion‐based 3D printing. Specifically, the jammed microgel‐based inks are prepared by absorbing precursors of poly(acrylic acid) or poly(N‐isopropylacrylamide) in poly(acrylamide) (PAAm) microgels, and jamming them. The inks exhibit shear‐thinning and self‐healing properties that allow extrusion of the inks through a nozzle and rapid stabilization after printing. Stimuli‐mediated volume changes are observed for the extruded structures when they are post‐crosslinked by UV light to form interpenetrating networks of PAAm microgels and stimuli‐responsive hydrogels. Using this method, a dumbbell‐shaped object that can transform to a biconvex shape, and a gripper that can grasp and lift an object in response to stimuli are 3D‐printed. The jammed microgel‐based 3D printing strategy is a versatile method useful for variety of applications as diverse types of monomers absorbable in the microgels can be used to fabricate complex 3D objects transformable by external stimuli. [ABSTRACT FROM AUTHOR]

With the development of bionics and nanophotonics, hydrogel microactuators capable of responding to external stimuli to produce controllable deformations have attracted a great deal of interest. These microactuators hold significant promise in areas such as bionic devices, soft robotics, and precision sensors. It is not a trivial task to make such small devices as well as to make them work in a controlled manner. Here, inspired by the intelligent response of flytrap, a smart hydrogel microactuator based on a bionic asymmetric structure is demonstrated. The designed asymmetric microstructure is fabricated by femtosecond laser direct writing with deformation time of 1.2 s and recovery time of 0.3 s. The grasping and releasing behavior of the microactuator for micro‐objects can be realized and tuned by using pH‐triggered shape changes, demonstrating its potential for applications, such as flexible robotics, smart sensors, and microscopic manipulation. [ABSTRACT FROM AUTHOR]

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an ad hoc synthesized amphiphilic poly(ether urethane) (CHP407) exposing a significant amount of –COOH groups (8.8 ± 0.9 nmol/gpolymer). The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature (12.1 °C vs. 14.6 °C, respectively) and gelation rate than CHP407 hydrogel, as rheologically assessed. Nanoscale hydrogel characterization by Low Field NMR (LF-NMR) spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels, as further proved by Dynamic Light Scattering analyses. In addition, P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer (pH 8) (e.g., pHchange_5min = 3.76 and 1.32, respectively). Moreover, LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing –COOH groups. Lastly, the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen: delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH, suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

In nature, some insects can rapidly propel by using the Marangoni effect without employing the oscillatory movements of legs. Inspired by nature's Marangoni‐propulsion principles, various Marangoni‐propulsion untethered micro‐robots are achieved to propel with small energy storage. For practical use of Marangoni‐propulsion micro‐robots, it is required to have the intelligence to detect the external environment. However, previous Marangoni‐propulsion micro‐robots integrated with wireless micro‐scale sensors that can sense the external environment and transmit the obtained information are not achieved. Herein, Marangoni propulsion micro‐robots integrated with a wireless photonic gel sensor for exploring the aquatic environment and transmitting the environmental information are proposed. The proposed micro‐robots can propel at the water–air interface by the Marangoni effect. The integrated photonic gel sensor can sense the external stimuli and transmit the information by the color change. In this research, the responsivity of the micro‐robots is evaluated by the propulsion velocity and the response time of the photonic gel. It is shown that the propulsion velocity is changed by the outlet area. The response time decreased as the diameter of the photonic gel decreased. Finally, it is demonstrated that the photonic gel sensor can dynamically sense the external stimuli while the micro‐robots propel. [ABSTRACT FROM AUTHOR]

In nature, some insects can rapidly propel by using the Marangoni effect without employing the oscillatory movements of legs. Inspired by nature's Marangoni‐propulsion principles, various Marangoni‐propulsion untethered micro‐robots are achieved to propel with small energy storage. For practical use of Marangoni‐propulsion micro‐robots, it is required to have the intelligence to detect the external environment. However, previous Marangoni‐propulsion micro‐robots integrated with wireless micro‐scale sensors that can sense the external environment and transmit the obtained information are not achieved. Herein, Marangoni propulsion micro‐robots integrated with a wireless photonic gel sensor for exploring the aquatic environment and transmitting the environmental information are proposed. The proposed micro‐robots can propel at the water–air interface by the Marangoni effect. The integrated photonic gel sensor can sense the external stimuli and transmit the information by the color change. In this research, the responsivity of the micro‐robots is evaluated by the propulsion velocity and the response time of the photonic gel. It is shown that the propulsion velocity is changed by the outlet area. The response time decreased as the diameter of the photonic gel decreased. Finally, it is demonstrated that the photonic gel sensor can dynamically sense the external stimuli while the micro‐robots propel.

Stimuli-responsive hydrogels with embedded magnetic microparticles (i.e., ferrogel) can be integrated with a planar LC circuit to remotely monitor environmental changes via electromagnetic resonant frequency measurements. To investigate the sensing mechanism from the point of view of magnetic susceptibility, we conducted magnetic characterizations of ferrogel swelling/deswelling in response to stimuli (i.e., pH), an indication of the extent of physical restriction of the particles. Within 4 hours, a $2 \times 2$ mm2 ferrogel can achieve an equilibrium swelling, reaching 10.8 times of its original weight when at pH 6, compared to 2.8 times when at pH 4. The magnetic remanence of the ferrogel is 3 emu/g, revealing a thermally blocked Néel relaxation; moreover, by comparing the complex susceptibility of the ferrogel between its equilibrium swelling and complete dry, the gel is found to have a Brown characteristic frequency at 2.2 Hz. When the gel switches from pH 4 to pH 6, the magnetic susceptibility of the gel increases from $2.99\,\,\times10$ -7 emu/oe to $3.27\,\,\times10$ -7 emu/oe, achieving a sensitivity of $3.5\,\,\times10$ -9 (emu/oe)/pH per swelling ratio between pH 4 and pH 6. These data verified that the ferrogel works as a magnetic core to tune the magnetic capacity (i.e., inductance) and thus resonance frequency of its incorporated sensing system through its volumetric response to external chemical stimuli. [ABSTRACT FROM AUTHOR]

Abstract Nucleic acid‐based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new‐generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid‐based hydrogels. Also, recent advances in the design of multifunctional and stimuli‐responsive nucleic acid‐based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined.

Nucleic acid‐based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new‐generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid‐based hydrogels. Also, recent advances in the design of multifunctional and stimuli‐responsive nucleic acid‐based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined. [ABSTRACT FROM AUTHOR]

Drug delivery vectors based on amphiphiles have important features such as versatile physicochemical properties and stimuli‐responsiveness. Amino acid‐based surfactants are especially promising amphiphiles due to their enhanced biocompatibility compared to conventional surfactants. They can self‐organize into micelles, vesicles and complex hierarchical structures, such as fibers, twisted and coiled ribbons, and tubules. In this work, we investigated the self‐assembly and drug loading properties of a family of novel anionic double‐tailed lysine‐derived surfactants, with variable degree of tail length mismatch, designated as mLys10 and 10Lysn, where m and n are the number of carbon atoms in the tails. These surfactants form tubular aggregates with assorted morphologies in water that undergo gelation due to dense entanglement, as evidenced by light and electron microscopy. Lysozyme (LZM), an enzyme with antimicrobial properties, was selected as model protein for loading. After the characterization of the interfacial properties and phase behavior of the amphiphiles, the LZM‐loading ability of the tubules was investigated, under varying experimental conditions, to assess the efficiency of the aggregates as pH‐ and temperature‐sensitive nanocarriers. Further, the toxicological profile of the surfactants per se and surfactant/LZM hydrogels was obtained, using human skin fibroblasts (BJ‐5ta cell line). Overall, the results show that the tubule‐based hydrogels exhibit very interesting properties for the transport and controlled release of molecules of therapeutic interest. [ABSTRACT FROM AUTHOR]

Hydrogels are emerging as enabling materials for a wide range of new applications for soft robots because of their flexibility. Some of the polymer chains that make up the hydrogel have a nano-scale function of swelling and contracting in response to external stimuli. In addition, because the network of polymer chains is on the nanometer order, it is possible to encapsulate various functional materials. Therefore, stimulus-responsive hydrogels and functional materials encapsulating hydrogels are also being actively studied for use as soft robot components. From a fundamentals point of view, the nano-scale functions of hydrogels, fabrication method, and integration with functional materials must be considered for each specific application. This section provides a basic understanding of hydrogels and the recent development of novel fabrication and integration of hydrogel with functional materials such as magnetic nanoparticles, Pt catalyst, graphene, photonic colloidal crystal, and living cells. [ABSTRACT FROM AUTHOR]

• Mandelic acid-triethylene tetraamine -Eu3+ forms Stimuli responsive WLE hydrogel. • Increasing Eu3+, PL intensity of MA–TETA decreases ,indicating energy transfer. • Exciting at 330 nm(0.34, 0 33) MA-TETA - Eu3+ gel emits white light, QY 11.4%. • Froster distance 1.7 Å for complex formation in hydrogel but in sol no white light. • Xerogel emit white light and WLE hydrogel has Correlated colour temperature 5148 K. Recently, there is incredible growth on optoelectronic properties of new supramolecular gels and white-light-emitting (WLE) metalo-organic gel comprised with single lanthanide metal ion having stimuli-responsive property is not yet reported. Here, we report a mandelic acid (MA)-triethylene tetraamine (TETA)-Eu-acetate conjugate (4.5:1:0.4 mol ratio), producing stimuli-sensitive WLE hydrogel exhibiting thermoreversible, thixotropic, pH-switchable, self-standing and self-healing properties. Energy minimized structure suggests complexation between MA-TETA conjugate and Eu3+ ion. Fluorescence intensity of MA–TETA conjugate decreases with increasing Eu3+ concentration indicating energy transfer from MA-TETA to Eu3+. Decay of donor fluorescence intensity follows Stern-Volmer equation and energy transfer efficiency is 42%. WLE gel has Quantum yield 11.4% and Förster distance 1.7 Å. Hydrogel and xerogel show WLE on excitation at 330 and 350 nm having CIE coordinates (0.34, 0.33) and (0.28, 0.32), respectively. WLE gel has Correlated colour temperature 5148 K, appropriate for cool day light emission and on coating over UV-LED bulb it emits bright white light. [ABSTRACT FROM AUTHOR]

Featured Application: The developed thermoresponsive injectable hydrogels might be used as cell-delivery systems, 3D matrices for cell culture study, drug screening platforms, and for regenerative medicine applications. The three-dimensional complexity of the native extracellular matrix (ECM) suggests switching from 2D to 3D culture systems for providing the cells with an architecture more similar to the physiological environment. Reproducing the three-dimensionality in vitro can guarantee beneficial effects in terms of cell growth, adhesion, proliferation, and/or their differentiation. Hydrogels have the same tailorable physico-chemical and biological characteristics as ECM materials. In this study, we propose a thermoresponsive chitosan-based hydrogel that gels thanks to the addition of organic and inorganic salt solutions (beta-glycerolphosphate and sodium hydrogen carbonate) and is suitable for cell encapsulation allowing obtaining 3D culture systems. Physico-chemical analyses showed that the hydrogel formulations jellify at physiological conditions (37 °C, pH 7.4), are stable in vitro up to three weeks, have high swelling ratios and mechanical stiffness suitable for cellular encapsulation. Moreover, preliminary biological tests underlined the pronounced biocompatibility of the system. Therefore, these chitosan-based hydrogels are proposed as valid biomaterials for cell encapsulation. [ABSTRACT FROM AUTHOR]

Focus of the present studies was to synthesize a novel pH sensitive and thermoresponsive hydrogel which may show swelling behavior suitable for drug delivery at colon part of body. For this purpose, starch was copolymerized with methyl-3-aminocrotonate through free radical polymerization. The structural and thermal characterization of wheat starch/methyl-3-aminocrotonate hydrogel was carried out by XRD, FTIR and TGA. FTIR and XRD confirmed successful formation of the gel. Thermal data were further subjected to the isoconversional method for the determination of kinetic triplet (activation energy Ea, frequency factor A and g(α) function) to predict mechanism for thermal degradation of the synthesized gel. The first step showed a complex mechanism of thermal degradation, i.e., A2 followed by A3/2. Thermodynamic parameters ΔS* and ΔG* were also calculated. Moreover, swelling investigations unveiled these gels to be pH sensitive and thermoresponsive. The swelling percentage markedly increased with increasing pH and temperature. Kinetic order of swelling, diffusion mechanism and network parameters (i.e., molecular weight between cross-links and volume faction of polymers) of the synthesized hydrogel was also determined. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive materials have the potential to enable the generation of new bioinspired devices with unique physicochemical properties and cell‐instructive ability. Enhancing biocompatibility while simplifying the production methodologies, as well as enabling the creation of complex constructs, i.e., via 3D (bio)printing technologies, remains key challenge in the field. Here, a novel method is presented to biofabricate cellularized anisotropic hybrid hydrogel through a mild and biocompatible process driven by multiple external stimuli: magnetic field, temperature, and light. A low‐intensity magnetic field is used to align mosaic iron oxide nanoparticles (IOPs) into filaments with tunable size within a gelatin methacryloyl matrix. Cells seeded on top or embedded within the hydrogel align to the same axes of the IOPs filaments. Furthermore, in 3D, C2C12 skeletal myoblasts differentiate toward myotubes even in the absence of differentiation media. 3D printing of the nanocomposite hydrogel is achieved and creation of complex heterogeneous structures that respond to magnetic field is demonstrated. By combining the advanced, stimuli‐responsive hydrogel with the architectural control provided by bioprinting technologies, 3D constructs can also be created that, although inspired by nature, express functionalities beyond those of native tissue, which have important application in soft robotics, bioactuators, and bionic devices.A novel method is presented to biofabricate anisotropic nanocomposite hydrogels through a mild and biocompatible process driven by multiple external stimuli: magnetic field, temperature, and light. The functionality of this stimuli‐responsive hydrogel is studied creating i) 3D cell‐instructive platforms for in vitro morphogenesis, and ii) a 3D printable magnetoresponsive ink for fabricating small‐scale bioinspired soft robots. [ABSTRACT FROM AUTHOR]

Human tissues are sophisticated ensembles of various distinct cell types encapsulated in the biomechanical cues of the extracellular matrix. It has been known matrix stiffness plays a pivot role in cellular events and tissue‐scale biological processes. Thus, materials that can mimic mechanical environments of tissues in vitro and possess wide, physiologically relevant elasticity are highly desirable. Hydrogels provide a good cell platform to mimic native cellular environment. However, the limited stiffness tunability, and hinders the efforts to reproduce the biomechanical microenvironment of many in vivo progresses. These problems have been addressed by the recently emerged great quantity of exquisitely designed smart hydrogels. Smart hydrogels that respond sensitively to external stimuli are good choices due to the convenience in regulating their mechanical properties. In this review, we summarize the latest progress in the development of stimuli‐responsive hydrogels as a cell carrier (platform for cell culture) which spans a wide range of stiffness. Different kinds of smart hydrogels corresponding to various stimuli, including pH, temperature, light, metal ions, and forces, are introduced and their stiffness modulation through physicochemical procedures are reported. [ABSTRACT FROM AUTHOR]

[Display omitted] • A CoA-SH-responsive electronic hydrogel sensor that could treat osteoarthritis. • Mechanical and pressure sensitivity alterations upon reaction with CoA-SH. • Controlled electrical conductivity based on the accumulation of CoA-SH in a DMM-induced Nudt7-/- mice. • Therapeutic performance by preventing the degradation of cartilage in OA mice model after treated with hydrogel. A coenzyme A (CoA-SH)-responsive electronic hydrogel sensor that can relieve osteoarthritis based on carbonized polydopamine-integrated disulfide bonds-contained polymer dots (cPDA@PDA hydrogel) is conceived in this study. The cleavage of disulfide bonds occurred due to the accumulation of CoA-SH, controlling the release of carbonized polydopamine (cPDA) from the integrated polymer dots (PD). The hydrogel mechanical properties are altered, increasing the maximum stretching from 199.7 % to 352.9 % after 12 h and the shift in the surface morphology. The exposure to CoA-SH controls the release of the cPDA, decreasing the electronic resistivity from 147.1 kΩ to 56.99 kΩ after 12 h. In vitro analysis using the articular chondrocytes of wild type (WT), Nudt7-/-, and Acot12-/- shows a sensitivity toward CoA-SH, which is depicted by the decrease in electronic resistance after treatment. In vivo analysis shows a resistance of 131.1 kΩ for the Nudt7-/- mice, which is lower than the resistance of the NUDT7-restored mice (225.1 kΩ). Additionally, cartilage degradation could be prevented for mice-treated PD-containing hydrogel, showing tibia thickness of 111.5 μm compared to that without PD hydrogel (74.84 μm). This result indicates that the cPDA@PD hydrogel can diminish the accumulation of CoA-SH and facilitate the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer–Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.

The three-dimensional complexity of the native extracellular matrix (ECM) suggests switching from 2D to 3D culture systems for providing the cells with an architecture more similar to the physiological environment. Reproducing the three-dimensionality in vitro can guarantee beneficial effects in terms of cell growth, adhesion, proliferation, and/or their differentiation. Hydrogels have the same tailorable physico-chemical and biological characteristics as ECM materials. In this study, we propose a thermoresponsive chitosan-based hydrogel that gels thanks to the addition of organic and inorganic salt solutions (beta-glycerolphosphate and sodium hydrogen carbonate) and is suitable for cell encapsulation allowing obtaining 3D culture systems. Physico-chemical analyses showed that the hydrogel formulations jellify at physiological conditions (37 °C, pH 7.4), are stable in vitro up to three weeks, have high swelling ratios and mechanical stiffness suitable for cellular encapsulation. Moreover, preliminary biological tests underlined the pronounced biocompatibility of the system. Therefore, these chitosan-based hydrogels are proposed as valid biomaterials for cell encapsulation.

This study describes a novel microfluidics-based method for compressive/expanding actuation of stimuli-responsive hydrogel microsprings with large deformations. A continuous flow of mixed alginate and poly( N -isopropylacrylamide- co -acrylic acid) pre-gel solution can spontaneously form a hydrogel microspring with a wide range of gradient pitches via buoyancy force. This technique enables fabrication of hydrogel microsprings using only simple capillaries and syringe pumps. The resulting microsprings can be patterned via laminar flow inside the capillary, which can contribute to large deformation. Single-layered hydrogel microsprings shrunk isotropically while maintaining the shape of the spring. Compressing stimuli-responsive microsprings can be done by patterning the shrinking part of the spring. Here, the degree of compression in the double-layered spring depends on the initial pitch. Furthermore, large axial expansion of microsprings can be achieved by shrinking part of a microspring. Our large compression/expansion stimuli-responsive hydrogel microsprings have immense potential to be applied in various microengineering products including soft actuators, chemical sensors, and medical applications. [ABSTRACT FROM AUTHOR]

This work describes the synthesis and characterization of pH-responsive hydrogels based on alginate for protein delivery. Synthesis approach shown here has included the modification of sodium alginate to convert it into a covalently crosslinkable polysaccharide and the subsequent radical polymerization reaction with sodium acrylate and N -vinylpyrrolidone for hydrogelation. To evaluate the applicability of the obtained hydrogels as an oral protein delivery system, we studied the cytotoxicity, the drug release profile (using BSA as a protein model), and the swelling performance in the basic and acidic environments. The hydrogels showed a pH-dependent swelling profile with higher value at pH 7.4. The protein release mechanism was demonstrated to be dependent on pH and composition. The proposed materials were shown to be compatible with living cells, indicating great pharmacological potential. These results show that the hydrogels are ideally suited for use as an oral drug delivery device. [ABSTRACT FROM AUTHOR]

We propose a method to print four-dimensional (4D) stimuli-responsive hydrogel structures with internal gaps. Our 4D structures are fabricated by printing an N-isopropylacrylamide-based stimuli-responsive pre-gel solution (NIPAM-based ink) and an acrylamide-based non-responsive pre-gel solution (AAM-based ink) in a supporting viscous liquid (carboxymethyl cellulose solution) and by polymerizing the printed structures using ultraviolet (UV) light irradiation. First, the printed ink position and width were investigated by varying various parameters. The position of the printed ink changed according to physical characteristics of the ink and supporting liquid and printing conditions including the flow rates of the ink and the nozzle diameter, position, and speed. The width of the printed ink was mainly influenced by the ink flow rate and the nozzle speed. Next, we confirmed the polymerization of the printed ink in the supporting viscous liquid, as well as its responsivity to thermal stimulation. The degree of polymerization became smaller, as the interval time was longer after printing. The polymerized ink shrunk or swelled repeatedly according to thermal stimulation. In addition, printing multi-hydrogels was demonstrated by using a nozzle attached to a Y shape connector, and the responsivity of the multi-hydrogels to thermal-stimulation was investigated. The pattern of the multi-hydrogels structure and its responsivity to thermal-stimulation were controlled by the flow ratio of the inks. Finally, various 4D structures including a rounded pattern, a spiral shape pattern, a cross point, and a multi-hydrogel pattern were fabricated, and their deformations in response to the stimuli were demonstrated.

Urea is used in a wide variety of industrial applications such as the production of fertilizers. Furthermore, urea as a metabolic product is an important indicator in biomedical diagnostics. For these applications, reliable urea sensors are essential. In this work, we present a novel hydrogel-based biosensor for the detection of urea. The hydrolysis of urea by the enzyme urease leads to an alkaline pH change, which is detected with a pH-sensitive poly(acrylic acid-co-dimethylaminoethyl methacrylate) hydrogel. For this purpose, the enzyme is physically entrapped during polymerization. This enzyme-hydrogel system shows a large sensitivity in the range from 1 mmol/L up to 20 mmol/L urea with a high long-term stability over at least eight weeks. Furthermore, this urea-sensitive hydrogel is highly selective to urea in comparison to similar species like thiourea or N-methylurea. For sensory applications, the swelling pressure of this hydrogel system is transformed via a piezoresistive pressure sensor into a measurable output voltage. In this way, the basic principle of hydrogel-based piezoresistive urea biosensors was demonstrated.

A fast and reliable determination of the ethanol concentration is essential in the analysis of alcoholic beverages. However, different factors like pH value or salt concentration can influence the ethanol measurement. Furthermore, analytical figures of merit for the alcohol sensor, such as limit of detection, sensitivity and measurement uncertainty, are necessary for the application. In this paper, a detailed sensor characterization of a novel sensor based on ethanol-sensitive poly acrylamide hydrogels will be presented. The resulting swelling pressure of the hydrogel was transformed via a piezoresistive pressure sensor into a measurable output voltage. These kinds of sensors can be used over a large measuring range, up to 50 vol% ethanol and more, with a high sensitivity. In the range from pH 7.4 to 4, the pH value had no influence on the sensor signal. Higher salt concentrations can slightly influence the measurement. The detection limit amounts to 0.06–0.65 vol% ethanol. The concentration of a vodka sample was determined with a sufficient measuring uncertainty.

Ammonia is an essential key compound in the chemical industry. However, excessively high ammonia concentrations can be harmful to the environment. Sensors for the detection of ammonia are therefore particularly important for environmental analysis. In this article, a novel hydrogel-based piezoresistive ammonia sensor is presented. In aqueous solution, ammonia reacts as a base. This alkaline pH change can be detected with stimuli-sensitive hydrogels. For such an application, highly sensitive hydrogels in the alkaline range with sufficient mechanical stability for the sensor application has to be developed. These conditions are fulfilled by the presented hydrogel system based on acrylic acid (AAc) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The hydrogel composition has a significant influence on the swelling behavior of the gel. Furthermore, the hydrogel swelling in ammonia solutions was tested and a detection limit in the range of 1 mmol/L ammonia depending on the buffer solution was determined. Ammonia-sensitive hydrogels can be used multiple times due to the repeatable swelling of the gel over several swelling cycles. To generate a measurable output voltage, the swelling pressure of ammonia-sensitive hydrogels were detected by using piezoresistive pressure sensors. All results of the free hydrogel swelling were verified in the sensor application. This low-cost ammonia sensor with a high sensitivity could be interesting for industrial chemical and biotechnological applications.

We developed an interesting route for preparing a poly (acrylamide- co -acrylic acid) (P(AAm- co -AA)) hydrogel microsphere with a coating of Au nanospheres (hydrogel microsphere @ Au nanospheres) through self-assembly based on electrostatic interaction. The fabricated composites could be used as highly sensitive enhanced Raman scattering substrates. The nanogaps between adjacent Au nanospheres were dynamically tuned by volume changes in the hydrogel microspheres in the semiwet state under different pH conditions. At pH 6, the hydrogel microsphere @ Au nanospheres demonstrated highly sensitive SERS with an enhancement factor of 10 9 . The product could detect very low concentrations of analytes up to 10 −12 M 4-aminothiophenol (4-ATP) molecules. This paper proposes a new method for detecting trace amounts of environmental organic pollutants by dynamically tuning the SERS enhancement in the semiwet testing state. [ABSTRACT FROM AUTHOR]

Poly(ethylene glycol) (PEG 1500) is functionalized using itaconic acid by melt esterification reaction to obtain a bi-functional co-monomer crosslinker, Poly(ethylene glycol) di-itaconate. The resulting product has been copolymerized with acrylamide in presence of methylene bis-acrylamide as crosslinker (in varying proportions) so as to prepare hydrogel which is mostly recommended for dye removal from textile effluents. FTIR-ATR, Solid state 13-C NMR and WAXS techniques are used to ensure grafting of the PEG diitaconate on the polyacrylamide backbone. The intermediate products are also characterized using FTIR and 1 H NMR spectroscopy. This study reveals that a significant improvement in gel characteristics particularly in respect of swelling properties may be achieved with the hydrogel having only ester type crosslinks. However this is attained at the cost of yield stress. The ester based gel shows better storage modulus, dye sorption ability and the anti-fungal properties in relation to semi-IPN type gels. [ABSTRACT FROM AUTHOR]

Due to the particularity of the tendon-to-bone interface, the integration of tendon graft and bone after anterior cruciate ligament (ACL) reconstruction is the key to the success of the surgery. This reconstruction requires early on-demand angiogenesis and osteogenesis to promote early and rapid healing of the tendon-to-bone interface. Here, a hypoxic-mimetic 3D porous hydrogel was prepared with a multi-responsive hybrid interpenetrating network to the tendon-to-bone interfacial microenvironment under a highly hypoxic, acidic, reactive oxygen species (ROS), and related enzyme-enriched state. The hypoxia agent DFO can be effectively control-released adaptive to the stimulation of tendon-to-bone interfacial microenvironment, to upregulate HIF-1α, promote the expression of vascular endothelial growth factor, bone morphogenetic protein 2 and runt-related transcription factor 2, thereby promoting rapid early angiogenesis and bone formation on demand. At the same time, it can effectively resist oxidative stress, reduce ROS and the inflammatory response, promote better integration of the tendon-to-bone interface. Furthermore, in vivo experiments combining micro-CT, histological and biomechanical analysis also showed effective promotion of early and rapid tendon-to-bone healing. In conclusion, our study may provide a new therapeutic strategy for the integration of the tendon-to-bone interface. To promote early and rapid healing of the tendon-bone interface by on-demand angiogenesis and osteogenesis, a novel hypoxic-mimetic 3D porous interpenetrating network hydrogel was prepared with controllable release of hypoxia agent DFO multi-responsive to the stimulation of tendon-bone interfacial microenvironment. [Display omitted] • A novel stimuli-responsive hypoxia-mimetic hydrogel was developed for tendon-to-bone healing. • The fabricated hybrid interpenetrating network is multi-responsive to the highly hypoxic, acidic, ROS, and related enzyme-enriched microenvironment. • The DFO can be controllable released adaptive to the tendon-bone interfacial microenvironment, thereby promoting on demandangiogenesis and bone formation. • In vivo results from micro-CT, histological and biomechanical analysis showed effective promotion of early and rapid healing of ACL reconstruction. [ABSTRACT FROM AUTHOR]

This article describes an ammonia-responsive hydrogel based on acrylic acid (AAc) and 2-(dimethylamino)ethyl methacrylate (DMAEMA). The influence of the hydrogel composition on swelling behavior in the alkaline range was shown. Furthermore, the hydrogel swelling in ammonia solutions was tested and a detection limit in the range of 1 mmol/L ammonia in dependence of the buffer solution was determined.

Stimuli-responsive hydrogels are materials with great potential for development of active functionalities in fluidics and micro-fluidics. Based on the current state of research on pH sensors, hydrogel sensors are described qualitatively and quantitatively for the first time. The review introduces the physical background of the special properties of stimuli-responsive hydrogels. Following, transducers are described which are able to convert the non-electrical changes of the physical properties of stimuli-responsive hydrogels into an electrical signal. Finally, the specific sensor properties, design rules and general conditions for sensor applications are discussed.

The inclusion of super paramagnetic iron oxide (Fe3O4) nanoparticles in stimuli-responsive hydrogel is expected to enhance the application potential for cellular therapy in cell labeling, separation and purification, protein immobilization, contrasting enhancement in magnetic resonance imaging (MRI), localized therapeutic hyperthermia, biosensors etc. in biomedical field. In this investigation two different magnetic and stimuli-responsive composite hydrogel particles with variable surface property were prepared by simply blending Fe3O4/SiO2 nanocomposite particles with stimuli-responsive hydrogel particles. Of the hydrogel particles prepared by free-radical precipitation polymerization poly(styrene-N-isopropylacrylamide-methyl methacrylate-polyethylene glycol methacrylate) or P(S-NIPAM-MMA-PEGMA) was temperature-sensitive and poly(S-NIPAM-methacrylic acid-PEGMA) or P(S-NIPAM-MAA-PEGMA) was both temperature- and pH-responsive. The morphological structure, size distributions and volume phase transitions of magnetic and stimuli-responsive composite hydrogel particles were analyzed. Temperature-responsive absorptions of biomolecules were observed on both magnetic and stimuli-responsive Fe3O4/SiO2/P(S-NIPAM-MMA-PEGMA) and Fe3O4/SiO2/P(S-NIPAM-MAA-PEGMA) composite hydrogel particles and separation of particles from the dispersion media could be achieved by applying magnetic field without time consuming centrifugation or decantation method. [ABSTRACT FROM AUTHOR]

The hemicellulose isolated from the spent liquor of a viscose process was successfully utilized to prepare hydrogels by the graft copolymerization of acrylic acid (AA) with hemicellulose. The hemicellulose and prepared hydrogel were characterized by Fourier-transform infrared (FT-IR), scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance ( 13 C NMR). Under the optimum preparation conditions, the highest compressive strength and strain at break of the resultant hydrogel were 105.1 ± 12.9 kPa and 34.8%, respectively. Furthermore, the maximum equilibrium swelling degree of prepared hydrogel was 192. Also, the hydrogel could rapidly respond to pH, salt and ethanol. Taken together, the prepared hydrogels had great mechanical and multi-responsive properties. Thus, the prepared hydrogels had a great potential application in drug release, water treatment and cell immobilization. In addition, the utilization of alkaline extracted hemicellulose from the viscose fiber factory has huge market potential and economic benefits. [ABSTRACT FROM AUTHOR]

Stimuli-responsive hydrogels have attracted much attention over the past decade for potential bioengineering applications such as wound dressing and drug delivery. In this work, a pH and temperature dual-responsive microgel-embedded hydrogel has been fabricated by incorporating poly( N -isopropylacrylamide- co -acrylic acid) (PNIPAAm- co -AAc) based microgel particles into polyacrylamide (PAAm)/chitosan (CS) semi-interpenetrating polymer network (semi-IPN), denoted as microgel@PAM/CS. The resultant hydrogel possesses excellent mechanical properties including stretchability, compressibility, and elasticity. In addition, the microgel@PAM/CS hydrogels can tightly adhere to the surfaces of a variety of tissues such as porcine skin, kidney, intestine, liver, and heart. Moreover, it shows controlled dual-drug release profile of both bovine serum albumin (BSA) (as a model protein) and sulfamethoxazole (SMZ), an antibiotic. Excellent antimicrobial properties are obtained for SMZ-loaded microgel@PAM/CS hydrogels. Compared with traditional drug administration methods such as by mouth, injection, and inhalation, the microgel@PAM/CS hydrogels possess advantages such as higher drug loading efficiency (by more than 80%) and controllable and sustained (over 48 h) release. The microgel@PAM/CS hydrogels can significantly enhance the wound healing process. This work provides a facile approach for the fabrication of multifunctional stimuli-responsive microparticle-embedded hydrogels with semi-IPN structures, and the as-prepared microgel@PAM/CS hydrogels have great potential for applications as smart wound dressing materials in biomedical engineering.

A series of poly(ethylene glycol) diacrylate/methacrylic acid (PEGDA/MAA)-based nanogels showing multiresponsiveness toward temperature, salt concentration, and pH value were synthesized by aqueous precipitation polymerization. The effect of monomer loading amount, cross-linking degree, and cross-linker type on synthesis of hydrogels was investigated, and so were the influences of MAA content in the feed of synthesis of hydrogel, pH value, and NaCl concentration on the thermosensitivity of hydrogels. The lower critical solution temperature (LCST) of poly(PEGDA/MAA) hydrogels decreased with an increase of MAA content or NaCl concentration and a decrease of pH value. One of the resultant hydrogels (PEGDA575/MAA, 40/60 mol/mol) displayed a distinct LCST of 35 °C under a gastric liquid-like condition (pH 1.0, 150 mM NaCl). Such hydrogel showed a good potential in controlling the release of 5-fluorouracil (5-FU), an anticancer agents, under the above gastric liquid-like condition and also an intestinal liquid-like one. [ABSTRACT FROM AUTHOR]

Hydrogels are three-dimensional solid-like substances that can expand to a large extent while retaining their three-dimensional hierarchical structure. Owing to their superior qualities of high-water content, biocompatibility, degradations, and flexibility, they are attracting a lot of interest for their potential applications as topical drug administration in the form of thin films and as drug carrier vehicles. In this study, we developed a poly(ethylene glycol)-block-poly(propyleneglycol)-block-poly(ethylene glycol) (Pluronic P123)-based amphiphilic hybrid hydrogel using choline acetate ionic liquid (IL) and additional biocompatible components such as agar, glycerol, and sodium tetraborate. The resulting hybrid hydrogel loaded with iron oxide nanoparticles (NPs) was found to be a highly efficient system for drug uptake and delivery which exhibits biodegradable, stimuli-responsive, biocompatible as well as self-healing characteristics. First-principles-based density functional theory (DFT) calculations provide greater insights into the nature of intermolecular interactions participating in the formation of the hybrid hydrogel, as confirmed by infrared spectroscopy. With their enormous amenability to modification, prepared hydrogel serves as a promising delivery vehicle of diclofenac sodium (DS) drugs for anti-inflammatory drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]