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Cell-instructive polymer hydrogels are instrumental in tissue engineering for regenerative therapies. Implementing defined and selective responsiveness to external stimuli is a persisting challenge that critically restricts their functionality. Addressing this challenge, this study introduces a versatile, modular hydrogel system composed of four-arm poly(ethylene glycol)(starPEG)-peptide and glycosaminoglycan(GAG)-maleimide conjugates. The gel system features a small peptide sequence that is selectively cleaved by the coagulation factor FXa. In a cell culture environment, where active FXa is absent, the hydrogel remains stable, providing a conducive matrix for the growth of complex tissue structures or organoids. Upon the introduction of FXa, the hydrogel is designed to disintegrate rapidly, enabling the gentle release of the cultivated tissues without impairing their functionality. The efficacy of this approach is demonstrated through the ex vivo development, detachment, and transplantation of human corneal endothelial lamellae, achieving sizes relevant for clinical application in Descemet Membrane Endothelial Keratoplasty (DMEK). Furthermore, the practicality of the hydrogel system is validated in vitro using a de-endothelialized porcine cornea as a surrogate recipient. Since the FXa-cleavable peptide can be integrated into a variety of multifunctional hydrogels, it can pave the way for next-generation scaffold-free tissue engineering and organoid regenerative therapies., (© 2025 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

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.)

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. STATEMENT OF SIGNIFICANCE: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

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., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

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.

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 1 H 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 +., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

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., (© 2022 Wiley-VCH GmbH.)

Programmable materials have artificially designed physical shapes responding to external stimuli, as well as high design capability and high flexibility. Here, we propose a microfiber-shaped programmable material with an axial pattern of stimuli-responsive (SR) and nonresponsive hydrogels. The SR pre-gel solution was mixed to sodium alginate pre-gel solution for instantaneous gelation with ionic crosslinking and solidified on a nonresponsive hydrogel microfiber with a valve-controlled microfluidic system. A design of microfiber-shaped programmable material (patterned position of SR regions) could be flexibly altered by changing a coded sequence program. We confirmed that the three-dimensional (3D) coil-like structures were self-folded at the patterned SR regions responding to the thermal stimulus and that the chirality of the self-folded 3D coil-like structures depends on the condition of the stimulus to the microfiber. Finally, interaction with objects using the programmable microfiber as a soft actuator was demonstrated. Our microfiber-shaped programmable materials expand possibilities of fiber-based materials in biomimetics and soft robotics fields.

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., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

In the last years, neurological diseases have resulted in a global health issue, representing the first cause of disability worldwide. Current therapeutic approaches against neurological disorders include oral, topical, or intravenous administration of drugs and more invasive techniques such as surgery and brain implants. Unfortunately, at present, there are no fully effective treatments against neurodegenerative diseases, because they are not associated with a regeneration of the neural tissue but rather act on slowing the neurodegenerative process. The main limitation of central nervous system therapeutics is related to their delivery to the nervous system in therapeutic quantities due to the presence of the blood-brain barrier. In this regard, recently, the intranasal route has emerged as a promising administration site for central nervous system therapeutics since it provides a direct connection to the central nervous system, avoiding the passage through the blood-brain barrier, consequently increasing drug cerebral bioavailability. This review provides an overview of the nose-to-brain route: first, we summarize the anatomy of this route, focusing on the neural mechanisms responsible for the delivery of central nervous system therapeutics to the brain, and then we discuss the recent advances made on the design of intranasal drug delivery systems of central nervous system therapeutics to the brain, focusing in particular on stimuli-responsive hydrogels.

Stimuli-responsive hydrogel has been emerged as a popular tool for chemical sensing due to its unique mechanical properties. In this work, we fabricated an ascorbic acid (AA)-responsive alginate hydrogel for the visual detection of alkaline phosphatase (ALP). This alginate hydrogel (RhB@Alg/Fe 3+ ) was crosslinked with Fe 3+ , and rhodamine B (RhB) was encapsulated into the hydrogel as an indicating reagent to assistant visual detection. Because of the weak affinity of Fe 2+ to alginate, the presence of reductive AA can trigger the dissolution of RhB@Alg/Fe 3+ to give an observable red color in the sol solution. On this basis, by using ascorbic acid 2-phosphate as a substrate of ALP, which can be hydrolyzed by ALP to produce AA, the gel-sol transition process of RhB@Alg/Fe 3+ was further modulated by ALP. This finding leads to a simple visual method for ALP detection with a low detection limit of 0.37 mU/mL and an excellent selectivity over other proteins. Compared with conventional colorimetric assays, this visual sensor shows the distinct advantages of simple fabrication, cost-effectiveness and easy to implement. We believe that this study can provide a new insight into the fabrication of responsive alginate hydrogel for promising applications in chemical sensing and biomedical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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/g polymer ). 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., pH change_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., Competing Interests: The authors declare no competing financial interest., (© 2021 [The Author/The Authors].)

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.

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., (© 2020 Wiley-VCH GmbH.)

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 Eu 3+ ion. Fluorescence intensity of MA-TETA conjugate decreases with increasing Eu 3+ concentration indicating energy transfer from MA-TETA to Eu 3+ . 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Conventional systemic chemotherapeutic regimens suffer from challenges such as nonspecificity, shorter half-life, clearance of drugs, and dose-limiting toxicity. Localized delivery of chemotherapeutic drugs through noninvasive spatiotemporally controllable stimuli-responsive drug delivery systems could overcome these drawbacks while utilizing drugs approved for cancer treatment. In this regard, we developed photoelectro active nanocomposite silk-based drug delivery systems (DDS) exhibiting on-demand drug release in vivo. A functionally modified single-walled carbon nanotube loaded with doxorubicin (DOX) was embedded within a cross-linker free silk hydrogel. The resultant nanocomposite silk hydrogel showed electrical field responsiveness and near-infrared (NIR) laser-induced hyperthermal effect. The remote application of these stimuli in tandem or independent manner led to the increased thermal and electrical conductivity of nanocomposite hydrogel, which effectively triggered the intermittent on-demand drug release. In a proof-of-concept in vivo tumor regression study, the nanocomposite hydrogel was administered in a minimally invasive way at the periphery of the tumor by covering most of it. During the 21-day study, drastic tumor regression was recorded upon regular stimulation of nanocomposite hydrogel with simultaneous or individual external application of an electric field and NIR laser. Tumor cell death marker expression analysis uncovered the induction of apoptosis in tumor cells leading to its shrinkage. Heart ultrasound and histology revealed no cardiotoxicity associated with localized DOX treatment. To our knowledge, this is also the first report to show the simultaneous application of electric field and NIR laser in vivo for localized tumor therapy, and our results suggested that such strategy might have high clinical translational potential.

3D culture of stem cells can improve therapeutic effects. However, there is limited research on how to deliver cultured stem cell spheroids to the desired target. Here, we developed lotus seedpod-inspired hydrogel (LoSH) containing microwells for culture and delivery of stem cell spheroids. Human adipose-derived stem cells (hADSCs) inside the square microwells (200 or 400 μm in width with various depths) spontaneously formed spheroids with high viability (94.08 ± 1.56%), and fibronectins conjugated to the hydrogel successfully gripped the spheroids, similar to the funiculus gripping seeds in the lotus seedpod. The spheroids slightly bound to the LoSH surface at 37 °C were detached by the expansion of LoSH at lower temperature of 4 °C. After spheroid formation, LoSH was placed on the target substrate upside-down, expanded at 4 °C for 10 min, and removed from the target. As a result, the spheroids within the microwell were successfully transferred to the target substrate with high transfer efficiency (93.78 ± 2.30%). A delivery of spheroids from LoSH to full-thickness murine skin wound with chimney model showed significant enhancement of the number of SMA-positive vessels at day 21 compared to the group received the same number of spheroids by injection. Together, our findings demonstrate LoSH as a one-step platform that can culture and deliver spheroids to a large target area, which will be useful for various biomedical applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest.

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., Competing Interests: The authors declare no conflicts of interest.

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.

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., (© 2018 International Federation for Cell Biology.)

Polymers that confer changes in optical properties in response to chemical or mechanical cues offer diverse sensing applications, particularly if this stimuli response is accessible in humid or aqueous environments. In this study, luminescent hydrogels were fabricated using a facile aqueous process by incorporating lanthanide ions and carbon dots (CD) into a network of polyacrylamide and poly(acrylic acid). White luminescence was obtained by tuning the balance of blue-light-emitting CD to green- and red-light-emitting lanthanide ions. Exploiting the combined specific sensitivities of the different emitters, the luminescent hydrogel showed chromic responsiveness to multiple stimuli, including pH, organic vapors, transition-metal ions, and temperature. The white-light-emitting hydrogel was also stretchable with a fracture strain of 400%. We envision this photoluminescent hydrogel to be a versatile and multifunctional material for chemical and environmental sensing.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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±12.9kPa 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., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Poly- N -isopropylacrylamide (PNIPAAm) hydrogels, known for their sensor and actuator capabilities, can be photolithographically structured for microsystem applications. For usage in microsystems, the preparation, and hence the characteristics, of these hydrogels (e.g., degree of swelling, size, cooperative diffusion coefficient) are key features, and have to be as reproducible as possible. A common method of hydrogel fabrication is free radical polymerisation using a thermally-initiated system or a photoinitiator system. Due to the reaction quenching by oxygen, the polymer solution has to be rinsed with protective inert gases like nitrogen or argon before the polymerisation process. In this paper, we focus on the preparation reproducibility of PNIPAAm hydrogels under different conditions, and investigate the influence of oxygen and the UV light source during the photopolymerisation process. The flushing of the polymer solution with inert gas is not sufficient for photostructuring approaches, so a glove box preparation resulting in better quality. Moreover, the usage of a wide-band UV light source yields higher reproducibility to the photostructuring process compared to a narrow-band UV source.

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.