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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.)

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.)

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.)

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.)

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.)

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]

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]

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]

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]

• 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]

[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]

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 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]

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]

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]

This work reports the preparation of starch-based hydrogel nanocomposites that undergo changes in swelling behavior in response to both pH and a remotely applied magnetic field. The hydrogels were formed by ultrasound-induced radicalar cross-linking/polymerization of vinyl-modified starch with N ′, N ′-dimethylacrylamide (DMAAm) and acrylic acid (AAc) in the presence of CoFe 2 O 4 nanoparticles (average diameter of 365.5 ± 2.1 nm). Water transport properties were studied by applying swelling-based kinetic models. The effect of the magnetic field on the swelling potential was more prominent at pH 2 for hydrogel without AAc and the ionic nature of the polymer network was more important at pH 10 for hydrogel with AAc. At pH 2, the swelling mechanism for all hydrogels is described by a pseudo-Fickian transport, and is independent of the applied magnetic field. At pH 7 and pH 10, the hydrogels containing AAc showed anomalous mechanism, attributed to the anion–anion electrostatic repulsion forces. These hydrogels showed an increase in the swelling rate at higher pH. A significant increase in the swelling rate was also observed when the magnetic field is on, but this was verified only at pH 2. The hydrogels made of starch (0.5%), DMAAm (0.25%), and CoFe 2 O 4 (0.125% or 0.250%) underwent changes in swelling rate in response to an applied magnetic field, independently of pH. For these hydrogels, the magnetic properties of the nanoparticles were more important than their physical–chemical characteristics. Cytotoxicity research showed that the hydrogels have a great pharmacological potential for application in biological systems. [ABSTRACT FROM AUTHOR]

Biologically stimuli-responsive hydrogels, "biomolecule-responsive hydrogels', undergo changes in volume in response to a target biomolecule such as glucose, a protein, or DNA. Biomolecnle-responsive hydrogels have attracted considerable attention as novel smart biomaterials in the biomedical field because target biomolecules such as saccharides and proteins are useful signals for site-specific drug delivery systems or for monitoring physiological changes. There are several strategies for designing biomolecule-responsive hydrogels, which combine the ability to recognize a target molecule with the ability to induce a structural change in the hydrogel network. A standard strategy uses the combination of the molecular recognition events of biomolecules such as enzymes, lectins and antibodies with the responsive behavior of pH- or temperature-responsive polymers. We have proposed another strategy that utilizes biomolecular complexes like lectin-saccharide complexes and antigen-antibody complexes as dynamic crosslinks of hydrogel networks. This article reviews the relevant research of biomolecule-responsive hydrogels that were strategically designed by using the recognition functions of biomolecules such as enzymes, proteins, or DNA. [ABSTRACT FROM AUTHOR]

Abstract: A thermo and pH-responsive hydrogel (PNIPAM-co-PPAP) was synthesized via free radical polymerization of N-isopropylacrylamide (NIPAM) and potassium 4-(acryloyloxy) pyridine-2, 6-dicarboxylate (PAP) in mixed solvents of water and tetrahydrofuran. SEM micrographs revealed that the hydrogel was macroporous and the pores within the matrixes were interconnected. The chelidamic acid functionalized PNIPAM-co-PPAP hydrogel exhibited excellent capacity to anchor palladium (II) and the resulting material showed well catalytic activity for copper-free Sonogashira reaction of aryl halides with phenylacetylene in aqueous media. The reactions proceeded well with 0.1mol% of Pd (II) catalyst, due to the good dispersion of Pd2+ in the macroporous structure as well as the enrichment of reactants within hydrogel under reaction conditions. Through the reversibly swelling/deswelling, the PNIPAM-co-PPAP hydrogel-immobilized Pd (II) catalyst could be easily recovered by simple method. Furthermore, the PNIPAM-co-PPAP /Pd catalyst exhibited good recyclability and could be recycled six times without remarkable loss in catalytic activity. [Copyright &y& Elsevier]

Abstract: This review paper presents hydrogel-based devices for biomedical applications. The first part of the paper gives a comprehensive, qualitative, theoretical overview of hydrogels’ synthesis and operation. Crosslinking methods, operation principles and transduction mechanisms are discussed in this part. The second part includes applications of hydrogel devices in specific fields of interest. Sensing, fluid control, drug delivery, nerve regeneration and other biomedical applications constitute the main focus of this part. The aim of this paper is to briefly present recent advances of the field, without neglecting older ones, and to discuss important or novel concepts of each. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Intelligent drug delivery systems using UV polymerized hydrogels controlled by software were developed. The conditions of drug releases such as drug concentration, timing and amount of released drug could be controlled. It was also shown that the release threshold and the program design could be modified by IR data communication. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Two temperature and pH responsive submicron hydrogels based on poly(N- methylenebisacrylamide), chitosan and β-cyclodextrines (PNCS/CD hydrogel) with varying poly(N-isopropylacrylamide) to chitosan ratios were synthesized according to a simplified procedure, reflecting improved stimuli responsive properties and excellent bio-barrier properties, granted by incorporated chitosan. Hydrogels were applied to cotton-cellulose fabric as active coatings. Subsequently, antimicrobially active savory essential oil (EO) was embedded into the hydrogels in order to develop temperature- and pH-responsive cotton-cellulose fabric with double antimicrobial activity, i.e., bio-barrier formation of chitosan along with the proactive release of savory EO at predetermined conditions. The influence of the hydrogels chemical composition on stimuli responsive and antibacterial properties were assessed. Both PNCS/CD hydrogels showed stimuli responsiveness along with controlled release of savory EO. The chemical composition of the hydrogels strongly influenced the size of the hydrogel particles, their temperature and pH responsiveness, and the bio-barrier forming activity. The increased concentration of chitosan resulted in superior overall stimuli responsiveness and excellent synergy between the antimicrobial activities of the hydrogel and released savory EO. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]