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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.

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.

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.

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.