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Versatile sensing matrixes are essential for the development of enzyme-immobilized optical biosensors. A novel three-dimensional titanium dioxide nanotubes/alginate hydrogel scaffold is proposed for the detection of sweat biomarkers, lactate, and glucose in artificial sweat. Hydrothermally synthesized titanium dioxide nanotubes were introduced to the alginate polymeric matrix, followed by cross-linking nanocomposite with dicationic calcium ions to fabricate the scaffold platform. Rapid colorimetric detection (blue color optical signal) was carried out for both lactate and glucose biomarkers in artificial sweat at 4 and 6 min, respectively. The superhydrophilicity and the capillarity of the synthesized titanium dioxide nanotubes, when incorporated into the alginate matrix, facilitate the rapid transfer of the artificial sweat components throughout the sensor scaffold, decreasing the detection times. Moreover, the scaffold was integrated on a cellulose paper to demonstrate the adaptability of the material to other matrixes, obtaining fast and homogeneous colorimetric detection of lactate and glucose in the paper substrate when image analysis was performed. The properties of this new composite provide new avenues in the development of paper-based sensor devices. The biocompatibility, the efficient immobilization of biological enzymes/colorimetric assays, and the quick optical signal readout behavior of the titanium dioxide nanotubes/alginate hydrogel scaffolds provide a prospective opportunity for integration into wearable devices. The authors acknowledge support from Gobierno de Espana, Ministerio de Economia y Competitividad (Grant No. BIO2016-80417-P) (AEI/FEDER, UE), "Ministerio de Ciencia y Educacion de Espana" under grant PID2020-120313GB-I00/AIE/10.13039/501100011033 and the Basque Government (Grant IT1271-19). This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 766007. The authors convey their special thanks to SGIker of the University of the Basque Country (UPV/EHU) and Dr. Javier G. Inanez for the technical equipment facility support. F.B.-L. and L.B.-D. acknowledge the "Red de Microfluidica Espanola" RED2018102829-T.

We evaluate a series of thin-sheet hydrogel molecularly imprinted polymers (MIPs), using a family of acrylamide-based monomers, selective for the target protein myoglobin (Mb). The simple production of the thin-sheet MIP offers an alternative biorecognition surface that is robust, stable and uniform, and has the potential to be adapted for biosensor applications. The MIP containing the functional monomer N-hydroxymethylacrylamide (NHMAm), produced optimal specific rebinding of the target protein (Mb) with 84.9% (± 0.7) rebinding and imprinting and selectivity factors of 1.41 and 1.55, respectively. The least optimal performing MIP contained the functional monomer N,N-dimethylacrylamide (DMAm) with 67.5% (± 0.7) rebinding and imprinting and selectivity factors of 1.11 and 1.32, respectively. Hydrogen bonding effects, within a protein-MIP complex, were investigated using computational methods and Fourier transform infrared (FTIR) spectroscopy. The quantum mechanical calculations predictions of a red shift of the monomer carbonyl peak is borne-out within FTIR spectra, with three of the MIPs, acrylamide, N-(hydroxymethyl) acrylamide, and N-(hydroxyethyl) acrylamide, showing peak downshifts of 4, 11, and 8 cm−1, respectively.

Significance: Personalized medicine requires the tracking of an individual’s metabolite levels over time to detect anomalies and evaluate the body’s response to medications. Implanted sensors offer effective means to continuously monitor specific metabolite levels, provided they are accurate, stable over long time periods, and do no harm. Aim: Four types of hydrogel embedded with pH-sensitive sensors were evaluated for their accuracy, sensitivity, reversibility, longevity, dynamic response, and consistency in static versus dynamic conditions and long-term storage. Approach: Raman spectroscopy was first used to calibrate the intensity of pH-sensitive peaks of the Raman-active hydrogel sensors in a static pH environment. The dynamic response was then assessed for hydrogels exposed to changing pH conditions within a flow cell. Finally, the static pH response after 5 months of storage was determined. Results: All four types of hydrogels allowed the surface-enhanced Raman spectroscopy (SERS) sensors to respond to the pH level of the local environment without introducing interfering signals, resulting in consistent calibration curves. When the pH level changed, the probes in the gels were slow to reach steady-state, requiring several hours, and response times were found to vary among hydrogels. Only one type, poly(2-hydroxyethyl methacrylate) (pHEMA), lasted five months without significant degradation of dynamic range. Conclusions: While all hydrogels appear to be viable candidates as biocompatible hosts for the SERS sensing chemistry, pHEMA was found to be most functionally stable over the long interval tested. Poly(ethylene glycol) hydrogels exhibit the most rapid response to changing pH. Since these two gel types are covalently cross-linked and do not generally degrade, they both offer advantages over sodium alginate for use as implants.

Three-dimensional (3D) multi-cellular aggregates hold important applications in tissue engineering and in vitro biological modeling. Probing the intrinsic forces generated during the aggregation process, could open up new possibilities in advancing the discovery of tissue mechanics-based biomarkers. We use individually suspended, and tethered gelatin hydrogel microfibers to guide multicellular aggregation of brain cancer cells (glioblastoma cell line, U87), forming characteristic cancer 'ellipsoids'. Over a culture period of up to 13 days, U87 aggregates evolve from a flexible cell string with cell coverage following the relaxed and curly fiber contour; to a distinct ellipsoid-on-string morphology, where the fiber segment connecting the ellipsoid poles become taut. Fluorescence imaging revealed the fiber segment embedded within the ellipsoidal aggregate to exhibit a morphological transition analogous to filament buckling under a compressive force. By treating the multicellular aggregate as an effective elastic medium where the microfiber is embedded, we applied a filament post-buckling theory to model the fiber morphology, deducing the apparent elasticity of the cancer ellipsoid medium, as well as the collective traction force inherent in the aggregation process., ERC H2020 StG 758865 China Scholarship Council

Hypothesis Due to their highly retentive properties, innovative recently developed, semi-interpenetrated hydrogels made up of poly(vinyl pyrrolidone) (PVP) chains embedded in a poly(2-hydroxyethyl methacrylate) (p(HEMA)) network should be efficiently used as cleaning material for fragile and degraded paper artworks. In restoration practice, indeed the wet cleaning of these artworks is usually performed by immersion of paper in water, a procedure which may lead to several drawbacks, including paper fibers swelling and dissolution of water-soluble original components. Experiments This class of gels were yet presented in literature, but their interactions with paper materials and ability to be spiked with active enzymes (as cleaning agents), have not been analyzed. To establish the suitability of these hydrogels as paper cleaning materials, first, a rheological and microstructural characterization of the gels was performed. Moreover, diffusion of macromolecules inside gels was studied using fluorescence microscopy, to check if these innovative hydrogels can be used as carriers for hydrolytic enzymes. Indeed, pastes and glues are usually found in old paper artworks, and their removal is a very delicate operation that requires a selective action, which is granted by specific hydrolytic enzymes. At the same time, spectroscopic analyses on paper samples under investigation before and after cleaning treatment has been performed, thus assessing the capabilty of these gels as cleaning materials. Findings With the aim of demonstrating the versatility of these hydrogels, several case studies, i.e., the removal of grime and water-soluble cellulose degradation byproducts, the removal of animal glue and the removal of starch paste from real samples, are presented. Results obtained with these gels have been compared to those obtained by using another gel used for paper artworks cleaning, i.e., Gellan gel.

Significance: Currently, various scaffolds with immobilized cells are widely used in tissue engineering and regenerative medicine. However, the physiological activity and cell viability in such constructs might be impaired due to a lack of oxygen and nutrients. Photobiomodulation (PBM) is a promising method of preconditioning cells to increase their metabolic activity and to activate proliferation or differentiation. Aim: Investigation of the potential of PBM for stimulation of cell activities in hydrogels. Approach: Mesenchymal stromal cells (MSCs) isolated from human gingival mucosa were encapsulated in modified fibrin hydrogels with different thicknesses and concentrations. Constructs with cells were subjected to a single-time exposure to red (630 nm) and near-infrared (IR) (840 nm) low-intensity irradiation. After 3 days of cultivation, the viability and physiological activity of the cells were analyzed using confocal microscopy and a set of classical tests for cytotoxicity. Results: The cell viability in fibrin hydrogels depended both on the thickness of the hydrogels and the concentration of gel-forming proteins. The PBM was able to improve cell viability in hydrogels. The most pronounced effect was achieved with near-IR irradiation at the 840-nm wavelength. Conclusions: PBM using near-IR light can be applied for stimulation of MSCs metabolism and proliferation in hydrogel-based constructs with thicknesses up to 3 mm.

This work addresses the development of a compact paper-based enzymatic microfluidic glucose/O2 fuel cell that can operate using a very limited sample volume (≈35 µl) and explores the energy generated by glucose at concentrations typically found in blood samples at physiological conditions (pH 7.4). Carbon paper electrodes combined with a paper sample absorption substrate all contained within a plastic microfluidic casing are used to construct the paper-based fuel cell. The anode catalysts consist of glucose dehydrogenase and [Os(4,4′-dimethoxy-2,2′-bipyridine)2(poly-vinylimidazole)10Cl]+ as mediator, while the cathode catalysts were bilirubin oxidase and [Os(2,2′-bipyridine)2(poly-vinylimidazole)10Cl]+ as mediator. The fuel cell delivered a linear power output response to glucose over the range of 2.5–30 mM, with power densities ranging from 20 to 90 µW cm−2. The quantification of the available electrical power as well as the energy density extracted from small synthetic samples allows planning potential uses of this energy to power different sensors and analysis devices in a wide variety of in-vitro applications., Peter Ó Conghaile is thanked for synthesis of the redox polymers. Neus Sabaté acknowledges funding from the European H2020 Framework Programme (Grant Agreement 648518 - SUPERCELL - ERC 2014 CoG). Juan Pablo Esquivel would like to thank the support from Marie Curie International Outgoing Fellowship (APPOCS) within the 7th European Community Framework Programme. F. Javier del Campo acknowledges funding from the Spanish Ministry of Economy through the DADDi2 project (TEC2013-48506-C3). Dónal Leech acknowledges support from Grant number 607793 under the Bioenergy FP7-PEOPLE-2013-ITN Programme.