Scientific publications

Living therapeutics are attractive candidates to tackle the limitations of classically delivered therapeutic peptides, which are often poorly stable and require cost-intensive modifications. Their functional assessment is limited to animal experiments, which increase the complexity to evaluate the dynamic nature of these systems. Therefore, we developed an in vitro model of endotoxemia using macrophages to assess early-stage anti-inflammatory Living therapeutics. We refined the model based on three anti-inflammatory peptides (KCF-18, I6P7, and α-MSH) and identified suitable therapeutic concentrations and treatment durations. We applied the model to Lactiplantibacillus plantarum TF103, a probiotic engineered to secrete these peptides. The model revealed that Living therapeutics enhanced the effects of the peptides, requiring lower amounts of anti-inflammatory effects. This points to potential synergistic effects between peptides and bacteria. The model presented here allows the investigation of dynamic regimes, which could be useful in the development of complex systems such as the ones encountered in Living therapeutics.

Biodegradable polymers play a crucial role in biomedical applications, particularly as nanocarriers in drug delivery. While labeling the polymers with fluorescent dyes facilitates monitoring their biodistribution and post cellular uptake, tracking polymer degradation within biological systems remains a challenge. This raises important unanswered questions regarding the fate of the polymers, their degradation products, and the degree of their degradation within biological systems. In this study, we developed a novel dynamic biodynamer (BDP-Lys) composed of BODIPY and lysine-hydrazide monomers linked by reversible dynamic covalent bonds, designed to control the fluorescence of BODIPY by degradation. The BDP-Lys undergoes pH-responsive degradation, leading to recovery of quenched BODIPY and enhanced fluorescence emissions, thereby enabling direct monitoring of intracellular polymer degradation. Physicochemical characterization revealed its molecular weight, filament-like morphology, and a notable 12-fold increase in fluorescence intensity at acid-induced degradation. In vitro studies demonstrated excellent biocompatibility, efficient cellular uptake and a threefold increase in fluorescence due to polymer degradation in mammalian cells, resulting in a maximum of 17 % monomer release in the first 24 h. Thus, BDP-Lys emerges as a promising tool for exploring polymer behavior in biological systems, providing real-time insights into degradation and offering new opportunities to address unresolved questions in the field.

Increasing aging population, digital screen use, environmental factors, and sleep disorders have contributed to a rise in ophthalmic diseases. This has soared the demand for better ocular models that are more predictive and can be used to identify new pharmacological targets. Traditional models fail to recapitulate organ-level functionalities and present anatomical differences with human structures, therefore, organ-on-chip systems have emerged to tackle these limitations. Microfluidic devices is engineered to provide the layered structure that the ocular tissues require. This is combined with tight regulation of diffusion gradients and perfusion systems for toxicological analysis and drug screening applications. Incorporation of several cellular layers, motion to mimic blinking, or incorporation of ocular organoids in microfluidic devices are some of the advancements that the field has made. This work reviews the evolution of ocular microphysiological systems and discusses some challenges that could be undertaken by the organ-on-chip community.

The energy transition and the intermittent characteristic of renewable energy sources highlight the importance of materials research for energy storage systems. Hexacyanometalates (HCM) are promising candidates in energy storage systems due to their structure, capability of intercalating/extracting ions during the redox process, and the variety of synthesis techniques available. Among HCMs, nickel hexacyanoferrate (NiHCF) gains attention due to its long-life cycle and promising application in aqueous systems. Combining the properties of NiHCF along with freestanding films based on reduced graphene oxide (rGO) and polyaniline (PAni) offers a promising application in aqueous batteries as it includes both the electroactive material and the current collector in a single electrode. Herein, freestanding electrodes based on rGO/PAni/NiHCF are synthesized through the electrodeposition of NiHCF over rGO/PAni films, enabling control of the amount of NiHCF nanoparticles and the freestanding film thickness. Thinner electrodes achieve specific capacity values of 83 mAh g−1 at the current density of 50 mA g−1 in a three-electrode system, a specific capacity close to 61 mAh g−1 at the current density of 10 mA g−1 in a coin-cell system, approaching the theoretical capacity of NiHCF.

Endothelial cells (ECs) experience shear stress associated with blood flow. Such shear stress regulates endothelial function by altering cell physiology. Since most cell culture protocols and media compositions are designed for static cultures and experiments with ECs are predominantly conducted under these non-physiological conditions, a model for culturing ECs under flow conditions is developed, which more closely mimics their physiological environment. This approach also enables the isolation of EVs while minimizing FCS-derived contaminants. In this study, a comprehensive assessment of how physiologically relevant cultivation conditions influence the vesicle composition and function of ECs is provided. A detailed investigation is conducted for the effect of different cell culture media on morphology and marker expression of human umbilical cord endothelial cells (HUVECs) and EVs, and optimize the conditions to culture ECs under flow, tailoring them specifically to facilitate the efficient isolation of EVs using a hollow-fiber system model. These EVs are then characterized and compared to those isolated from traditional static culture conditions. Overall, this study presents a model on isolating EC-derived EVs under conditions that closely mimic physiological environments, and characterization at their proteome, gene expression, and microRNA profile.

Glaucoma, an eye disease causing incremental vision loss, currently has no cure. Its primary cause is the malfunction of the trabecular meshwork (TM), a multilayered tissue in the eye responsible for draining aqueous humor (AH) from the anterior chamber. TM clogging increases outflow resistance, elevates intraocular pressure (IOP), and damages optic nerves, leading to irreversible blindness. Existing in vitro TM models are suboptimal, as they lack the hierarchical structure of the TM. This article introduces a dynamic in vitro TM model, featuring a multilayered scaffold architecture 3D printed via melt electrowriting (MEW), and integrated with a flow system that enables continuous pressure monitoring during perfusion at native flow rates. Printed scaffolds supported the growth of primary adult human TM cells that grew on top and between the fibers. Cellularized scaffolds were tested under static and dynamic conditions. Over 3–5 days, pressure monitoring showed increased outflow resistance due to cell proliferation. Proteomic analysis revealed distinct changes in protein expression related to protein synthesis and respiration of cells grown under flow. Lat-B administration resulted in decreased pressure values and depolymerized actin filaments. These findings suggest that the proposed model is a promising alternative for in vitro glaucoma drug testing.

The potential of bioactive coatings as an innovative biotechnology to overcome the mass-transfer limitations of conventional technologies when treating air pollutants, especially hydrophobic volatile organic compounds, was herein assessed. Bioactive coatings consist of active microorganisms entrapped in a polymer matrix, which needs to be porous to facilitate an effective gas pollutant exchange. To increase porosity, two additives, sucrose and glycerol mixtures (Suc/Gly) and halloysite nanotubes (HNTs), were included in the bioactive coatings at two concentration levels. The toluene removals of the different bioactive coatings were studied in batch mode at low (∼300 mg m−3) and high (∼3000 mg m−3) toluene concentrations. Overall, low HNTs concentration coatings supported optimum toluene removals (>95 %), comparable to biofilm controls at both toluene concentrations. High HNTs concentration coatings and low Suc/Gly concentration coatings achieved toluene removals over 95 % after 7 toluene injections at low toluene concentration. At high toluene concentrations, these coatings eventually outperformed the biofilm controls. High Suc/Gly concentration coatings supported a limited toluene removal (4 and 1 injection at low and high toluene concentrations, respectively), attributed to a preferential consumption of sucrose over toluene. These findings were corroborated by ESEM/conventional SEM imaging, revealing porosity in the HNTs bioactive coatings, visible at both the surface and internal levels. On the contrary, more homogeneous surfaces were observed in the Suc/Gly bioactive coatings, where total polymer coalescence was partially hindered by the addition of Suc/Gly. These results paved the way towards the implementation of bioactive coating in larger bioreactors for real-life air purification.

Conductive polymer composites (CPCs) combine the stretchability of an elastomeric matrix with the electrical conductivity of a metallic filler. The 3D structure of this filler particle network (FPN) and the contact resistances between particles above percolation, key factors in the conductivity, are not well understood. Here, we introduce 3D reconstructions of FPNs of micron-sized spherical silver particles in polydimethylsiloxane from focused ion beam scanning electron microscopy tomography. Analysis of the tomographic images provides the length and number of parallel conductive paths. The results show that the average contact resistance drops five orders of magnitude when increasing the silver loading from 36 vol% to 53 vol%, highlighting its dominating role for macroscopic conductivity rather than network structure. This links to 33% larger average area-equivalent diameters of the contact spots. Diffusional tortuosity, a metric that quantifies flow restriction through narrow contact spots, proves that higher contact forces decrease current flow restrictions and thus, increase overall electrical conductivity. These conclusions are verified using a segregated CPC, and it is found that the addition of 20 vol%
of insulating fillers at a constant silver loading of 30 vol% increases the conductivity 37-fold and decreases the average contact resistance by two orders of magnitude.

Individuals with more elastic, more hydrated or smaller fingers usually show better performance in several passive touch tasks. In active touch, people use different exploratory procedures when evaluating object properties, and tune their exploratory parameters. For example, they indent stimuli to assess softness and optimize their peak forces to get relevant information. In this study, we aim to understand whether finger pad size, elasticity and hydration affect individuals' force-tuning and discrimination performance in active softness perception. Participants performed two softness tasks in two different sessions. In one session, hyaluronic acid was applied to their finger pads to soften it, in the other they received no treatment. We assessed individual elasticity and hydration values with cutometer and corneometer in each session, and measured finger pad size in three dimension by caliper. In each task, two pairs of stimuli were presented to the participants (Young's Modulus: 41.5 vs. 45.0; 28.7 vs. 31.3 kPa) who chose the softer stimulus. In the restricted task, they could apply force only up to 2 Newton, whereas there was no force limit in the unconstrained task. We found that participants with smaller finger pad size exerted less force in the restricted task and participants with more hydrated and elastic fingers exerted less force in the unconstrained task. The force-tuning disappeared in the unconstrained task when treatment was applied. These results indicate that people employ strategies according to their finger parameters and to the availability of cues whereas adaptation to treatment is likely to need longer practice.

Plant-inspired soft robots enable distributed environmental monitoring. Fliers, i.e. soft robots that are carried passively by the wind, can be effectively deployed and cover large areas and distances. State-of-the-art fliers for humidity sensing are largely composed of electronic components, which increase cost and generate electronic waste. Here, we introduce self-deployable and biodegradable fliers inspired by natural Ailanthus altissima seeds. These artificial fliers are composed of fluorescent, cellulose-based composites with sensing capabilities. The material is shaped into artificial seeds using scalable 3D extrusion processing. Red-emitting Mn2+-doped Er3+, Yb3+:NaYF4 nanoparticles in the composite provide a strong optical emission upon excitation at 980 nm wavelength. The cellulose matrix absorbs water, which quenches the intensity of fluorescence of the nanoparticles. Increasing humidity thus changes the color of the fluorescence emission from red to green. We used ratiometric sensing to detect the humidity of the surroundings.