Scientific publications

Selective aggregation of gold and silver nanoparticles in water, leading to distinctly coloured states, can be achieved using particles with suitable ligands and bis(cyclodextrins) as the linking units.

Soft electrical components are highly demanded for human-machine interaction devices. “Electrofluids” (EFs), which are suspensions of electrically conductive filler particles in non-conductive solvents, are proposed as promising sensors and conductive materials since they can flow and retain electrical conductivity. As they remain liquid in working conditions, encapsulation and manufacturing of complex patterns remain as a challenge but would enable a wider variety of applications. Direct ink writing (DIW) is proposed here as a method to manufacture carbon-based EFs. Simple shear flow and Fourier-transform (FT) rheology are performed to evaluate the printability of EFs containing different concentrations of Carbon Black and Graphene Powder by DIW. Electrofluids exhibited three important characteristics to be manufactured via DIW: yield stress behavior (confirmed by flow curves), high brittleness, and a fast mechanical recovery within a range of 15 s. Printability maps are created to distinguish printable and non-printable EFs. Printable EFs are used to manufacture complex patterns. As a proof of the great potential of the EFs and DIW combination, a comparison between simple and multiline strain gauges showed an enhancement in the sensitivity of EFs as strain sensors by almost 800%.

The perceived time can shrink or expand for emotional stimuli. Converging evidence suggests that emotional
time distortions are rooted in the emotional states of the timing agents because emotional stimuli can influence
the timing of simultaneous neutral events. As emotional states are transitory, we investigated if time modulating
emotional states also influence timing of subsequent neutral events. In each trial, we induced different valence
and arousal levels by using affective vibrotactile patterns before participants judged the duration of neutral
auditory tones. Compared to neutral patterns, affective patterns modulated participants’ time perception of the
subsequent tones. We observed an interaction between arousal and valence: Pleasant-Low arousal patterns
expanded the timing of subsequent neutral events more than Unpleasant-Low arousal patterns while Pleasant and
Unpleasant-High arousal led to a similar temporal expansion. Our results indicate time modulating effects of
emotional stimuli are due to changed emotional states and influence time perception likely until the underlying
state decays.

The approval of Onpattro® (2018) and Comirnaty (2020) has driven interest in nanoparticulate nucleotide delivery. Newer concepts in gene therapy however, require not only the delivery of one, but multiple nucleotides. Examples are CRISPR/Cas9 gene editing and cancer immunotherapy. However, the current gold standard for nucleotide delivery – lipid nanoparticles – faces significant challenges, including limitations for co-encapsulation and nucleotide-nucleotide interactions. Aim of this study was to design a core-shell system featuring separate encapsulation of two nucleotides via a two-step formulation process. Six distinct cationic polymers were combined with three anionic polymers, resulting in 18 core compositions. Screening of these formulations identified three potent lipopolyplexes (LPPs), which were further evaluated and compared in terms of transfection efficiency, expression kinetics, storage stability, and nebulization performance. Among them, the combination of poly-L-arginine and poly-L-glutamic acid demonstrated the highest overall performance. Our systems enabled precise co-delivery of two model mRNAs in a controlled ratio, demonstrating potential for advanced therapeutic applications. Additionally, the role of mRNA localization within the LPP was investigated. Surface-loaded mRNA demonstrated superior transfection efficiency and shear resistance compared to core-loaded mRNA, which lost functionality under nebulization.

Advances in the past decades in materials science, biofabrication methods, and synthetic biology have given rise to new fields like living materials. A living material is a class of biohybrid composite with living elements, including bacteria, yeasts, fungi, and mammalian cells, integrated with nonliving components. (1−6) These materials combine the advantages of both living and nonliving components to generate novel functions such as responses to environmental parameters and syntheses of complex biomolecules. (7) The nonliving aspect combines diverse chemistries and manufacturing techniques to support or enhance the functions of the living part. (6) Living materials as therapeutics (Living Therapeutic Materials, LTMs) bring revolutionary options to diagnostic and therapeutic practice, offering a solution to life-concerning issues by life itself (Figure 1). Living Therapeutic Materials are revolutionizing classical drug delivery devices, as they can produce therapeutics long-term, in situ, and on demand. This represents a more sustainable way for treatment. To realize Living Therapeutic Materials in the clinic, more preclinical studies need to be carried out so the concerns in terms of safety are well understood and their capacity as a more efficient delivery system is assessed. In the past decade, there has been a rise in the number of proof-of-concept LTMs and yet, the preclinical investigation of these materials is just starting.

The oxidation of triphenylphosphine by perfluorinated phenaziniumF aluminate in difluorobenzene affords hexaaryl-1,2-diphosphonium dialuminate 1. Dication 12+ is valence isoelectronic with elusive hexaphenylethane, where instead the formation of a mixture of the trityl radical and Gomberg’s dimer is favored. Quantum-chemical calculations in combination with Raman/IR spectroscopies rationalize the stability of the P–P bonded dimer in 12+ and suggest, akin to the halogens, facile homolytic as well as heterolytic scission. Thus, 12+ serves as a surrogate of both the triphenylphosphorandiylium dication (Ph3P2+) and the triphenylphosphine radical monocation (Ph3P·+). Treating 1 with dimethylaminopyridine (DMAP) or tBu3P replaces triphenylphosphine under heterolytic P–P bond scission. Qualifying as a superoxidant (E vs Fc/Fc+ = +1.44 V), 1 oxidizes trimethylphosphine. Based on halide abstraction experiments (–BF4, –PF6, –SbCl6, –SbF6) as well as the deoxygenation of triethylphosphine oxide, triflate anions as well as toluic acid, 1 also features Lewis superacidity. The controlled hydrolysis affords Hendrickson’s reagent, which itself finds broad use as a dehydration agent. Formally, homolytic P–P bond scission occurs with diphenyldisulfide (PhSSPh) and the triple bonds in benzo- and acetonitrile. The irradiation by light cleaves the P–P bond homolytically and generates transient triphenylphosphine radical cations, which engage in H-atom abstraction as well as CH phosphoranylation.

During mating in budding yeast, cells use pheromones to locate each other and fuse. This model system has shaped our current understanding of signal transduction and cell polarization in response to extracellular signals. The cell populations producing extracellular signal landscapes themselves are, however, less well understood, yet crucial for functionally testing quantitative models of cell polarization and for controlling cell behavior through bioengineering approaches. Here we engineered optogenetic control of pheromone landscapes in mating populations of budding yeast, hijacking the mating-pheromone pathway to achieve spatial control of growth, cell morphology, cell-cell fusion, and distance-dependent gene expression in response to light. Using our tool, we were able to spatially control and shape pheromone gradients, allowing the use of a biophysical model to infer the properties of large-scale gradients generated by mating populations in a single, quantitative experimental setup, predicting that the shape of such gradients depends quantitatively on population parameters. Spatial optogenetic control of diffusible signals and their degradation provides a controllable signaling environment for engineering artificial communication and cell-fate systems in gel-embedded cell populations without the need for physical manipulation.

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.