Scientific publications

Engineered living materials (ELMs) made of bacteria in hydrogels have shown considerable promise for therapeutic applications through controlled and sustained release of complex biopharmaceuticals at low costs and with reduced wastage. While most therapeutic ELMs use E. coli due to its large genetic toolbox, most live biotherapeutic bacteria in development are lactic acid bacteria due to native health benefits they offer. Among these, lactobacilli form the largest family of probiotics with therapeutic potential in almost all sites of the body with a microbiome. A major factor limiting the use of lactobacilli in ELMs is their limited genetic toolbox. This study expands on recent work to expand the genetic programmability of probiotic Lactiplantibacillus plantarum WCFS1 for protein secretion and encapsulate it in a simple, cost-effective, and biocompatible core–shell alginate bead to develop an ELM. The controlled release of recombinant proteins is demonstrated, even up to 14 days from this ELM, thereby terming it PEARL – Protein Eluting Alginate with Recombinant Lactobacilli. Notably, lactobacillus encapsulation offered benefits like bacterial containment, protein release profile stabilization, and metabolite-induced cytotoxicity prevention. These findings demonstrate the mutual benefits of combining recombinant lactobacilli with alginate for the controlled and sustained release of proteins.

The exceptional adhesion properties of biological fibrillar structures – such as those found in geckos – have inspired the development of synthetic adhesive surfaces. Among these, mushroom-shaped fibrils have demonstrated superior pull-off strength compared to other geometries. In this study, we employ a computational approach based on a Dugdale cohesive zone model to analyze the detachment behavior of these fibrils when adhered to a rigid substrate. The results provide complete pull-off curves, revealing that the separation process is inherently unstable under load control, regardless of whether detachment initiates at the fibril edge or center. Our findings show that fibrils with a wide, thin mushroom cap effectively reduce stress concentrations and promote central detachment, leading to enhanced adhesion. However, detachment from the center is not observed in all geometries, whereas edge detachment can occur under certain conditions in all cases. Additionally, we investigate the impact of adhesion defects at the fibril center, showing that they can significantly reduce pull-off strength, particularly at high values of the dimensionless parameter

Collagen matrix deposition is an important biomarker to predict the regenerative capacity of new biomaterials or the therapeutic potential of new drugs in collagen-associated diseases. Several methods for the quantification of matrix collagen in tissue samples are established, e.g., Picro-Sirius red assay, hydroxyproline assay, antibody-based assays, or the 3,4-DHPAA-based assay. These methods have been extended to quantify deposited collagen in in vitro cell culture models, although their applicability has been questioned due to the much lower concentration and eventually lower relative abundance of deposited collagen in cell cultures than in tissue. Here we compare the performance of the above-mentioned methods for the quantification of deposited matrix collagen in 2D cell cultures under different conditions: culture time, addition of collagen deposition-stimulating molecules, and post-culture processing step (decellularization). We show that the available methods can deliver accurate results within different experimental windows. We provide a comprehensive analysis of the relevant experimental parameters that influence the assay, and the sensitivity limits for the different methods, as well as the involved effort. In a comparative table, we provide guidance for the selection of the most appropriate collagen quantification assay for different culture conditions.

Antibiotic-resistant pathogens are a global health challenge, necessitating innovative solutions beyond conventional antibiotics. This study introduces biomimetic nanocarriers – hybrids of bacteriomimetic liposomes and biocompatible Myxobacteria outer-membrane vesicles (OMVs) – as tunable platforms for targeted antibiotic delivery. Comparative analyses of their physicochemical properties and interactions with immune cells, intestinal epithelium, and biofilm-forming pathogens reveal distinct advantages. Hybrids excel at delivering antibiotics to intracellular targets, while Myxobacteria OMVs, particularly those of strain SBSr 073, evade immune clearance and prolong extracellular drug exposure. To support clinical translation, this study optimizes antibiotic encapsulation methods for SBSr 073 OMVs and evaluates the short- and long-term impact of Cystobacter ferrugineus 23 strain OMVs on the gut microbiome in mice. Summing up, this study highlights the promise of Myxobacteria OMVs and their biomimetic hybrids as versatile tools for treating Gram-negative biofilm-forming pathogens. These findings underscore the potential of bioengineered and biomimetic drug carriers for combating antimicrobial resistance and pave the way for their translation toward difficult-to-treat infections.

Piezoresistive elastomer-based composites play a critical role in dielectric elastomer switches (DESs) for soft robotics, enabling mechanical strain-driven switching. While conventional liquid-based DES materials suffer from signal instability and poor long-term stability, particle-filled silicone composites offer greater signal stability and are durable but lack a strong piezoresistive response. The present article aims to enhance piezoresistivity by the alignment of graphite flakes in soft and stretchable silicone-based composites by using thin films. The electromechanical behavior was characterized through uniaxial tensile testing with in situ electrical resistance measurements. It is shown that films with thicknesses below 20 μm exhibit significantly stronger piezoresistive responses than bulk composites, with increases in resistance of up to four orders of magnitude at 40% strain at voltages up to 3 kV. Wide-angle X-ray scattering measurements elucidated that graphite flake alignment, resulting from the shear and physical confinement of flakes within thin films, plays a major role in enhancing the strain sensitivity. These findings indicate that graphite flakes/elastomer composites are promising materials for high-sensitivity DES applications. The ability to control piezoresistivity by the film thickness opens new possibilities for fully autonomous soft robotic systems with integrated sensing and actuation.

Blood-contacting medical devices play a crucial role in clinical interventions, but their susceptibility to thrombosis and inflammation poses serious risks to treatment outcomes and patient safety. This study presents a novel coating that combines dendritic polyglycerol amine (dPGA), dendritic polyglycerol aldehyde (dPG-CHO), and linear polyglycerol sulfate (lPGS) using a layer-by-layer self-assembly method (LBL) on a polystyrene surface. The immobilization of dendritic polyglycerol enhances surface coverage, enabling the incorporation of a higher density of heparin-mimicking lPGS, while the covalent bonding ensures the coating's long-term stability. Compared to the pristine substrate, the coating significantly reduced platelet adhesion and activation. Notably, its hemocompatibility effects persist even after 30 days. Furthermore, co-incubation experiments with RAW264.7 macrophages confirmed the anti-inflammatory properties of the polyglycerol-based coating. These results demonstrate that this heparin-mimetic coating effectively improves the hemocompatibility of polystyrene and has the potential to be applied to other blood-contacting materials.

Ether-based room-temperature sodium–sulfur (RT Na─S) batteries are a promising energy-storage system, yet hindered by the unregulated sulfur redox pathway, severe polysulfide shuttling and rapid capacity fading. Herein, highly unsaturated niobium-oxide sub-nanoclusters (≈0.7 nm) anchored on defective carbon black (NbOx-DCB) as a dynamic sulfur-conversion catalyst are introduced. The delocalized Nb d-electrons in the sub-nanocluster configuration create a mixed Nb4+/Nb5+ valence state that functions as a bidirectional electron reservoir, thereby enabling a distinct d-band-center self-regulation mechanism. The strong d–p orbital coupling enabled by a Nb4+-rich surface effectively captures sodium polysulfides and accelerates sulfur conversion kinetics during discharge, while a Nb5+-rich surface promotes facile solid-polysulfide decomposition during charging. Consequently, the NbOx-DCB/S cathode delivers a reversible capacity of 1184 mAh gS−1 at 0.1 A g−1 after 100 cycles and retains 547 mAh gS−1 after 3000 cycles at 2 A g−1, corresponding to a decay rate of 0.0027% per cycle. The general applicability of this approach is validated by high-performance tungsten and vanadium oxide sub-nanocluster-based sulfur cathodes. These findings highlight sub-nanoscale metal-oxide engineering as a versatile route to high-performance RT Na–S batteries.

Wearable electrochemical biosensors offer a promising alternative to conventional invasive blood-based methods for monitoring biomarkers in diagnostic or therapeutic applications. Microneedle (MN)-based technology provides direct access to the skin's interstitial fluid (ISF), enabling real-time monitoring of biomarkers. Nevertheless, current micro- and nanofabrication techniques do not adequately support the development of MN-based wearable technology that can utilize soft hybrid conductive inks, limiting its use in transdermal biosensing. Herein, an MN-based biosensing platform is developed by integrating 3D printing, soft lithography, and hybrid conductive ink technology, featuring a fenestrated MN shell (FMNS) that serves as a protective layer for the inner hybrid conductive ink coating and prevents delamination during skin application. This FMNS patch demonstrates a wide pH monitoring range, high selectivity and accurate detection of subtle ISF pH changes, safe integration of hybrid conductive inks, and reduced fabrication time and cost when compared to other microfabrication methods such as lithography and deep reactive ion etching. The biosensor excels in protecting the biosensing layer and demonstrates excellent analytical performance in monitoring changes in pH levels of the skin ISF. This micro- and nanofabrication approach has great potential in integrating hybrid conductive ink technology into transdermal wearable devices for health monitoring and diagnostics.

Synthetic cells have emerged as a novel biomimetic approach for studying fundamental cellular functions and enabling new therapeutic interventions. However, the potential to program synthetic cells into self-organized 3D collectives to replicate the structure and function of tissues has remained largely untapped. Here, self-assembly properties are engineered into synthetic cells to form millimeter-sized 3D lymphatic bottom-up tissues (lymphBUTs) with mechanical adaptability, metabolic activity, and hierarchical microstructural organization. It is demonstrated that primary human immune cells spontaneously infiltrate and functionally integrate into these synthetic lymph nodes to form living tissue hybrids. Applying lymphBUTs, it is shown that structured 3D organization and mechanical support drives T cell activation and the application of lymphBUTs for ex vivo expansion of regulatory CD8+ T cells is demonstrated. The study highlights the functional integration of living and non-living matter, advancing synthetic cell engineering toward 3D tissue structures.

For decades, polyglucosamine (PGA), also known as chitosan, has been used as an active ingredient in medical devices intended for body weight reduction and the control of blood lipid levels in obese patients, even though the exact mechanism of lipid binding still remains unclear. The binding capability of polyglucosamines towards dietary lipids is well documented in the literature and has been studied in-depth with respect to the physicochemical properties of the biopolymer. However, only a limited number of reliable correlations between the oil-binding capacity and material properties have been reported. In contrast, the morphology and structural nature of oil-polyglucosamine sponges have not received much attention and have been investigated only rudimentarily. Our work closes this gap and shines light on the pivotal step of structure formation and morphology in relation to oil-binding capacity. After the characterization of three batches of polyglucosamine via elemental and thermal analysis, infrared spectroscopy, and size exclusion chromatography, the oil binding capacity was determined over a range of oil-to-PGA ratios for one selected batch PGA21 (Mw = 251.6 kDa, DA = 4.3%). From the resulting oil-binding capacity, which turned out to be as high as 3,750 goil/g, a combination of variables C100 and Cmax was derived for more reliable material characterization. Furthermore, the prepared sponges were subjected to morphology investigations. Mild electron microscopy techniques, as well as confocal microscopy, were utilized to resolve the native three-dimensional network of polyglucosamine embedded in the oil matrix. After oil removal using a tailored solvent-exchange method, we were successful in resolving a highly porous, sponge-like structure featuring nanofibrils as the structural subunit. This delicate structure offered a high surface area, resulting in increased oil-binding capacity. From these findings, we derived that an interplay of morphological characteristics and molecular interactions leads to the ultra-high and structurally rigid oil-binding capacity of polyglucosamine.