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Item type:Publication, Access status: without files , Development of a 3d-gingival wound model using collagen in the field of oral and maxillofacial surgeryPublicationtype: Journal Article4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Impact of CPPs on primary human NK cell CQAs during cell expansion – an experimental study using design of experiments(Frontiers Media SA, 2026-07-01); ; ; 4 3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Bioprocess monitoring: How much do we need to know for successful scale-up?To address the challenges posed by climate change and the demand for sustainable production, robust and efficient bioprocesses are alternatives to conventional chemical processes. However, many promising bioprocesses that perform well at laboratory scale fail upon scale-up to industrial scale. This discrepancy among other arises from environmental gradients in large scale bioreactors causing phenotypic population heterogeneity, metabolic burden, and genetic instability. Traditional assumptions of homogeneous cell behavior under well-mixed conditions are challenged by complex intracellular networks and spatial-temporal environmental variations, necessitating a multi-level bioprocess monitoring approach. This chapter reviews bioprocess monitoring strategies across hierarchical cell-physiological levels and discusses physical, chemical, and biological parameters critical for bioprocess understanding and control. It highlights measurement techniques, from in-line sensors enabling real-time control to off-line comprehensive analyses, and contrasts laboratory-scale flexible, multi-level monitoring with industrial-scale demands for robust, cost-effective, and regulative-compliant systems. Bridging the monitoring gap between scales involves applying “beginning-with-the-end-in-mind” in bioprocess design, integrating advanced monitoring such as single-cell analysis, scalable in-line sensors, and multi-level bioprocess modeling. Combining experimental data with computational models predicts scale-dependent cellular behavior, guides bioprocess optimization, and enables soft sensor development for real-time, automated closed-loop industrial bioprocess control. This integrated framework promises improved scale-up and enhanced robustness in industrial-scale bioprocesses.Publicationtype: Book Part4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Bioengineering strategies to enhance myoglobin expression in 3D C2C12 muscle constructs(2026); Developing physiologically relevant in vitro models of skeletal muscle tissue remains a central and persistent challenge across tissue engineering, regenerative medicine, and cultivated meat research. A critical barrier to achieving both scalability and advanced function is the absence of a simple, cost-effective fabrication strategy, coupled with insufficient clarity regarding the control mechanisms governing tissue maturation and key metabolic parameters like oxygenation. Myoglobin, the crucial oxygen-binding protein in muscle, serves as a vital functional biomarker for metabolic capacity and tissue maturity. This thesis directly addresses these fundamental obstacles through three integrated studies. First, a novel, scaffold-free protocol was successfully developed for fabricating three-dimensional (3D) skeletal muscle constructs with good structural integrity from C2C12 myoblasts. This innovative method leverages a spontaneous delamination phenomenon induced solely by serum starvation, offering a distinct advantage in simplicity and cost-effectiveness over conventional techniques. The resulting constructs were characterized for high viability, structural integrity determined via histology and scanning electron microscopy, and successful myogenic differentiation confirmed through myosin heavy chain expression. Second, to overcome inherent scalability limitations, computational modeling was integrated computational modeling with meticulous experimental validation to estimate a critical size constraint for these dense, cell-only constructs. Finite element simulations, validated by experimental measurements, established a maximum viable thickness of 5 mm based on the model's prediction that oxygen concentration at the construct's core would drop to zero at this boundary. This constraint is fundamentally driven by the inherent biophysical characteristics of the engineered tissue, thus establishing an important, data-informed design parameter for all future upscaling efforts. Finally, a a broad range of biochemical and physical parameters was systematically investigated to enhance myoglobin protein synthesis, the central indicator of tissue maturation and coloration. The findings showed that myoglobin synthesis is not solely driven by supplementation with iron, creatine, or Insulin-like Growth Factor-I (IGF-I), but is instead profoundly regulated by the physical and chemical microenvironment. Specifically, culture vessel size was inversely correlated with myoglobin content, with smaller vessels yielding significantly higher levels. Controlled bioreactor experiments identified a moderate dissolved oxygen (DO) concentration of 30 % air saturation as most favorable for myoglobin synthesis. Furthermore, applying a cyclic mechanical stretching regimen, when combined with optimal DO, induced a synergistic increase in myoglobin levels, resembling physiological responses to muscle exercise. Altogether, this work presents an integrated framework to creating, optimizing, and functionally enhancing scaffold-free muscle constructs. Four critical parameters, culture vessel size, culture time, dissolved oxygen levels, and mechanical stimulation, were identified that collectively govern myoglobin synthesis. These findings provide a useful foundation for developing physiologically relevant engineered muscle constructs with potential applications, from disease modeling to sustainable food production.Publicationtype: Doctoral Thesis40 15 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , A globular protein exhibits rare phase behavior and forms chemically regulated orthogonal condensates in cells(Nature Publishing Group, 2025-12-01); ; ; Proteins with chemically regulatable phase separation are of great interest in the fields of biomolecular condensates and synthetic biology. Intrinsically disordered proteins (IDPs) are the dominating building blocks of biomolecular condensates which often lack orthogonality and small-molecule regulation desired to create synthetic biomolecular condensates or membraneless organelles (MLOs). Here, we discover a well-folded globular protein, lipoate-protein ligase A (LplA) from E. coli involved in lipoylation of enzymes essential for one-carbon and energy metabolisms, that exhibits structural homomeric oligomerization and a rare LCST-type reversible phase separation in vitro. In both E. coli and human U2OS cells, LplA can form orthogonal condensates, which can be specifically dissolved by its natural substrate, the small molecule lipoic acid and its analogue lipoamide. The study of LplA phase behavior and its regulatability expands our understanding and toolkit of small-molecule regulatable protein phase behavior with impacts on biomedicine and synthetic biology.Publicationtype: Journal Article24 15 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Monitoring of the single-cell behavior of an escherichia coli reporter strain producing L-phenylalanine in a scale-down bioreactor by automated real-time flow cytometry(Multidisciplinary Digital Publishing Institute (MDPI), 2025-07-03); ; Large-scale bioprocesses often suffer from spatial heterogeneities, which impact microbial performance and often lead to phenotypic population heterogeneity. To better understand these effects at the single-cell level, this study applied, for the first time, automated real-time flow cytometry (ART-FCM) to monitor L-phenylalanine production with an <i>Escherichia coli</i> triple reporter strain in a fed-batch process with glycerol as the carbon source. The strain was cultivated in both a well-mixed stirred-tank bioreactor (STR) and a scale-down two-compartment bioreactor (TCB), consisting of an STR and a coiled flow inverter (CFI) in bypass, to simulate spatial heterogeneities. ART-FCM enabled autonomous, high-frequency sampling every 20 min, allowing for real-time tracking of fluorescence signals linked to growth (<i>rrnB</i>-mEmerald), oxygen availability (<i>narGHIJ</i>-CyOFP1), and product formation (<i>aroFBL</i>-mCardinal2). The STR exhibited uniform reporter expression and higher biomass accumulation, while the TCB showed delayed product formation and pronounced phenotypic diversification depending on the set mean residence time in the CFI. Single-cell fluorescence distributions revealed that the shorter mean residence time in the CFI resulted in pronounced subpopulation formation, whereas longer exposure attenuated heterogeneity, indicating transcriptional adaptation. This finding highlights a critical aspect of scale-down studies: increased exposure duration to perturbations can enhance population robustness. Overall, this study demonstrates the relevance of ART-FCM, in combination with a multi-reporter strain, as a pioneering tool for capturing dynamic cellular behavior and correlating it to process performance, providing deeper insights into microbial heterogeneity under fluctuating bioprocess conditions.Publicationtype: Journal Article44 19 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , The 11th International Congress on Biocatalysis (biocat2024), Hamburg, Germany, 25-29 August 2024(Multidisciplinary Digital Publishing Institute (MDPI), 2025-06-10); ; ; ; The "11th International Congress on Biocatalysis (biocat2024)" was part of a biennial series that unites the fields of biology and chemistry, attracting researchers from the life sciences, engineering, and computer science. This international forum provides an opportunity for scientists worldwide to connect, seek collaboration for future projects, and gain insights into contemporary topics and innovative techniques. Biocat covers a range of compelling subjects and recent advancements in biocatalysis, including enzyme discovery, evolution, and applications. This congress focused on six key topics: AI and computational methods, structure–function analysis and enzyme engineering, enzymatic and whole-cell biotransformations, reaction cascades (electro-, chemo-, and photoenzymatic synergies), bioprocess engineering and the design of smart reactors, and facing climate change through sustainability and a circular bioeconomy. In 2024, we welcomed 344 expert delegates alongside 21 internal attendees, including 154 women and 1 non-binary participant, bringing the total number of participants to an impressive 365. Established researchers and emerging scientists from academia and industry delivered a total of 119 presentations, comprising 59 standard lectures, 60 lightning talks, and 195 posters. Six industry exhibitors showcased their latest products and services, providing an excellent opportunity to strengthen the connection between science and industry. Furthermore, the biocat award, recognized as one of the most prestigious honors in biotechnology, was presented for the eleventh time in the categories of "Science in Academia", "Lifetime Achievement" and "Industry".Publicationtype: Journal Article49 38 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Scale-down bioreactors—comparative analysis of configurations(Springer, 2025-06-05); 33 23 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Digitale Zwillinge und ihre Rolle im modellgestützten Design von ExperimentenSteigende Nachfrage nach Biopharmazeutika und die Notwendigkeit, die Herstellungskosten zu senken, erhöhen den Druck, produktive und effiziente Bioprozesse zu entwickeln. Unter anderem ist ein großes Hindernis bei der Prozessentwicklung und Optimierungsstudien der enorme experimentelle Aufwand bei herkömmlichen Methoden des Design of Experiments (DoE). Da DoE ein explorativer Ansatz ist, erfordert es umfangreiches Expertenwissen über die untersuchten Faktoren und deren Grenzwerte und führt oft zu mehreren Runden zeitaufwändiger und kostspieliger Experimente. Die Kombination von DoE mit einer virtuellen Darstellung des Bioprozesses, genannt digitaler Zwilling, in modellgestütztem DoE (mDoE) kann als Alternative verwendet werden, um die Anzahl der Experimente erheblich zu reduzieren. mDoE ermöglicht eine wissensbasierte Bioprozessentwicklung, einschließlich der Definition eines mathematischen Prozessmodells in den frühen Entwicklungsstadien. In diesem Kapitel werden digitale Zwillinge und ihre Rolle in mDoE diskutiert. Zuerst werden statistische DoE-Methoden als Grundlage von mDoE eingeführt. Zweitens wird die Kombination eines mathematischen Prozessmodells und DoE zu mDoE untersucht. Dies umfasst mathematische Modellstrukturen und ein Auswahlverfahren für die Wahl der DoE-Designs. Schließlich wird die Anwendung von mDoE in einer Fallstudie zur Medienoptimierung in einem antikörperproduzierenden Zellkulturprozess von chinesischen Hamster-Ovarien diskutiert.Publicationtype: Book Part21 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: with files , Hybrid biological hydrogel provides favorable bioenergetic, adhesive, and antioxidative effects on wound healing(American Chemical Society (ACS), 2025-05-18); ; Wound healing is a dynamic and complex process that demands substantial energy expenditure and a biomimetic microenvironment. Developing a simple and effective biological hydrogel to enhance mitochondrial energy metabolism could effectively promote wound healing. To this end, we developed a hybrid biological hydrogel based on Escherichia coli lipoate protein ligase A (LplA), which combines its catalytic and self-assembling properties to promote wound healing. In murine fibroblast L929 cell models, LplA significantly enhances cellular activity and intracellular metabolism, promoting cell proliferation and energy supply. However, cells aggregated into spherical clusters on the pure LplA hydrogel. To address this issue, we integrated glutaraldehyde (GA) as a cross-linker into the LplA hydrogel. The GA-LplA hydrogel enhances cell adhesion and proliferation and, unexpectedly, exhibits higher catalytic activity compared with the pure LplA hydrogel. Furthermore, LplA was observed to decompose H2O2, and the GA-LplA hybrid hydrogel significantly reduced reactive oxygen species (ROS) production. The promise of this hybrid hydrogel is successfully demonstrated in a male mice full-thickness skin defect model with accelerated re-epithelialization and cell proliferation while reducing inflammation.Publicationtype: Journal Article17 10