Biology subjects

Nuber, U. A.

Publications and source records attributed to Nuber, U. A..

4 recordsLinked to original sources

bioRxiv2026

Tube-in-tube oxygen saturator enabling precise and dynamic control of liquid-phase oxygen concentrations for human cell culture applications

This study demonstrates the feasibility of using a Teflon-AF-based tube-in-tube saturator for fast and precise adjustment of oxygen concentrations in liquids, extending its relevance to human cell culture applications beyond organ-on-chip systems. The system achieves high, near-saturation oxygen concentrations of the liquid phase, with performance influenced by various parameters such as temperature, volume flow rate, and tube length. We demonstrate that the tube-in-tube saturator exhibits high sensitivity to variations in these parameters at low oxygen concentrations, whereas this sensitivity diminishes as saturation is approached. To elucidate the underlying mass transfer processes, kinetic experiments were combined with computational fluid dynamics simulations. The simulation results are in good agreement with the experimental data, and the developed model enables a reliable prediction of oxygen concentrations in the liquid phase under varying operating conditions. Owing to its design, performance, versatility, and portability, this system introduces a new approach for the precise and rapid control of oxygen concentrations in liquids for microscale and macroscale human cell culture applications, offering seamless integration with natural vascular or artificial perfusion networks.

bioengineering↗

bioRxiv2025

Chromatin remodelling subunit SMARCB1 is implicated in dendrite development and complex brain functions

SMARCB1 encodes a core component of the BAF chromatin remodelling complex and pathogenic variants in this gene are associated with neurodevelopmental disorders such as Coffin-Siris syndrome. The relationship between altered SMARCB1 protein products and severe functional brain changes in Coffin-Siris syndrome remains largely unknown. We performed cellular, molecular, and behavioural analyses of a Coffin-Siris syndrome mouse model with a heterozygous nervous system-specific Smarcb1 mutation. In addition, we evaluated general cognitive abilities, as well as cognitive and behavioural functioning, in individuals with SMARCB1-related Coffin-Siris syndrome. Smarcb1 mutant mice exhibited deficits in fine motor coordination and balance, as well as impaired spatial learning and memory. Furthermore, these mice showed anxiety-like behaviours and agitation when exposed to novel environments. The detected behavioural abnormalities could indicate impaired decision-making, which results in impaired risk assessment. Comparable cognitive and behavioural deviations were identified in individuals with Coffin-Siris syndrome and SMARCB1 pathogenic variants. Our analysis of the Smarcb1 mouse model revealed structural alterations in the brain, including decreased dendritic length and complexity of dendritic trees. These alterations may explain the observed functional impairments. Notably, our finding of reduced Wasl transcripts in mutant Purkinje cell nuclei suggests that dysregulation of actin polymerization may be involved in the discovered dendritic defects. Taken together, we demonstrate a link between the chromatin remodelling complex component SMARCB1, complex brain functions, neuronal structure, and a key regulator of actin branching.

neuroscience↗

bioRxiv2025

Self-organized vascularized human liver spheroids: Serum-free culture conditions and use as tissue building blocks

Engineering vascularized human liver tissue for in vitro models and in vivo applications remains a major challenge. Here, we describe a scalable approach to generate human liver spheroids with self-organized, lumen-containing vascular networks and demonstrate their use as building blocks for fabricating vascularized tissue layers. Spheroids were formed from HepaRG liver cells, human umbilical vein endothelial cells (HUVECs), and adipose tissue-derived mesenchymal stem cells (MSCs). The inclusion of MSCs prevented spatial segregation of hepatic and endothelial compartments and enabled endothelial network formation. We present two media that are suitable for culturing these spheroids: a serum-reduced medium and a defined serum-free medium containing GibcoTM KnockOut serum replacement. These media supported the long-term maintenance of hepatocytes in a metabolically active, relatively mature state, as well as the persistence of endothelial networks. Endothelial cell identity and organization were confirmed by VE-cadherin and ICAM-2 immunostaining and by transmission electron microscopy, which revealed adherens junctions and luminal morphologies consistent with a capillary-like organization. Spheroid-derived HUVECs established anastomoses with external endothelial channels in microfluidic devices. Moreover, endothelial sprouts emerging from the spheroids formed inter-spheroid connections within permissive hydrogels (fibrin or collagen-methylcellulose), a process that depended on the inter-spheroid distance. Finally, we demonstrate the fabrication of planar tissue layers with vascularly interconnected spheroids. Together, we identify key conditions, including cellular ratios, medium formulations, biomaterials, and spatial design criteria that enable the generation and assembly of vascularized liver spheroids as scalable tissue building blocks for tissue engineering applications. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/684548v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1b8c8a2org.highwire.dtl.DTLVardef@7c0ed2org.highwire.dtl.DTLVardef@b10886org.highwire.dtl.DTLVardef@a6ab4f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

Computational design of artificial supply networks for engineered human tissue

The development of large-scale, three-dimensional human tissues is crucial for various applications in therapeutic tissue engineering, disease modeling, and drug testing. However, due to the diffusion limit of oxygen, the lack of functional vascular networks is a significant limitation in maintaining these engineered tissues in the laboratory. To address this challenge, we present a systematic, model-based design process for artificial supply networks that can ensure a sufficient supply of oxygen and nutrients to engineered human tissue. Our approach combines mathematical models of fluid dynamics, cell metabolism, and network properties to identify key parameters influencing the supply performance. We demonstrate the applicability and possibilities of this design process by simulating different network structures, including cuboid and rhombic do-decahedral honeycombs, under various conditions. Our results show that the structure of the artificial supply network, oxygen concentration, and solute flow within the network strongly influence cellular metabolic activity and viability. We also examine the effects of non-uniform cell density, channel blockage, and long channel length on the oxygen distribution inside the cell-containing tissue compartment. Our findings highlight the importance of considering these factors in the design of artificial supply networks for large-scale engineered human tissues. This study provides a promising approach for quickly exploring the vast design space of possible network structures under different conditions for desired cell and tissue states, ultimately contributing to the development of more efficient and effective tissue engineering strategies.

bioengineering↗