Biology subjects

Gruber, P.

Publications and source records attributed to Gruber, P..

3 recordsLinked to original sources

bioRxiv2026

Soft-Robotic Magnetic Microfluidic Catheter for Delivery of Aqueous-Based Dual-Component Embolic Formulations

Transcatheter embolization requires materials that can be steered through tortuous vessels, solidify rapidly in situ, remain clearly visible under fluoroscopy, and, ideally, carry therapeutic cargo without harming tissue. To meet these requirements, we present a fully water-based, two-component PEI-PEG hydrogel delivered through a soft-robotic, microfluidic catheter that keeps the precursors separate until they meet in a millimetre-scale mixing chamber at the tip. Fast amide cross-linking converts the liquid pair into a self-supporting gel within seconds, eliminating organic solvents and preventing catheter blockage. By adjusting precursor ratio and flow regime, the gel's stiffness and viscosity can be tuned over orders of magnitude, with the same chemistry allowing to occlude both high-flow arteries and fragile micro-vessels. The platform was validated in three escalating models. First, in ex-vivo perfused human placenta, the hydrogel filled targeted branches without reflux or fragmentation, demonstrating controlled delivery in clinically relevant vasculature. Next, in three porcine embolizations, splenic, hepatic and ascending pharyngeal arteries, the material achieved stable, selective occlusion with no migration, vasospasm or recanalization, showing seamless compatibility with standard interventional workflows. Finally, in rats bearing orthotopic liver tumours, drug-loaded hydrogel delivered through the hepatic artery concentrated doxorubicin inside tumours while sparing healthy tissue, confirming its potential for precision chemoembolization. These results position the PEI-PEG hydrogel and microfluidic catheter as a unified, image-guided platform that couples robust mechanical occlusion with site-specific drug delivery, offering a biocompatible alternative to current liquid embolics and expanding the therapeutic reach of minimally invasive embolization procedures.

bioengineering↗

bioRxiv2023

Sulfate limitation increases specific pDNA yield in E. coli fed-batch processes

Plasmid DNA (pDNA) is a key biotechnological product whose importance became apparent in the last years due to its role as a raw material in the messenger ribonucleic acid (mRNA) vaccine manufacturing process. In pharmaceutical production processes, cells need to grow in the defined medium in order to guarantee the highest standards of quality and repeatability. However, often these requirements result in low product titer, productivity, and yield. In this study, we used constraint-based metabolic modeling to optimize the average volumetric productivity of pDNA production in a fed-batch process. We identified a set of 13 nutrients in the growth medium that are essential for cell growth but not for pDNA replication. When these nutrients are depleted in the medium, cell growth is stalled and pDNA production is increased, raising the specific and volumetric yield and productivity. To exploit this effect we designed a three-stage process (1. batch, 2. fed-batch with cell growth, 3. fed-batch without cell growth). The transition between stage 2 and 3 is induced by sulfate starvation. Its onset can be easily controlled via the initial concentration of sulfate in the medium. We validated the decoupling behavior of sulfate and assessed pDNA quality attributes (supercoiled pDNA content) in E. coli with lab-scale bioreactor cultivations. The results showed an increase in supercoiled pDNA to biomass yield by 33 % and an increase of supercoiled pDNA volumetric productivity by 13 % upon limitation of sulfate. In conclusion, even for routinely manufactured biotechnological products such as pDNA, simple changes in the growth medium can significantly improve the yield and quality. HighlightsO_LIGenome-scale metabolic models predict growth decoupling strategies. C_LIO_LISulfate limitation decouples cell growth from pDNA production. C_LIO_LISulfate limitation increases the specific supercoiled pDNA yield by 33 % and the volumetric productivity by 13 %. C_LIO_LIWe propose that sulfate limitation improves the biosynthesis of over 25 % of naturally secreted products in E. coli. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/527815v4_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@68fdccorg.highwire.dtl.DTLVardef@ee8e8dorg.highwire.dtl.DTLVardef@1d0f99eorg.highwire.dtl.DTLVardef@b42744_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2021

Sequential defects in cardiac lineage commitment and maturation cause hypoplastic left heart syndrome

BackgroundComplex molecular programs in specific cell lineages govern human heart development. Hypoplastic left heart syndrome (HLHS) is the most common and severe manifestation within the spectrum of left ventricular outflow tract obstruction defects occurring in association with ventricular hypoplasia. The pathogenesis of HLHS is unknown, but hemodynamic disturbances are assumed to play a prominent role. MethodsTo identify perturbations in gene programs controlling ventricular muscle lineage development in HLHS, we performed: i) whole-exome sequencing of 87 HLHS parent-offspring trios, ii) nuclear transcriptomics of cardiomyocytes from ventricles of 4 patients with HLHS and 15 controls at different stages of heart development, iii) single cell RNA sequencing and iv) 3D modeling in iPSCs from 3 patients with HLHS and 3 controls. ResultsGene set enrichment and protein network analyses of damaging de-novo mutations and dysregulated genes from ventricles of patients with HLHS suggested alterations in specific gene programs and cellular processes critical during fetal ventricular cardiogenesis, including cell-cycle and cardiomyocyte maturation. Single-cell and 3D modeling with iPSCs demonstrated intrinsic defects in the cell-cycle/UPR/autophagy hub resulting in disrupted differentiation of early cardiac progenitor lineages leading to defective cardiomyocyte-subtype differentiation/maturation in HLHS. Additionally, premature cell-cycle exit of ventricular cardiomyocytes from HLHS patients prevented normal tissue responses to developmental signals for growth leading to multinucleation/polyploidy, accumulation of DNA damage, and exacerbated apoptosis, all potential drivers of left ventricular hypoplasia in absence of hemodynamic cues. ConclusionsOur results highlight that despite genetic heterogeneity in HLHS, many mutations converge on sequential cellular processes primarily driving cardiac myogenesis, suggesting novel therapeutic approaches.

developmental biology↗