Biology subjects

Weisskopf, M.

Publications and source records attributed to Weisskopf, M..

6 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↗

bioRxiv2026

Dynamic Nanoparticle Assembly-Based Biomedical Microrobots

Precise drug delivery within anatomically complex tissues demands systems capable of both active navigation and deep tissue access, properties that have remained difficult to reconcile in existing nanocarriers and microrobots. Here we introduce Dynabots, a dynamic microrobotic assembly constructed from multifunctional nanoparticles covalently linked by thermally cleavable molecular connectors. This nanoparticle-rich architecture enables the integration of magnetic, imaging, and therapeutic components while preserving a high content of functional material. Collective assembly imparts enhanced magnetic responsiveness and maneuverability, enabling controlled navigation through tortuous biological environments. Upon exposure to mild thermal stimuli, the assemblies undergo programmed disassembly, releasing individual nanoparticles that can diffuse through tissue for localized therapeutic action. We establish the programmable transitions, biocompatibility, and therapeutic efficacy of this process across in vitro and in vivo models, including real-time fluoroscopic guidance within anatomically realistic phantoms and live rodent and porcine systems. By integrating magnetic control, reconfigurable architecture, and stimulus-triggered disassembly, Dynabots unite navigational precision with tissue permeability, providing a versatile platform for adaptive and deep-tissue drug delivery.

bioengineering↗

bioRxiv2025

Volumetric 3D Printing and Melt-Electrowriting to Fabricate Implantable Reinforced Cardiac Tissue Patches

Cardiac patches for repairing myocardial defects require mechanically stable materials that prevent bleeding and can be implanted via suturing. The current clinical standard, bovine pericardial patches (BPPs), serve this purpose but do not degrade or integrate with the myocardium, limiting their long-term effectiveness. Therefore, we have developed the Reinforced engineered Cardiac tissue Patch (RCPatch). This multimaterial patch consists of a stiffness-tuned, cardiomyocyte-infiltrated 3D metamaterial and a suturable, hydrogel-infiltrated mesh to reduce permeability and bleeding. We first designed and computationally optimized anisotropic metamaterials using a generative modelling approach and fabricated them from biodegradable poly({varepsilon}-caprolactone) (PCL) via volumetric 3D printing (VP). The metamaterial supported the infiltration of cardiomyocytes, which maintained cell viability and contractility in vitro. In a second step, we enhanced implantability and reduced blood permeability through the patch by combining a melt-electrowritten (MEW) mesh with a fibrin hydrogel. Finally, in an acute large animal trial, the RCPatch was used on an induced myocardial defect, where it withstood intraventricular blood pressure and enabled partial hemodynamic recovery. Our findings establish a scalable framework for fabricating cardiac tissue patches that integrate mechanical reinforcement with biological function, offering a surgically implantable, and potentially regenerative solution for intraventricular myocardial repair. Table of Contents (ToC) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/642643v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@66293dorg.highwire.dtl.DTLVardef@11d9122org.highwire.dtl.DTLVardef@235d16org.highwire.dtl.DTLVardef@1b46911_HPS_FORMAT_FIGEXP M_FIG C_FIG This study presents an implantable intraventricular cardiac patch (RCPatch) combining volumetric 3D-printed metamaterials with melt-electrowritten (MEW) meshes. The design integrates tunable stiff structures with soft, cell-laden hydrogels. The RCPatch withstood suturing, intraventricular pressure, and cardiac contraction in an acute large animal myocardial defect model. The patch prevented bleeding and enabled partial hemodynamic recovery, demonstrating its potential for myocardial repair.

bioengineering↗

bioRxiv2021

Large portion of essential genes is missed by screening either fly or beetle indicating unexpected diversity of insect gene function

Most gene functions were detected by screens in very few model organisms but it has remained unclear how comprehensive these data are. Here, we expanded our RNAi screen in the red flour beetle Tribolium castaneum to cover more than half of the protein-coding genes and we compared the gene sets involved in several processes between beetle and fly. We find that around 50 % of the gene functions are detected in both species while the rest was found only in fly (~10%) or beetle (~40%) reflecting both technical and biological differences. We conclude that work in complementary model systems is required to gain a comprehensive picture on gene functions documented by the annotation of novel GO terms for 96 genes studied here. The RNAi screening resources developed in this project, the expanding transgenic tool-kit and our large-scale functional data make T. castaneum an excellent model system in that endeavor.

genetics↗

bioRxiv2018

A large-scale systemic RNAi screen in the red flour beetle Tribolium castaneum identifies novel genes involved in arthropod muscle development

Although muscle development has been widely studied in Drosophila melanogaster there are still many gaps in our knowledge, and it is not known to which extent this knowledge can be transferred to other insects. To help in closing these gaps we participated in a large-scale RNAi screen that used the red flour beetle, Tribolium castaneum, as a screening platform. The effects of systemic RNAi were screened upon double-stranded RNA injections into appropriate muscle-EGFP tester strains. Injections into pupae were followed by the analysis of the late embryonic/early larval muscle patterns, and injections into larvae by the analysis of the adult thoracic muscle patterns. Herein we describe the results of the first-pass screens with pupal and larval injections, which covered ~8,500 and ~5,000 genes, respectively, of a total of ~16,500 genes of the Tribolium genome. Apart from many genes known from Drosophila as regulators of muscle development, a collection of genes previously unconnected to muscle development yielded phenotypes in larval body wall and leg muscles as well as in indirect flight muscles. We then present the main candidates from the pupal injection screen that remained after being processed through a series of verification and selection steps. Further, we discuss why distinct though overlapping sets of genes are revealed by the Drosophila and Tribolium screening approaches.

developmental biology↗

bioRxiv2016

foxQ2 evolved a key role in anterior head and central brain patterning in protostomes

Anterior patterning of animals is based on a set of highly conserved transcription factors but the interactions within the protostome anterior gene regulatory network (aGRN) remain enigmatic. Here, we identify the foxQ2 ortholog of the red flour beetle Tribolium castaneum as novel upstream component of the insect aGRN. It is required for the development of the labrum and higher order brain structures, namely the central complex and the mushroom bodies. We reveal Tc-foxQ2 interactions by RNAi and heat shock-mediated misexpression. Surprisingly, Tc-foxQ2 and Tc-six3 mutually activate each other forming a novel regulatory module at the top of the insect aGRN. Comparisons of our results with those of sea urchins and cnidarians suggest that foxQ2 has acquired functions in head and brain patterning during protostome evolution. Our findings expand the knowledge on foxQ2 gene function to include essential roles in epidermal development and central brain patterning.\n\nAuthor summaryThe development of the anterior most part of any animal embryo - for instance the brain of vertebrates and the head of insects - depends on a very similar set of genes present in all animals. This is true for the two major lineages of bilaterian animals, the deuterostomes (including sea urchin and humans) and protostomes (including annelids and insects) and the cnidarians (e.g. the sea anemone), which are representatives of more ancient animals. However, the interaction of these genes has been studied in deuterostomes and cnidarians but not in protostomes. Here, we present the first study the function of the gene foxQ2 in protostomes. We found that the gene acts at the top level of the genetic network and when its function is knocked down, the labrum (a part of the head) and higher order brain centers do not develop. This is in contrast to the other animal groups where foxQ2 appears to play a less central role. We conclude that foxQ2 has acquired additional functions in the course of evolution of protostomes.

developmental biology↗