bioRxiv Science⌕ Search

Biology subjects

Pietrzak, K.

Publications and source records attributed to Pietrzak, K..

2 recordsLinked to original sources

Controlling Flow Dynamics and Permeability in Perfusable Vascular Constructs Using Volumetric 3D Printing

Creating perfusable vascular networks that replicate physiological flow remains a key challenge in tissue engineering. Here, we present a volumetric 3D printing (Vol3DP) method for fabricating tunable, biologically relevant vascular structures that enable controlled perfusion. A recyclable resin of methacrylated gelatin (GelMA) and polyethylene glycol diacrylate (PEGDA) was optimized for Vol3DP to produce high-fidelity hydrogels with embedded channels. To evaluate the relationships between flow, structure, and function, we designed modular perfusion platforms that offer precise control over physiological shear stress (3-50 dyne/cm{superscript 2}), flow rates (1-15 mL/min), and flow modes, including pulsatile and continuous. These platforms support endothelial cell attachment and spreading under static seeding conditions, sustained perfusion, and permeability assessment and further allow for direct comparisons of flow dynamics and perfusion efficiency in channel-in-hydrogel systems. The finally engineered adaptable platform allowed for independent pressure modulation within the vessel and the outside environment. We conducted simulations of flow and hydrogel permeability that closely resemble experimental results. These results underscore the dominance of diffusive transport through the hydrogel matrix and highlight the ability of our system to simulate physiologically relevant mass transfer phenomena. Finally, we conducted a pilot study using Galleria mellonella larvae to compare active and passive dye transport in vivo, complementing in vitro data and highlighting the importance of perfusion-capable scaffolds for accurately simulating vascular drug delivery environments. O_FIG O_LINKSMALLFIG WIDTH=172 HEIGHT=200 SRC="FIGDIR/small/669590v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@1add089org.highwire.dtl.DTLVardef@56057forg.highwire.dtl.DTLVardef@182e989org.highwire.dtl.DTLVardef@1b235a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

BAZ2A association with H3K14ac is required for the dedifferentiation of prostate cancer cells into a cancer stem-like state

Prostate cancer (PCa) is one of the most prevalent cancers in men. Cancer stem cells are thought to be associated with PCa relapse. Here we show that BAZ2A is required for the transition of PCa cells into a cancer stem-like state. BAZ2A genomic occupancy in PCa cells coincides with H3K14ac enriched chromatin regions. This association is mediated by BAZ2A-bromodomain (BAZ2A-BRD) that specifically binds H3K14ac. BAZ2A associates with inactive enhancers marked by H3K14ac and repressing transcription of genes frequently silenced in aggressive and poorly differentiated PCa. BAZ2A-mediated repression is also linked to EP300 that acetylates H3K14ac. BAZ2A-BRD mutations or treatment with inhibitors abrogating BAZ2A-BRD/H3K14ac interaction impair the transition of PCa cells into a stem-like state. Furthermore, pharmacological inactivation of BAZ2A-BRD impairs Pten-loss oncogenic transformation of prostate organoids. Our findings indicate a role of BAZ2A-BRD in PCa stem cell features and suggest potential epigenetic-reader therapeutic strategies to target BAZ2A in aggressive PCa.

molecular biology↗