Stress-relaxing granular bioprinting materials enable complex and uniform organoid self-organization - Nature Materials

A tunable granular biomaterial matrix is developed to support long-term bioprinting. Stress relaxation at high strains and long timescales is shown to be important for tissue self-organization in inte...

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Stress-relaxing granular bioprinting materials enable complex and uniform organoid self-organization - Nature Materials

A tunable granular biomaterial matrix is developed to support long-term bioprinting. Stress relaxation at high strains and long timescales is shown to be important for tissue self-organization in inte...

nature.com

LGBTQ+ realities in the biological sciences

While scientific environments have been described as unwelcoming to the LGBGQ+ community, and fields like physics have systematically documented these challenges, the climate in biology workplaces has...

biorxiv.org

Differential Effects of Confinement on the Dynamics of Normal and Tumor-Derived Pancreatic Ductal Organoids

Pancreatic ductal adenocarcinoma (PDAC) is a cancer of the epithelia comprising the ductal network of the pancreas. During disease progression, PDAC tumors recruit fibroblasts that promote fibrosis, increasing local tissue stiffness and subjecting epithelial cells to increased compressive forces. Previous in vitro studies have documented cytoskeletal and nuclear adaptation following compressive stresses in two-dimensional (2D) and three-dimensional (3D) environments. However, a comparison of the responses of normal and tumor-derived ductal epithelia to physiologically relevant confinement remains underexplored, especially in 3D organoids. Here we control confinement with an engineered 3D microenvironment composed of Matrigel mixed with a low yield stress granular microgel. Normal and tumor-derived murine pancreas organoids (normal and tumor) were cultured for 48 h within this composite 3D environment or in pure Matrigel to investigate the effects of confinement on morphogenesis and lumen expansion. In confinement, tumor organoids (mT) formed a lumen that expanded rapidly, whereas normal organoids (mN) expanded more slowly. Moreover, a majority of normal organoids in more-confined conditions exhibited an inverted apicobasal polarity compared to those in less-confined conditions. Tumor organoids exhibited a collective “pulsing” behavior that increased in confinement. These pulses generated forces sufficient to locally overcome the yield stress of the microgels in the direction of organoid expansion. Normal organoids more commonly exhibit unidirectional rotation. Our in vitro microgel confinement platform enabled the discovery of two distinct modes of collective force generation in organoids that may shed light on the mutual interactions between tumors and the microenvironment. These insights into in vitro dynamics may deepen our understanding of how the confinement of healthy cells within a fibrotic tumor niche disrupts tissue organization and function in vivo.

pubs.acs.org

Engineering kidney developmental trajectory using culture boundary conditions

Kidney explant cultures are traditionally carried out at air-liquid interfaces, which disrupts 3D tissue structure and limits the interpretation of developmental data. To overcome this limitation, we ...

biorxiv.org

MAGIC matrices: freeform bioprinting materials to support complex and reproducible organoid morphogenesis

Organoids are powerful models of tissue physiology, yet their applications remain limited due to their relatively simple morphology and high organoid-to-organoid structural variability. To address the...

biorxiv.org