Recreating the Gut:
Advancing Intestinal Architecture with DLP Bioprinting
For decades, researchers relied on 2flat Caco-2 cultures to study intestinal health, but these models miss the crypt-villus architecture that drives nutrient absorption and mucus protection. UC Irvine’s team leveraged DLP bioprinting to recreate these structures, enabling more physiologically relevant gut-mimetic systems.
Prof. Quinton Smith and his team at UC Irvine used CELLINK’s BIONOVA X DLP bioprinter to fabricate GelMA-based constructs with precise geometric confinement and tuned stiffness (~12.5 kPa), creating a physiologically relevant environment for Caco-2 cells. This approach allowed them to induce crypt-villus-like morphogenesis without relying on complex chemical cues, paving the way for more accurate intestinal models.
Studying the small intestine with Caco-2 cells
What is the small intestine?
The inner surface of the human small intestine can span up to 300 m² − about the size of a tennis court. This remarkable area is achieved through finger-like structures called crypt-villi, which enable nutrient absorption and maintain homeostasis. At the base of each crypt, Paneth cells release growth factors that drive cell renewal as cells migrate upward, eventually dying and being replaced. This cycle supports intestinal health and mucus production, forming a protective layer across the intestinal surface.
Why tradional models fall short
Leveraging DLP Bioprinting for gut-mimetic systems
Dr. Nate Bumas, lead author of Geometrically Controlled WNT Activation Drives Intestinal Morphogenesis (2025).
To overcome these limitations, Prof. Quinton Smith and his team at UC Irvine used CELLINK’s BIONOVA X DLP bioprinter to fabricate GelMA-based constructs with precise geometric confinement and tuned stiffness (~12.5 kPa), creating a physiologically relevant environment for Caco-2 cells.
This approach allowed them to induce crypt-villus-like morphogenesis without relying on complex chemical cues, paving the way for more accurate intestinal models.
Geometry and stiffness: Drivers of morphogenesis
The team hypothesized that shape and stiffness together could trigger WNT signaling and promote crypt-villus-like structures. To test this, they used the BIONOVA X to print microwells in various shapes, including triangles, circles, and stars, with controlled sizes and depths. Smaller, confined shapes significantly increased MUC2 expression, a key marker of intestinal function, compared to larger shapes or flat surfaces. When treated with blebbistatin, a drug that reduces cell contractility, these effects disappeared, proving that cytoskeletal tension and confinement drive crypt-villus-like morphogenesis.
Why Bioprinting Was Essential
The team hypothesized that shape and stiffness together could trigger WNT signaling and promote crypt-villus-like structures. To test this, they used the BIONOVA X to print microwells in various shapes, including triangles, circles, and stars, with controlled sizes and depths. Smaller, confined shapes significantly increased MUC2 expression, a key marker of intestinal function, compared to larger shapes or flat surfaces. When treated with blebbistatin, a drug that reduces cell contractility, these effects disappeared, proving that cytoskeletal tension and confinement drive crypt-villus-like morphogenesis.
– Professor Quinton Smith, UC Irvine
Collaboration with CELLINK
Impact and Future Outlook
This work shows that physical cues like confinement and stiffness can activate key signaling pathways, enhancing mucin expression and crypt-villus architecture.
Looking ahead, Smith’s team aims to explore multi-material bioprinting to replicate complex extracellular environments, bringing researchers closer to building multi-cellular tissues like liver lobules and vascularized organs.
Learn more
Publications: Burmas, N. C., Fabian, A. M., Vanavadiya, A., & Smith, Q. (2025). Geometrically Controlled WNT Activation Drives Intestinal Morphogenesis. Advanced Healthcare Materials, 14(23), e2502832. https://doi.org/10.1002/adhm.202502832
