UC Irvine Team Creates 3D In Vivo–Mimicking Human Colon to Advance Cancer Drug Discovery

Date:2025-10-27 11:26:35

Researchers at the U.S.-based University of California, Irvine have developed a 3D human colon model integrated with bioelectronics to advance colorectal cancer research and drug discovery. The 3D in vivo–mimicking human colon is designed to enhance precision and personalized medicine while reducing reliance on animal testing, offering a more ethical, accurate, and cost-effective alternative.

In a study published in Advanced Science, UC Irvine’s Samueli School of Engineering team detailed their development of a 5-by-10-millimeter colon replica that reproduces key anatomical features such as curvature, multilayered cellular structures, and cryptlike indentations.

“The three-dimensional shapes, curves and crypts in our 3D-IVM-HC model are central to maintaining more realistic cell behavior even at a scaled-down size,” said senior author Rahim Esfandyar-pour, assistant professor of electrical engineering and computer science at UC Irvine. “And because our model more closely reproduces human colon biology, it could potentially be used to screen drugs or test treatments in a way that better predicts patient responses than animal models or simple cell cultures. It could be among the strong nonanimal models and new approaches that experts at the U.S. Food and Drug Administration are seeking.”

Addressing Limitations of Animal Testing

Esfandyar-pour explained that the project stemmed from recognizing limitations in preclinical testing for colon diseases. He noted that nearly half of toxicology findings from rodent studies fail to accurately predict human responses, while animal models often overlook critical aspects of human tumor biology. These studies are also costly, often reaching millions of dollars over several years.

“Our bioelectronic-integrated 3D-IVM-HC model addresses some of the practical and ethical challenges in animal-based research, offering a human cell-based, animal-free approach with the potential to enable rapid, cost-effective and scalable translational studies,” Esfandyar-pour said. “By eliminating interspecies variability, the model has the ability to enhance clinical translatability, providing an accelerated and ethically responsible pathway for preclinical research.”

The model is built using a gelatin methacrylate and alginate scaffold that mimics the colon’s soft tissue. Human colon cells line its inner surface, while fibroblasts embedded in the outer layer help re-create the organ’s living environment. “This intricate architectural arrangement promotes robust cell-to-cell interactions, yielding a fourfold increase in cell density relative to conventional 2D cultures and possibly enhancing physiological relevance and barrier function,” Esfandyar-pour explained.

Applications in Drug Testing and Personalized Medicine

Testing with the chemotherapy drug 5-fluorouracil revealed that cancer cells in the model showed higher drug resistance—requiring nearly 10 times more dosage to achieve the same effect as in traditional petri dish cultures. This outcome mirrors the resistance observed in actual patient tumors, suggesting greater accuracy for preclinical drug screening.

The model also enables patient-specific applications. Researchers envision growing personalized mini-colons from biopsy samples to evaluate which treatments work best for individual patients. The entire process—two weeks for cultivation and a few days for testing—offers a faster, lower-cost alternative to animal research while maintaining physiological realism.

Esfandyar-pour added, “Hospitals and laboratories could ultimately use such models to run preclinical tests on new therapies in an ethical, timely manner, possibly transforming the drug development pipeline.” He noted that this work could improve predictive accuracy, advance mechanistic understanding, and speed up precision drug discovery.

3D Printed Personalized Medicines: The Future of Healthcare

University of California is well-positioned within the larger trend toward individualized treatments in the pharmaceutical industry. In 2023, the company advanced personalized on-demand treatments with its MED-U Modular 3D printer. In collaboration with institutions like the University Hospital Center of Nîmes, MB Therapeutics is developing tailored medication solutions, particularly for pediatric patients. This approach helps reduce dosing errors and improves the quality of life for both patients and families.

Another example of this trend is UK-based biotech company FabRx, which is exploring 3D printing for the automation of capsule filling in community pharmacies. Their 2025 study seeks to address the inefficiencies and potential for human error in manual compounding. Using semi-solid extrusion (SSE) technology, FabRx’s 3D printers provide more accurate dosing and greater consistency.

Elsewhere, researchers at the Max Planck Institute for Informatics and the University of California, Davis, have developed a 3D printing process to create pills in specific shapes to control drug release rates. This technology offers new possibilities for more precise drug delivery, providing significant advantages over traditional methods.

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