Researchers at the University of California, Irvine have developed a 3D human colon model that incorporates bioelectronics, designed to improve colorectal cancer research and drug discovery. The new model, called the “3D in vivo mimicking human colon,” aims to provide a more ethical and accurate alternative to animal testing by closely replicating the structure and function of the human colon.
The model is described in a recent publication in Advanced Science by researchers from UC Irvine’s Samueli School of Engineering. It measures about 5 by 10 millimeters and includes features such as curvature, multilayered cellular organization, and cryptlike indentations similar to those found in human tissue.
“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.”
Esfandyar-pour noted that current preclinical testing methods using animals often fail to predict human responses accurately. He stated that about half of toxicological findings from rodent studies do not match human outcomes, and animal models often miss key aspects of human tumor biology. Additionally, he highlighted the high financial costs associated with animal-based studies.
“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 artificial colon is constructed from a scaffold made of gelatin methacrylate mixed with alginate to mimic soft tissue. Human colon cells line its inner surface while fibroblasts in the outer layer recreate the living environment of the colon.
“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 said.
Experiments using chemotherapy drug 5-fluorouracil showed that cancer cells grown in this model were much more resistant to treatment compared to those in traditional petri dishes. The required dose was roughly ten times higher to achieve similar effects, which aligns with resistance patterns seen in real patient tumors.
Researchers believe this platform could be used for personalized medicine by growing mini-colons from individual patients’ tumor cells to identify effective treatments on a case-by-case basis.
The development process for the model takes about two weeks for cultivation and maturation, followed by several days of testing—significantly faster than traditional animal studies.
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. This research may represent a significant step toward global efforts to develop more reliable, humane and cost-effective alternatives to animal testing, potentially advancing precision medicine and improving outcomes for patients with colorectal cancer worldwide.”
Other contributors included researchers from UC Irvine’s Departments of Biomedical Engineering; Electrical Engineering and Computer Science; Chemical and Biomolecular Engineering; as well as collaborators from New York Institute of Technology. The project was funded by UC Irvine’s Samueli School of Engineering.
UC Irvine was founded in 1965 and is recognized as one of the top public universities in the United States. The university enrolls over 36,000 students across 224 degree programs. More information can be found at www.uci.edu.
