Mini colon from 3D printing: UC Irvine combines tissue model with bioelectronics

A research team at the University of California, Irvine presents a 3D model of the human colon that reproduces structural features of the organ and can be combined with bioelectronics. The “3D in vivo mimicking human colon” (3D-IVM-HC) aims to enable more precise preclinical tests for colorectal tumors and personalized drug screening. The work appeared in Advanced Science and addresses the gap between simple cell cultures and elaborate animal experiments.

Technically, the replica is based on a hydrogel scaffold of gelatin methacrylate and alginate, which serves as a soft support matrix. Epithelial cells line the inside of the lumen, while fibroblasts are embedded in the outer layer to mimic the stromal environment. In culture, curved lumen segments, multilayered cell assemblies, and crypt-like depressions emerge, which are relevant for barrier function and physiological responses to drugs.

“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 Esfandyarpour, UC Irvine assistant professor of electrical engineering and computer science. “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.”

“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,” Esfandyarpour said. “By eliminating interspecies variability, the model has the ability to enhance clinical translatability, providing an accelerated and ethically responsible pathway for preclinical research.”

In pharmacological tests, the model showed more pronounced drug resistance than 2D cultures: for 5-fluorouracil, doses about ten times higher were required to achieve comparable cytotoxicity. According to the authors, this reflects the more robust physiology of patient tumors and improves the informativeness of dose–response curves.

“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,” Esfandyarpour said.

“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 said. “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.”

In the long term, the researchers outline patient-specific applications: biopsy material could be used to culture an individual mini-colon to compare drug candidates and dosages. For clinical transfer, validation, standardization of measurement methods, and scaling remain crucial. If successful, the system could measurably accelerate the preclinical workflow for colorectal cancer drugs and replace animal testing for selected questions.