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Researchers 3D print human colon model with bioelectronics

Closely matching its human counterpart, the work from UC Irvine eliminates the need for animal testing

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According to the University of California, Irvine (UC Irvine), researchers have developed a 3D human colon model integrated with bioelectronics to aid in colorectal cancer research and drug discovery. The ‘3D in vivo mimicking human colon’ enables precision and personalized medicine, offering a more ethical, accurate, and cost-effective alternative to traditional animal testing.

In a paper published in the journal Advanced Science, researchers in UC Irvine’s Samueli School of Engineering outline their creation of an approximately 5-by-10-millimeter replica that incorporates essential structural features of a colon, including liminal curvature, multilayered cellular organization, and the spontaneous formation of 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, 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 non-animal models and new approaches that experts at the US Food and Drug Administration are seeking.”

Esfandyar-pour said he was inspired to undertake this project when he noticed critical limitations in current preclinical testing methods to detect and treat colon maladies. He said roughly half of rodent-derived toxicological findings fail to accurately predict human toxicities, and animal models often inadequately capture critical aspects of human tumor biology. Also, animal-based studies require financial resources that often total multiple millions of dollars over a four- to five-year period for routine cancer studies alone.

“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,” said Esfandyar-pour. “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 constructed using a biological scaffold made from gelatin methacrylate mixed with alginate, which together form a support matrix that mimics the colon’s soft tissue. Human colon cells line the inner surface of the mini-colon, while supportive fibroblasts are embedded in the outer layer to re-create the colon’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,” said Esfandyar-pour.

He added that the 3D-IVM-HC model outperforms traditional culture-based drug screening systems. In experiments using the chemotherapy drug 5-fluorouracil, the model showed that cancer cells were much more resistant to treatment – requiring roughly 10 times higher doses to achieve the same cell-killing effect as an application in a conventional petri dish. This mirrors the drug resistance observed in real patient tumors, indicating the model’s higher fidelity for drug testing.

The platform opens new avenues for tailored treatments, according to the paper. Researchers envision taking a patient’s own cells from a tumor biopsy and growing a personalized mini-colon to determine which drug works best for that individual patient.

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