Work

Development of a 3D Human Colon Model Along with Bioelectronics for the Induction and Monitoring of Diseases

Year: 2025

Type: article

Abstract: Conventional in vitro and animal models do not reproduce the geometry, mechanics, or transport physics of the human colon, limiting their fidelity for disease studies and drug screening. A patient‐derived, freeform reversible embedding of suspended hydrogels bioprinted three‐dimensional (3D) in vivo mimicking human‐colon model (3D‐IVM‐HC) is reported whose micro‐computed tomography (CT) profile deviates by less than 4% from the original computed tomography template and spontaneously forms crypt‐like invaginations with a median depth of 65 µm. The dual‐layer gelatin methacrylate (GelMA)/alginate matrix matches native colonic stiffness (9–65 kPa) and sustains >95% cell viability with a 14‐fold metabolic increase over 14 days. Caco‐2 epithelia polarize within the lumen, form continuous Zonula occludens‐1 (ZO‐1) belts, and reach a transepithelial electrical resistance (TEER) of 68 ± 4 Ω cm 2 , values within the human ex vivo range. Finite‐element simulations (FEM) parameterized with measured geometry and resistance predict water and nutrient fluxes within 80–99% of human explants. When HCT116 tumor spheroids are introduced, the construct yields a 5‐fluorouracil (5‐FU) half‐maximal inhibitory concentration (IC 5 ₀) of 540 ± 30 µ m , an order of magnitude higher than a matched two‐dimensional (2D) monolayer (42 ± 5 µ m ), mirroring clinical chemoresistance. Together, these benchmarks establish the 3D‐IVM‐HC as a physiologically faithful, non‐animal model for probing colorectal biology and quantifying drug response.

Source: Advanced Science

DOI: 10.1002/advs.202506377