02359nas a2200277   4500000000100000000000100001008004100002653002500043653003100068653002200099653002100121100003400142700002400176700002100200700002200221700001800243700001900261700002000280700002400300245011300324856006700437300001100504490000800515520154400523022001402067                                       d10a3D colon human model10acolorectal cancer modeling10ain vivo mimicking10anon-animal model1 aJorge Alfonso Tavares-Negrete1 aSahar Najafikoshnoo1 aAnita Ghandehari1 aMozhgan Keshavarz1 aQuinton Smith1 aArmand Ahmetaj1 aSteven Zanganeh1 aRahim Esfandyarpour00aDevelopment of a 3D Human Colon Model Along with Bioelectronics for the Induction and Monitoring of Diseases  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202506377  ae063770 vn/a3 aConventional 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 cm2, 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 (IC5₀) of 540 ± 30 µm, an order of magnitude higher than a matched two-dimensional (2D) monolayer (42 ± 5 µm), 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.  a2198-3844