TY - JOUR
KW - 3D colon human model
KW - colorectal cancer modeling
KW - in vivo mimicking
KW - non-animal model
AU - Jorge Alfonso Tavares-Negrete
AU - Sahar Najafikoshnoo
AU - Anita Ghandehari
AU - Mozhgan Keshavarz
AU - Quinton Smith
AU - Armand Ahmetaj
AU - Steven Zanganeh
AU - Rahim Esfandyarpour
AB - 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 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.
BT - Advanced Science
DO - 10.1002/advs.202506377
IS - n/a
LA - en
N2 - 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 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.
EP - e06377
T2 - Advanced Science
TI - Development of a 3D Human Colon Model Along with Bioelectronics for the Induction and Monitoring of Diseases
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202506377
VL - n/a
Y2 - 2025-10-28
SN - 2198-3844
ER -