A Tri-Cell Culture Model of Human Intestine Constructed on Electrospun Polyurethane Scaffold Inserts in the MIVO^® Millifluidic Device: Effect of Static vs. Dynamic Flow Culture Conditions

Accurate in vitro modelling of the human gut is a key need for drug development and disease treatment.
However, traditional in vitro models struggle to accurately replicate the gut’s complex mechanisms. The aim of the current work is to develop an in vitro model that more accurately reproduces the morphological and functional aspects of the human intestinal epithelium, including incorporation of dynamic in vivo-like basolateral perfusion to mimic interstitial fluid flow and peristaltic mechanical forces.

We developed a novel in vitro human intestinal model using a tri-culture system of enterocyte- and goblet-like epithelial cells with human dermal fibroblasts, cultured on flexible Bio-Spun^® PU scaffolds within the MIVO^® millifluidic organ-on-chip device.

The flexible scaffolds provide superior tissue attachment compared to traditional rigid membranes, preventing culture detachment and supporting multilayered epithelial structures. Under dynamic medium flow, the model exhibits enhanced epithelial differentiation, increased goblet and Paneth cell-like morphology, and improved barrier function as measured by TEER and FITC-dextran permeation.

This approach offers a more predictive and physiologically relevant platform for drug absorption, permeability, and intestinal physiology studies, highlighting the advantages of combining flexible Bio-Spun^® PU scaffolds with dynamic flow in organ-on-chip systems.

• • • • • Conference: SOT 2026, San Diego
        • Authors: E. Palamà¹, M. Aiello¹, S. Scaglione¹, P. Hayden², M.D. Phaneuf²