Microscale 3-D hydrogel scaffold for biomimetic gastrointestinal (GI) tract model

TLDR

Conventional techniques struggle to fabricate soft hydrogels into high‑aspect‑ratio, curved 3‑D geometries. The authors propose a simple, efficient method to create natural and synthetic hydrogels with high aspect ratio and curvature, enabling microscale, physiologically realistic in‑vitro tissue models. The method combines laser ablation with calcium‑alginate sacrificial molding to minimize mold‑separation stress and allow fabrication of complex hydrogel structures without damage. Using this technique, a microscale collagen scaffold mimicking human intestinal villi density and size was fabricated, and Caco‑2 cells cultured on it for three weeks formed finger‑like epithelial structures resembling villi.

Abstract

Here we describe a simple and efficient method for fabricating natural and synthetic hydrogels into 3-D geometries with high aspect ratio and curvature. Fabricating soft hydrogels into such shapes using conventional techniques has been extremely difficult. Combination of laser ablation and sacrificial molding technique using calcium alginate minimizes the stress associated with separating the mold from the hydrogel structure, and therefore allows fabrication of complex structures without damaging them. As a demonstration of this technique, we have fabricated a microscale collagen structure mimicking the actual density and size of human intestinal villi. Colon carcinoma cell line, Caco-2 cells, was seeded onto the structure and cultured for 3 weeks until the whole structure was covered, forming finger-like structures mimicking the intestinal villi covered with epithelial cells. This method will enable construction of in vitro tissue models with physiologically realistic geometries at microscale resolutions.