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

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.

Use of Collagen Gel as an Alternative Extracellular Matrix for the In Vitro and In Vivo Growth of Murine Small Intestinal Epithelium

“…31 Several groups have reported the capacity to grow Caco-2 cells using collagen gel. [32][33][34] The results reported herein are novel. They are the first demonstration of the long-term in vitro growth of nontransformed small intestinal crypts using a completely defined cell culture system, to which the addition of ISEMF allows for in vivo applications.…”

A living system on a chip

“…The intestines, a barrier that must be passed by all swallowed drugs, seem surprisingly easy to model (see 'Just cells'): using cell lines representing only the gut epithelium, mucin-secreting cells and lymphocytes, Shuler and his colleagues have been able to recreate the mucoid layer in the gut 5 . With the help of an absorbent polymer gel that can be used to build microscale scaffolding, the team has even crafted a collagen structure to represent the villi that line the intestinal wall 6 . Meanwhile, the Wyss team is developing a model of the gut that mimics peristalsis using vacuum chambers similar to those in the lung chip.…”

Integrating biological vasculature into a multi-organ-chip microsystem

“…[1][2][3][4][5] Moreover, the success in individual tissue culture microsystems has stimulated researchers to challenge a more systemic level of human biology in vitro through so-called ''body-on-a-chip'' or ''human-on-a-chip'' systems. [6][7][8][9] Such systems aim to combine several organ equivalents within a human-like metabolizing environment or aim at in vivo-like pharmacokinetics and pharmacodynamics.…”