Journal article
Dual-Material 3D-Printed Intestinal Model Devices with Integrated Villi-like Scaffolds
Department of Health Technology, Technical University of Denmark1
Biomimetics, Department of Health Technology, Technical University of Denmark2
Polymer Cell, Biomimetics, Department of Health Technology, Technical University of Denmark3
Colloids & Biological Interfaces, Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark4
Biologically Inspired Material Engineering, Biomimetics, Department of Health Technology, Technical University of Denmark5
Bio-observatory, Biomimetics, Department of Health Technology, Technical University of Denmark6
Digital Health, Department of Health Technology, Technical University of Denmark7
Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark8
In vitro small intestinal models aim to mimic the in vivo intestinal function and structure, including the villi architecture of the native tissue. Accurate models in a scalable format are in great demand to advance, for example, the development of orally administered pharmaceutical products. Widely used planar intestinal cell monolayers for compound screening applications fail to recapitulate the three-dimensional (3D) microstructural characteristics of the intestinal villi arrays.
This study employs stereolithographic 3D printing to manufacture biocompatible hydrogel-based scaffolds with villi-like micropillar arrays of tunable dimensions in poly(ethylene glycol) diacrylates (PEGDAs). The resulting 3D-printed microstructures are demonstrated to support a month-long culture and induce apicobasal polarization of Caco-2 epithelial cell layers along the villus axis, similar to the native intestinal microenvironment.
Transport analysis requires confinement of compound transport to the epithelial cell layer within a compound diffusion-closed reservoir compartment. We meet this challenge by sequential printing of PEGDAs of different molecular weights into a monolithic device, where a diffusion-open villus-structured hydrogel bottom supports the cell culture and mass transport within the confines of a diffusion-closed solid wall.
As a functional demonstrator of this scalable dual-material 3D micromanufacturing technology, we show that Caco-2 cells seeded in villi-wells form a tight epithelial barrier covering the villi-like micropillars and that compound-induced challenges to the barrier integrity can be monitored by standard high-throughput analysis tools (fluorescent tracer diffusion and transepithelial electrical resistance).
Language: | English |
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Publisher: | American Chemical Society |
Year: | 2021 |
Pages: | 58434-58446 |
ISSN: | 19448252 and 19448244 |
Types: | Journal article |
DOI: | 10.1021/acsami.1c22185 |
ORCIDs: | Dolatshahi-Pirouz, Alireza , Larsen, Niels B. , Taebnia, Nayere , Kromann, Emil B and Andresen, Thomas L |
3D tissue models Hydrogels Intestinal barrier Multi-material 3D printing Stereolithography Villi
Biocompatible Materials Caco-2 Cells Cells, Cultured Humans Intestine, Small Materials Testing Models, Biological Polyethylene Glycols Printing, Three-Dimensional Tissue Scaffolds hydrogels intestinal barrier multi-material 3D printing multi-material 3Dprinting stereolithography villi