By Topic

Engineering a Biomimetic Villus Array for In Vitro Three-Dimensional Culture of Intestinal Epithelial Cells

Sign In

Cookies must be enabled to login.After enabling cookies , please use refresh or reload or ctrl+f5 on the browser for the login options.

Formats Non-Member Member
$31 $13
Learn how you can qualify for the best price for this item!
Become an IEEE Member or Subscribe to
IEEE Xplore for exclusive pricing!
close button

puzzle piece

IEEE membership options for an individual and IEEE Xplore subscriptions for an organization offer the most affordable access to essential journal articles, conference papers, standards, eBooks, and eLearning courses.

Learn more about:

IEEE membership

IEEE Xplore subscriptions

6 Author(s)
Wen-Cheng Yang ; Inst. of Nano Eng. & Microsyst., Nat. Tsing Hua Univ., Hsinchu, Taiwan ; Yuan-Ching Chen ; Yu-Sheng Huang ; Ya-Yuan Fu
more authors

Small intestinal villi are projective microstructures from the mucosa that provide a large surface area for digestion and absorption. On the mucosa, intestinal epithelial cells undergo terminal differentiation in space-along the crypt-villus axis-until they slough off into the lumen. Despite this unique physiological feature, to date in vitro cultivation of the intestinal epithelial cells is routinely done at the planar tissue-culture surface. In this research, we fabricated a projective, three-dimensional (3-D) tissue-culture environment to provide a physiologically relevant condition for establishing the enterocyte cell culture in vitro. We used the mouse small intestinal epithelium as the model and applied a microfabrication process, UV-LIGA, to generate an array of microneedles with a similar projective structure and size (height: 400 μm, base: 135 μm in diameter) as those of the duodenal villi. In addition, we shaped the LIGA-derived poly (lactic acid) microneedles by acetone/ethanol erosion to create a smooth tip structure for the engraftment of human Caco-2 enterocytes. The engineered villus array had a total surface area of 4.81 cm2 per sq.cm. of planar surface, which led to a 2.48-fold increase in the cell number of enterocytes on the 3-D construct relative to that on the planar control surface. Staining tests of cellular components (nuclei and membranes), viability, and the ZO-1 tight-junction protein show that the projective PLA villus structure, similar to the two-dimensional surface, provided a suitable environment for the Caco-2 culture. This is the first time in UV-LIGA research field to use the 3-D lithography method to generate microstructures mimicking the intestinal structures. In addition, our work presents an initial step toward constituting a physiological gut in vitro by using an engineering approach for large-scale preparation of the biomimetic small intestine.

Published in:

Microelectromechanical Systems, Journal of  (Volume:21 ,  Issue: 6 )