Engineering an In Vitro Silk-Based Intestinal Model Using Topographical Features.
Tse, Megan W.
- Millions of people worldwide are affected by intestinal diseases, which can severely affect people’s quality of lives. Options to study intestinal functions and associated diseases are limited by existing models: cell co-cultures, microfluidic systems, organoid models, animal studies, and other in vitro systems. To replicate the in vivo functions of the intestines, we aimed to recreate the physica... read morel environment of the small intestinal niche through the incorporation of crypt- and villus-like structures in our current 3D tissue engineered intestinal model. With the goal of promoting the self-renewal of the intestinal epithelium, we seeded enteroids on patterned silk scaffolds. We aimed to look at the impact of the topographical features and the 3D geometry of the intestines of the intestinal epithelium formation and maturation. We’ve also used a novel method to create these topographical features through 3D printing, which is more efficient, quicker, and more cost efficient than the standard photolithography. In the further development of the model, we have demonstrated the ability of 3D printing to create villus- and crypt-like features. In addition, the possibility of incorporating these features in silk hydrogel and film coated silk sponges was also pursued. With initial seeding we have demonstrated the possibility of enteroids to adhere and proliferate to the featured silk hydrogel scaffolds and the formation of a polarized epithelial cell layer on the villus-like features. Through future works, we will be able to develop an in vitro physiologically relevant intestinal model that can be used for evaluating treatment cascades and screening orally delivered pharmaceuticals.read less