title: 3-D intestinal scaffolds for evaluating the therapeutic potential of probiotics.
abstract: Biomimetic in vitro intestinal models are becoming useful tools for studying host-microbial interactions. In the past, these models have typically been limited to simple cultures on 2-D scaffolds or Transwell inserts, but it is widely understood that epithelial cells cultured in 3-D environments exhibit different phenotypes that are more reflective of native tissue, and that different microbial species will preferentially adhere to select locations along the intestinal villi. We used a synthetic 3-D tissue scaffold with villous features that could support the coculture of epithelial cell types with select bacterial populations. Our end goal was to establish microbial niches along the crypt-villus axis in order to mimic the natural microenvironment of the small intestine, which could potentially provide new insights into microbe-induced intestinal disorders, as well as enabling targeted probiotic therapies. We recreated the surface topography of the small intestine by fabricating a biodegradable and biocompatible villous scaffold using poly lactic-glycolic acid to enable the culture of Caco-2 with differentiation along the crypt-villus axis in a similar manner to native intestines. This was then used as a platform to mimic the adhesion and invasion profiles of both Salmonella and Pseudomonas, and assess the therapeutic potential of Lactobacillus and commensal Escherichia coli in a 3-D setting. We found that, in a 3-D environment, Lactobacillus is more successful at displacing pathogens, whereas Nissle is more effective at inhibiting pathogen adhesion.
authors.affiliation: Department of Biological and Environmental Engineering, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Cait M
authors.initials: CM
authors.lastname: Costello
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Sorna
authors.forename: Yih-Lin
authors.initials: YL
authors.lastname: Goh
authors.forename: Ivana
authors.initials: I
authors.lastname: Cengic
authors.forename: Nina K
authors.initials: NK
authors.lastname: Jain
authors.forename: John C
authors.initials: JC
authors.lastname: March
mesh_terms: D001419:Bacteria / Q000187:drug effects; D001422:Bacterial Adhesion / Q000187:drug effects; D032701:Biomimetics / Q000379:methods; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D004341:Drug Evaluation / Q000379:methods*; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects* / Q000382:microbiology; D019936:Probiotics / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000382:microbiology