On Friday 30 July, Nayere Taebnia will defend her PhD thesis: “3D Printed Human Small Intestine Models for Drug Delivery Testing and Disease Modelling”.
Time: Friday 30 July, at 14:00
Place: Building 341, aud. 22
Important: Active registration:
- Building 341, aud. 22
Due to Covid-19 there is a restriction on the number of participants who are physically present in aud. 22.
Therefore, if you wish to be present in the auditorium, please sign up here:
https://www.conferencemanager.dk/phdnayere/signup
All participants present in aud. 22 are responsible for complying with the applicable guidelines for distance, valid corona pas etc.
- Zoom sign up:
https://dtudk.zoom.us/meeting/register/u5ctde2srTwiGdB_1MIVP31VdVogrgpYkB30
Please be aware that the PhD defence may be recorded - This will also be informed at the beginning of the PhD defence.
Supervisors:
Principal supervisor: Professor Thomas L. Andresen
Co-supervisor: Professor Niels B. Larsen
Examiners:
Associate Professor Martin Dufva, DTU Health Tech
Professor Linda G. Griffith, Massachusetts Institute of Technology
Research Director Laurent Malaquin, LAAS CNRS
Chairperson at defence:
Associate Professor Leticia Hosta-Rigau
Abstract:
Among various drug administration routes, oral delivery is the most desirable and convenient approach. Orally administered drugs are mainly absorbed in the small intestine and therefore, in vitro intestinal models, as a cheaper and more ethical alternative to animal models, are of particular interest for studying drug uptake and assessing toxicity in the screening phase and preclinical development. Heretofore, in vitro intestinal models have been restricted to two-dimensional (2D) monolayer of a human colorectal carcinoma cell line, Caco-2 cells, cultured on standard microporous membranes which allow for diffusive transport. While these 2D models initially provided important biological insights, they lack the complex 3D geometry of the small intestine, namely the crypt-villus, and that results in limited prediction ability of such models when it comes to the drug performance. The main focus of the present thesis was to address the limitations of conventional models by establishing more physiologically accurate, diffusion-open and mechanically stable in vitro intestinal models by taking advantage of projection stereolithographic 3D printing (SLA). We reported the fabrication of multi-material SLA printed static and microfluidic models which encompass the villi-like microstructures of the small intestine. To this end, poly(ethylene glycol) diacrylate (PEGDA) of varied molecular weight was utilized as the main component of the printing resin. To promote the cell adhesion, a small amount of GelMA was incorporated into the hydrogel network and the scaffolds were coated with extracellular matrix proteins. The models were classified in the order of increased physiological relevance and complexity, and enabled quantitative characterization of barrier integrity in a reproducible and high-throughput manner. Our 3D printed models restrict the transport and confine the diffusion through the cellular barrier and enable live imaging thanks to the optical transparency of the material. Consequently, they serve as more physiologically-correct platforms to develop intestinal barrier models for preclinical assessment of new drugs, and to provide mechanistic understanding of the drug transport and absorption through the intestinal barrier.