Researchers at the Institute of Biomedical Engineering at NUST MISIS have developed a prototype porous polymer membrane with a microrelief that mimics the folded surface of the intestine. Based on this membrane, they created an intestinal barrier model whose permeability is 100 times closer to that of human small-intestinal tissue than that of a standard laboratory model. The technology could ultimately improve the accuracy of preclinical drug testing.
Every year, up to 90% of drugs that show promising results in vitro and in animal studies later prove ineffective in humans. One reason for this discrepancy is species differences, as well as limitations of existing preclinical models, which do not reliably predict how the human body will respond. Unreliable preclinical models account for up to 75% of all spending on new drug development.
Permeability is the ability of a barrier to allow substances to pass through it. In the intestine, permeability determines how drugs and nutrients move from the intestinal lumen into the bloodstream. To measure it, a marker substance is passed through a membrane, and researchers record how much of it reaches the other side and how long the process takes. The closer this value is to that of actual human tissue, the more reliable the model is considered to be.
“The standard for studying the intestinal barrier in vitro remains Caco-2 cells cultured on Transwell inserts. This system consists of a flat monolayer that lacks the characteristic ‘villus-crypt’ relief of the intestinal mucosa. The resulting barrier is also three times denser than human intestinal tissue, which significantly reduces its permeability to soluble substances,” Elizaveta Kudan, DSc in Biology and professor at the College of Biomedical Engineering at NUST MISIS.
To address this issue, researchers at NUST MISIS developed a method for producing membranes from polycaprolactone, a biocompatible polymer already used in medicine. The scientists demonstrated that the permeability of the new membrane is two orders of magnitude closer to that of actual human tissue than the standard laboratory model.
“We were able to create a membrane with a stable microrelief that does not flatten out. It is precisely the combination of its structure and carefully selected porosity that allows us to grow intestinal epithelial cells on its surface. These cells form a living barrier that can mimic both healthy intestinal mucosa and disease models. To ensure that the cells were distributed evenly across the complex surface, we additionally treated it with chitosan and polyglutamic acid,” Valentina Kostenko, a co-author of the study and graduate of the iPhD Biomaterials Science program at NUST MISIS.
According to NUST MISIS Rector Alevtina Chernikova, researchers at the university have been conducting biomedical research for several years as part of the strategic technology project “Biomedical Engineering and Biomaterials,” implemented under the national Priority 2030 program. Their work is aimed at developing technologies that can significantly improve people’s quality of life.
A patent application has already been filed for the method of producing the biomimetic membrane.
