Biological barriers are the protective structures of our bodies that separate the “inside” from the “outside” with the role to provide the body with a stable environment. Each barrier has its own distinct design and biological structure but common to all is that they comprise several different cell types that strictly control the passage of molecules to avoid the introduction of compounds that could be harmful for us. Whilst this has evolved to benefit us, at the same time it can be a challenge for drug delivery, as all pharmaceuticals have to cross at least one biological barrier before they can work.
The group of drugs that faces the most challenging route of delivery is medication against neurodegenerative diseases, such as Alzheimer’s. These drugs have to cross from the blood capillaries in the brain, which is termed the blood-brain barrier. Neurodegenerative diseases have recently seen a drastic increase and it is estimated that the economic burden to care for this group of patients in Europe lies close to 800 billion EUR annually so there is a tremendous need to identify effective new drug formulations with efficient delivery pathways to improve current treatment strategies.
To study drug delivery across the blood-brain barrier, researchers today rely heavily upon animal models. Such studies give absolute information on the biological processes but they also have a number of limitations. An alternative approach, which allows for fully controlled experiments, is to use cell culture-based models i.e. cells grown under controlled conditions outside of their natural environment. However, these lack the naturally existing chemical and mechanical cues that would be found in ‘real-life’ environments, and do not compare well with the blood-brain barrier.
The overall aim of this project is to build the cell structure in biologically-derived materials that naturally include the necessary biomolecules, using methods that can handle and structure such materials. This will unlock the use of next generation animal-free ‘barrier-on-chip’ models that can be used to speed up drug development, serve as screening platforms for nanotoxicology and help medical researchers to understand how drug delivery works.
- M. Tenje, F. Cantoni, A.M. Porras Hernández, S.S. Searle, S. Johansson, L. Barbe, M. Antfolk and H. Pohlit. A practical guide to microfabrication and patterning of hydrogels for biomimetic cell culture scaffolds, Organs-on-a-chip 2 (2020) 100003 DOI: 10.1016/j.ooc.2020.100003
- F. Cantoni, G. Werr, L. Barbe, A.M. Porras Hernández, M. Tenje. A microfluidic chip carrier including temperature control and perfusion system for long-term cell imaging. HardwareX 10 (2021) e00245 DOI: 10.1016/j.ohx.2021.e0024
- A.M. Porras Hernández, L. Barbe, H. Pohlit, M. Tenje and M. Antfolk. Confocal imaging dataset to assess endothelial cell orientation during extreme glucose conditions. Sci. Data 9, 26 (2022) DOI: 10.1038/s41597-022-01130-x
We gratefully acknowledge funding from the European Research Council under grant agreement no. 757444
Duration: 01 Jan 2018 - 31 Dec 2022