The production of complex, multicellular tissues such as skin or blood vessels can now be envisaged, thanks to the development of a bioreactor with a "decoy effect", by scientists in the "Ingénierie des matériaux polymères" Unit(1) (CNRS / University of Lyon 1/ University of Saint-Etienne / Insa Lyon). This novel, patented bioreactor enabling the culture and co-culture of cells of different types is a world first. The team's work was published in Nature on March 6, 2008.
Living materials can be considered as complex physical hydrogels. This means that they are mainly made up of a network of polymer chains imprisoning a very high proportion of water (80% of net weight, for example, in joint cartilage) and living cells which generate this polymer network. Furthermore, many living tissues comprise several layers of gels containing different cells, and the latter cannot move freely within a layer, and still less from one layer to another.
Using this observation as their starting point, a team in the "Ingénierie des matériaux polymères" Unit, IMP, (CNRS /University of Lyon 1/ University of Saint-Etienne/ Insa Lyon) has developed novel, physical, multi-membrane hydrogels that act as "decoys" for biological media. These biomaterials can adopt many different shapes (spheres, disks, tubes, etc.) and may have numerous biomedical applications. They could be used directly as implants, but also constitute new-generation bioreactors because of their multi-membrane structure.
Unlike those commonly used at present, these new materials enable the cultivation of different cell types in several inter-membrane spaces, so that the production of complex, multi-cellular and multilayer tissues – such as skin or blood vessels – can be envisaged. The "decoy" effect means that advantage can be drawn from the specific biological activity of hydrogels, as the membrane degradation process can be slowed down. Indeed, when membranes are only made up of the "bricks" present in mammalian tissues, cells in the latter recognize the entire biomaterial and produce enzymes to destroy it rapidly and prematurely.
This then leads to the inter-penetration of cells that were initially compartmentalized, which is detrimental to the construction of complex multilayer and multi-cellular tissues such as skin. However, if membranes are endowed with entities that are absent in mammals, their biodegradation will be markedly slower, thus enabling separation of the culture of cells of different types but not preventing their communication. This innovative bioreactor has recently been patented.
Collaboration with cell biology specialists(2) has already made it possible to prove the efficacy of these new bioreactors. Indeed, the biologists cultivated chondrocytes (cartilage cells) in several successive intermembrane spaces for eight months. The results were excellent: the chondrocytes proliferated without becoming transformed into fibroblasts(3) and produced a large quantity of tissue that was very similar to cartilage. The early results of studies on the co-culture of endothelial cells(4) and osteoprogenitor cells(5) have also been very promising, and it is likely that bone tissues could be generated in vitro. In any case, the cells or tissues thus formed remained clearly compartmentalized between the membranes. These bioreactors may therefore be able to respond to the increasing need for graft materials.
1. A. Domard, L. David, S. Ladet. M.T. Corvol, laboratoire Pharmacologie, toxicologie et signalisation cellulaire (Université Paris 5 / Inserm) and L. Bordenave, laboratoire Biomatériaux et réparation tissulaire (Inserm / Université Bordeaux 2.).
3. Cells present in the dermis.
4. Endothelial cells cover the surfaces of all blood vessels. They are thus strategically positioned to influence blood flow and the development of new vessels.
5. Osteoprogenitor cells are cells that enable the generation of bone tissue.
Journal reference: Multi-membrane hydrogels, Sébastien Ladet, Laurent David, Alain Domard, Nature, March 6 2008.
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