Using engineered tissue to energise biohybrid robotics
A thin cellular layer called the epithelia covers every surface of our body, both internally and externally. Examples of epithelial tissue include the outer layer of our skin (the epidermis), the lining of our abdominal cavity, and our sweat glands. “A good example is the lining of our gut, which needs to absorb nutrients and fluids,” says EpiFold project coordinator Xavier Trepat(opens in new window) from the Institute for Bioengineering of Catalonia(opens in new window) in Spain. “Epithelial tissue acts as a barrier, but on top of that, it is highly specific and highly functional.” This functionality is determined by the three-dimensional (3D) shape of the tissue. How processes such as deformation, growth and remodelling combine to create functional 3D structures however is still largely unknown. This is something that the EpiFold project, supported by the European Research Council(opens in new window), sought to address. Furthermore, through uncovering the processes that modulate the shape and mechanics of epithelial tissue, the project team also wanted to open the door to the creation of next-generation biohybrid robots. These could one day have applications in fields such as healthcare.
Understanding epithelial tissue behaviour
“We began by developing technology to measure and manipulate the mechanics of these layers,” explains Trepat. “We wanted to better understand the behaviour of epithelial tissue, especially in the lining of the gut.” To achieve this, organoids – 3D tissue cultures derived from stem cells – were used to study how epithelia adopt 3D shapes. Cutting-edge technologies including micropatterning, microfluidics, optogenetics and mechanical engineering were applied to better understand the behaviour of epithelial tissue. “We also wanted to see if we could use these dynamic cells to build engineering components,” adds Trepat. “Cells have properties that inert materials do not have, such as self-repair and self-powering.”
Division, migration and physiological function change
The project was able to pioneer new technologies to measure the behaviour of these cells. “The gut is in a constant state of self-renewal,” explains Trepat. “The entire surface of our intestine is renewed every week, thanks to cells that divide and migrate, change their physiological function, and eventually die. It is a very dynamic environment.” The EpiFold project shone new light on exactly how this process works, and how the surface of our gut self-renews. “We now better understand the physical forces involved,” remarks Trepat. “We can visualise these processes in vitro, using our organoid combined with our measurement technologies.” Organoid experiments have also shown that metastatic recurrence in colorectal cancer(opens in new window) arises from residual EMP1+ cells found in epithelial tissue. This builds on research that suggests that tumours exploit the functions of non-cancer cells in their microenvironment to invade and metastasise. “The focus of the project was the gut,” says Trepat. “However, there are many other tissues – lung, breast and skin for example – where our technologies can be applied.”
Turning cells into material building blocks
EpiFold, due for completion in December 2025, will now focus on the most ambitious part of the project – turning cells into building blocks of materials. “We know this will be very hard, but we have already begun to try this,” notes Trepat. “We can create small channels made of cells and are looking at generating cellular pumps.” The attraction of using cells is that they are living. Applications could therefore be made to be self-powering and self-healing, performing functions that would otherwise be hard to engineer from inert material. Potential end uses could be in drug delivery and surgery, where deformable materials would be very useful. “This is high-risk research, and it is still not clear what specific end uses this technology could be for,” adds Trepat. “This work will take time, as we still have so much to learn about the behaviour of these cellular systems.”
Keywords
EpiFold, biohybrid, robotics, epithelial, health, gut, cancer, healthcare
