Formation and maintenance of functional biological architecture relies on the highly complex coordination of forces among cells and their surrounding extracellular matrix. We believe controlled biomanipulation of engineered multicellular biological systems can provide important insight on mesoscale physical principles. In our study, we used microelectromechanical systems technology to form arrays of 3D fibrous microtissues. We then performed robot-assisted microsurgery, such as local incisions and implantation, to study if and how they recover their original form and structure.

The cover image for the September 3 issue of Biophysical Journal is an artistic rendering of the microsurgery platform with arrays of microtissues constrained by microfabricated pillars serving as cantilevers. The cells are embedded inside a collagen matrix. The final form of the tissues is defined by the rules of self-assembly as well as boundary conditions. Fine tweezers, ultrasharp blades, and microscissors are used as end-effectors for a programmable six degrees of freedom microrobot to perform microsurgical operations. As all the parameters are quantified and under our control, we could recapitulate the experimental conditions with our computational modeling framework. Experiments and computer simulations led us to the conclusion that bulk and surface stresses together drive the tissue reconstruction process.

With the cover, we emphasize the unique contribution of dexterous robotic systems to fundamental research in mechanobiology. The tools and techniques are not limited to engineered tissues, but are applicable to any small-scale 3D biological model, including organoids and embryos. We are hoping to extend the capabilities of both the platform and the computational model to better inform decisions in tissue engineering and regenerative medicine.

For more information on our recent work, please visit our website https://www.epfl.ch/labs/microbs/

- Erik Mailand, Bin Li, Jeroen Eyckmans, Nikolaos Bouklas, Mahmut Selman Sakar