Abstract

3D Multimodal Bioprinter Capable of Multiscale Deposition to Deal with Tissue Complexity

Fabien Guillemot, CEO, Université Victor Segalen Bordeaux 2

Dealing with tissue complexity and reproducing the functional anisotropy of human tissues remain a puzzling challenge for tissue engineers. Emergence of the biological functions results from dynamic interactions between cells, and with extracellular matrix. Experimental data showing that cell fate (migration, polarization, proliferation…) is triggered by biochemical and/or mechanical cues arising from cell micro-environment suggests that tissue formation obeys to short range orders without reference to a macroscopic or global pattern. In that context, the winning tissue engineering strategy might rely on guiding tissue morphogenesis from the cell to the tissue level.  From a technological point of view, the Laser-Assisted Bioprinting (LAB) technology has emerged as an alternative method to inkjet and bioextrusion methods, thereby overcoming some of their limitations (namely clogging of print heads or capillaries) to pattern living cells and biomaterials with a micron-scale resolution and high cell viability. LAB applications has been limited so far to biofabrication of thin constructs.  In this work, we present an original 3D multimodal and modular bioprinter which combines LAB with microvalve bioprinting. Thanks to this system, cells can be printed at cell resolution using LAB while biomaterials are printed with a coarser resolution (100 µm) using microvalve bioprinting. Interestingly, we show that 1 mm thick 3D constructs can be printed with different biomaterial layer thicknesses (eg made of collagen, agarose) and with multiple cell micropatterns across tissue constructs.  In conclusion, combining technologies featured by different resolution opens new horizons for controlling micro and macro organization of tissue components, and hence for guiding  cellular morphogenesis within thick 3D tissues.