Abstract

4D Bioprinting: Programming Self-Organization to Engineer Biological Tissues

Fabien Guillemot, Chief Executive Officer, Poietis

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 at the cell level.

Bioprinting has been defined as “the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies”. 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.

By harnessing this high cell printing resolution, we observe that tissue self-organization depends on the cell patterns initially printed by LAB, as well as cell types. We introduce from experiments performed in vitro and in vivo the 4D Bioprinting paradigm. This later relies on programming self-organisation, meaning determining appropriate 3D micropatterns (blueprints) of tissue components so that a specific tissue function emerges with time through interaction between components (internal) and interactions with host (external).