Controlling the orientation of a cell-synthesized extracellular matrix by using engineered gelatin-based building blocks

In tissue engineering there is growing interest in fabricating highly engineered platforms designed to instruct cells towards the synthesis of tissues that reproduce their natural counterpart. In this context, a fundamental factor to take into account is the control over the final tissue orientation, especially for what concerns the replication of load-bearing tissues whose functions are strictly related to their microstructural organization. Starting from this point, in this work we have engineered a gelatin-based hydrogel in order to be patterned by 2-photon polymerization (2PP) lithography for the fabrication of instructive free standing building blocks designed to produce anisotropic collagen-based μtissues. Biological results clearly highlighted the strong relationship between μtissue orientation and such topographies, which resulted in a crucial element in the production of highly anisotropic μtissues.