Self-assembling tissue modules

摘要

The invention relates to a new approach to constructing cellular aggregates in vitro and their use in methods for producing 3D-tissue constructs in a modular way.;In particular, the invention is directed to a method for in vitro producing a tissue construct comprising:
a) combining living cells to form supracellular aggregates using spatial confinement;b) combining two or more of the supracellular aggregates in a mold or on a biomaterial;c) applying conditions that induce self-assembly within the combined supracellular aggregates to obtain the tissue construct; andd) applying conditions that induce tissue morphogenesis in the tissue construct.

主权项

1. A method for in vitro producing a tissue construct which substantially retains its shape after release from a well, the method comprising:
a) combining living cells to form supracellular aggregates using spatial confinement by condensation of said cells in microwells having an enveloping diameter in the range of 50 μm to 500 μm into supracellular aggregates; b) combining two or more of the supracellular aggregates in a mold or biomaterial comprising a well having a geometric shape and having enveloping diameter of at least 100 μm; c) applying conditions that induce self-assembly within the combined supracellular aggregates to obtain the tissue construct; d) applying conditions that induce tissue morphogenesis in the tissue construct; and e) releasing the tissue construct from the well, wherein the condensation of step a) allows the tissue construct to maintain at least 90% of its non-spherical shape for 150 hours has after said release of the tissue construct from the well having a geometric shape as compared to the shape of the construct while still within the well having geometric shape.