Project Detail |
During embryonic development, organs emerge through highly dynamic processes driven by complex shape-transformations that sculpt their final shape, composition, and function. Despite this, existing approaches to organ bioprinting employ static hydrogels that are not capable of supporting morphogenetic shape changes. Further, we lack an understanding of how key morphogenetic forces such as volumetric tissue growth can be leveraged to re-engineer fundamental tissue shape-morphing behaviours such as bending, buckling, bulging, or twisting. These are major barriers preventing the design of bioprinted tissues that undergo shape-transformations essential for their evolution into a functional final form. Recognising this, the goal of morphoPRINT is to develop a dynamic hydrogel platform that can spatially turn “on” or “off” volumetric growth in bioprinted tissues to direct 4D shape-morphing, and to use this platform to re-engineer morphogenetic shape changes that sculpt the tissue into a more mature form. To realise this goal, we propose ground-breaking technological advances to create hydrogels with independent networks of 1) supramolecular crosslinks that support volumetric growth and 2) photoresponsive covalent crosslinks that can be spatially activated to resist volumetric growth. We will use this platform to explore how spatial patterns of volumetric growth can drive tissue bending, buckling, and bulging, which will lead to a new conceptual understanding of the physical principles that drive tissue shape-morphing. We will then apply these principles towards the design of bioprinted heart tubes that undergo embryonic-like looping into an early 4-chamber structure. morphoPRINT will enable, for the first time, bioprinted organs that undergo programmable shape-morphing. This will set the stage for a new horizon in organ-engineering research focused on recapitulating physical aspects of morphogenesis rather than just the end-stage geometrical structure of the organ. |