3D-assembly of interactive microgels to grow in vitro vascularized, structured, and beating human cardiac tissues in high-throughput

Generating 3D in vitro functional tissues and organs in the millimeter scale remains an unmet dream of modern medicine. Irrespective of great efforts in the field of tissue engineering to design injectable/pipettable hydrogels or implantable/non-pipettable scaffolds for 3D cell growth, it is not yet possible to generate functional and personalized tissues with native-like structures and mature blood vessels. The main reason for this limitation is that current materials do not recapitulate the complexity and dynamics of the native cell environment. To create personalized human tissues, patient-derived induced pluripotent stem cells can differentiate in any cell type but controlling stem cell expansion, differentiation, and organization inside the same 3D scaffold is not possible up to now, as it requires biomimetic and interactive materials beyond simple hydrogels. HEARTBEAT will break with traditional ways to make 3D biomaterials by assembling and crosslinking a variety of unique pre-programmed, rod-shaped, and interactive microgels instead of molecular building blocks. The main aim is to achieve macroporous, aligned, actuatable, and on-demand degradable constructs after automatically pipetting/mixing different microgels and cells, which is not possible with conventional hydrogels. A compatible high-throughput system will be used to screen the innumerable combinations of design parameters to systematically study (stem)cell-material and cell-cell interactions to grow complex tissue. In HEARTBEAT, I will focus on using the interactive bottom-up microgel assemblies to generate millimeter-scale vascularized beating heart tissues. The project will elucidate how material properties, architectures, and actuation affect human heart tissue formation and vascularization and how the construct has to adapt to the growing tissue over time to provide the right extracellular environment.