Large-scale perfused tissues via synthetic 3D soft microfluidics

Vascularization of engineered tissues and organoids is a major challenge in regenerative medicine. This study achieves perfusion of multi-mm³ tissue constructs by generating networks of synthetic capillary-scale 3D vessels using a 3D-printable, two-photon-polymerizable hydrogel. Large-scale engineered tissues are shown to be viable, proliferative, and exhibit complex morphogenesis. Single-cell RNA sequencing (scRNAseq) and immunohistochemistry reveal that neural differentiation is significantly accelerated in perfused neural constructs. The platform's versatility is demonstrated through long-term perfusion of neural and liver tissues, opening possibilities for generating human tissue models at unprecedented scale and complexity.

Sergei Grebenyuk, Abdel Rahman Abdel Fattah, Manoj Kumar, Burak Toprakhisar, Gregorius Rustandi, Anja Vananroye, Idris Salmon, Catherine Verfaillie, Mark Grillo, Adrian Ranga