Synthetic vascularization and regeneration in engineered tissues

Project Description
The goal of this NEW PROJECT is to engineer liver tissue grafts in which the timing and extent
of graft vascularization and expansion in a living host is directly manipulable. In vivo, cell-to-cell
communication mediated through paracrine signals is a hallmark of multicellular life, and in the
liver is thought to play a critical role in driving tissue vascularization and growth. In collaborative
studies, the investigators have recently established experimental models of liver tissue that
incorporate hepatocytes, endothelial cells, and stromal cells spatially patterned to bolster these
cell-cell interactions. These interactions enable vascularization regenerative expansion of
engineered human liver tissue both in vitro, in a microfluidic human liver model, and in vivo, in
an ectopically implanted human liver graft. In this proposal, the investigators will build upon
these model systems by leveraging synthetic transcription factors to take control over the
dynamics of paracrine signaling within the engineered livers to enable controlled, on-demand
tissue vascularization and expansion. The specific aims of this new proposal are: (1) To build
functional vasculature in engineered tissue through synthetic vascularization, (2) To establish
on-demand expansion of engineered functional liver tissue through synthetic regeneration, and
(3) To develop approaches for system integration and robustness in suboptimal host
environments. Together, leveraging both in vitro and in vivo models, these efforts will endow
precise control of function, expansion, and engraftment of engineered vasculature and hepatic
parenchyma and will more generally establish a new approach for synthetic control of
engineered tissues that will advance engineered organ grafts closer towards clinical utility.

Grant Number: 5R01EB033821-03
NIH Institute/Center: NIH
Principal Investigator: CHRISTOPHER CHEN