Synthetic control of implanted engineered liver tissue growth.

Area of Science:

• Biotechnology
• Regenerative Medicine
• Synthetic Biology

Background:

• Scaling engineered tissues to therapeutic sizes is a major hurdle for clinical applications.
• Current methods struggle to produce large-scale organ constructs for transplantation.

Purpose of the Study:

• To develop a novel strategy for generating large-scale engineered organ implants.
• To enable on-demand in vivo expansion of engineered tissues after implantation.

Main Methods:

• Utilized synthetic biology and tissue engineering to create liver tissues capable of in vivo expansion.
• Identified Yes-associated protein (YAP) and growth factor (GF) signaling as key drivers of hepatocyte proliferation.
• Engineered synthetic biology tools to control YAP and GF signaling for controlled tissue growth.

Main Results:

• Demonstrated that YAP and GF signaling are sufficient to drive human hepatocyte proliferation in 3D engineered tissues.
• Successfully induced in vitro and in vivo expansion of engineered liver tissues using synthetic biology triggers.
• Established a proof-of-concept for generating large organ implants through post-implantation outgrowth.

Conclusions:

• The bioengineered on-demand outgrowth via synthetic biology triggering (BOOST) strategy offers a viable solution for scaling engineered tissues.
• This genetic strategy enables the creation of therapeutic-sized organ implants via controlled in situ growth.
• Paves the way for clinical translation of engineered tissues for organ failure treatment.