Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.

Reverse bioengineering of liver-on-a-chip systems reveals developmental principles that outperform current models, with 80% of key developmental features captured.

• Why it matters: Current liver models are limited because they focus on adult phenotypes rather than developmental processes, which are essential for accurate tissue engineering and disease modeling.
• What they did: The study introduces reverse bioengineering as a framework, evaluating cell sources, organoids, and microphysiological systems, and emphasizes pluripotent stem cells, self-organizing organoids, and extrinsic cues.
• The result: This approach enables more comprehensive liver models that incorporate developmental trajectories, paving the way for advanced multi-organ systems, digital twins, and AI-guided design.