Designer mammalian living materials through genetic engineering

Emerging genome editing and synthetic biology toolboxes can accurately program mammalian cells behavior from the inside-out. Such engineered living units can be perceived as key building blocks for bioengineering mammalian cell-dense materials, with promising features to be used as living therapeutics for tissue engineering or disease modeling applications. Aiming to reach full control over the code that governs cell behavior, inside-out engineering approaches have potential to fully unlock user-defined living materials encoded with tailored cellular functionalities and spatial arrangements. Dwelling on this, herein, we discuss the most recent advances and opportunities unlocked by genetic engineering strategies, and on their use for the assembly of next-generation cell-rich or cell-based materials, with an unprecedent control over cellular arrangements and customizable therapeutic capabilities. We envision that the continuous synergy between inside-out and outside-in cell engineering approaches will potentiate the future development of increasingly sophisticated cell assemblies that may operate with augmented biofunctionalities. • Mammalian cell units can be genetically engineered with programmable instructions. • Efforts have been made to merge synthetic biology, materials, and tissue engineering. • Cell-dense assemblies can possess intricate architectures and enhanced functionality. • Genetically designed materials may unlock promising biomedical applications.