abstract
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 nextgeneration 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.
keywords
CELLULAR INSULIN-RELEASE; SYNTHETIC BIOLOGY; MULTICELLULAR STRUCTURES; OPTOGENETIC CONTROL; CELLS; ORGANOIDS; SYSTEMS
subject category
Engineering; Materials Science
authors
Gameiro, M; Almeida-Pinto, J; Moura, BS; Mano, JF; Gaspar, VM
our authors
Projects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
acknowledgements
This work was developed within the scope of the project CICECO- Aveiro Institute of Materials, UIDB/50011/2020 (https://doi. org/10.54499/UIDB/50011/2020), UIDP/50011/2020 (https://doi. org/10.54499/UIDP/50011/2020), and LA/P/0006/2020 (https://do i.org/10.54499/LA/P/0006/2020), financed by national funds through the FCT/MEC (PIDDAC). The funding of the European Research Council for the project REBORN (ERC-2019-ADG-883370) is acknowledged. The authors acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through the doctoral grants (Grant No. 2023.04716.BD, J.A.-P. and Grant No. 2021.08331. BD, B.S.M.)

