Cell sheet engineering

Abstract

Cell sheet engineering enables scaffold-free tissue reconstruction, while preserving native cell–cell junctions and extracellular matrix architecture. However, the clinical translation of this technology has been hindered by high production costs, limited open-source protocols, regulatory challenges and functional limitations, in particular with regards to mechanical stability. In this Review, we first describe how cell sheets are fabricated using stimuli-responsive substrates and examine their applications in cardiac, hepatic, uterine, tendon, ligament and paediatric contexts. We then discuss key mechanical considerations in cell sheet engineering, including strategies to modulate mechanical properties through sheet stacking, anisotropy control through micropatterning, and cyclic mechanical conditioning. By addressing technical innovations and remaining challenges, we provide a framework for expanding the utility of cell sheet engineering to mechanically demanding tissue environments. Cell sheet engineering offers a scaffold-free approach to tissue reconstruction. This Review outlines fabrication methods, key mechanical design strategies and innovations aimed at enabling the use of cell sheets in mechanically demanding tissues.