Recent advances in cell sheet-based tissue engineering for bone regeneration.

In conventional bone tissue engineering, cells are seeded onto scaffolds to create three-dimensional tis-sues, but the cells on the scaffolds are unable to effectively perform their physiological functions due to their low density and viability. Cell sheet (CS) engineering is expected to be free from this limitation. CS engi-neering uses the principles of self-assembly and self-organization of endothelial and mesenchymal stem cells to prepare CSs as building blocks for engineering bone grafts. This process recapitulates the native tissue de-velopment, thus attracting significant attention in the field of bone regeneration. However, the method is still in the pre-basic experimental stage in bone defect repair. To make the method clinically applicable and valu-able in personalized and precision medicine, current research is focused on the preparation of multi-functionalized building blocks using CS technologies, such as three-dimensional layered CSs containing mi-crovascular structures. Considering the great potential of CS engineering in repairing bone defects, in this review, the types of cell technologies are first outlined. we then summarize the various types of CSs as build-ing blocks for engineering bone grafts. Further, the specific applications of CSs in bone repair are discussed. Finally, we present specific suggestions for accelerating the application of CS engineering in the clinical treatment of bone defects.