Tissue Engineering Microtissue: Construction, Optimization, and Application.

Until now, there is no clear definition of microtissue; it usually refers to the microtissue formed by the aggregation of seed cells under the action of cell-cell or cell-extracellular matrix (ECM). Compared with traditional cell monolayer culture, cells are cultivated into a three-dimensional microstructure in a specific way. The microstructure characteristics of microtissue are similar to natural tissues and can promote cell proliferation and differentiation. Therefore, it has a broader range of biomedical applications in tissue engineering. The traditional tissue engineering strategy is to add high-density seed cells and biomolecules on a preformed scaffold to construct a tissue engineering graft. However, due to the destruction of the ECM of the cells cultured in a monolayer during the digestion process with trypsin, the uneven distribution of the cells in the scaffold, and the damage of various adverse factors after the cells are implanted in the scaffold, this strategy is often ineffective, and the subsequent applications still face challenges. This article reviews the latest researches of a new strategy-tissue engineering microtissue strategy; discuss several traditional construction methods, structure, and function optimization; and practical application of microtissue. The review aims to provide a reference for future research on tissue engineering microtissue. Impact statement The traditional tissue engineering strategies have several disadvantages, researchers have conducted extensive research on tissue engineering microtissues in recent years, and they make significant progress. Microtissue is a kind of microtissue with three-dimensional structure, its microstructure is similar to that of natural tissue. In addition, microtissue implantation can protect cells from mechanical interference, inflammation, and other adverse factors. Furthermore, it improves the survival rate of cells and the therapeutic effect of tissue-engineered grafts. However, the practical conditions, advantages, and disadvantages of tissue engineering microtissue have not been fully elucidated. The purpose of this review is to discuss the latest research progress of microtissue and provide a reference for future research.