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Cell-based tissue engineering (TE) has been rapidly evolving to meet the demand of scaffold-free regenerative tissues. Commonly used scaffold-based strategies are often associated with delayed tissue formation, rejection and tissue failure. Scaffold-free TE is a bottom-up methodology that makes use of cell-based soft biomaterials such as cell sheets(CS), spheroids or multishaped microtissues and fiber-shaped multicellular aggregates as building blocks for the construction of functional biomimetic 3D heterogeneous tissues(i.e. consisting of different cell types). Cell-based soft biomaterials are a type of scaffold-free tissues where biomaterials may be used to stimulate and help to orchestrate predetermined functions of natural tissues. The following sections will explore the different cell-based or scaffold-free systems, their advantages, challenges, methods and applications. Major advances in the scaffold-free field resulting from the well-architectured combination of the different methodologies are also reported.

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