Multilineage Constructs for Scaffold‐Based Tissue Engineering: A Review of Tissue‐Specific Challenges

There is a growing interest in the regeneration of tissue in interfacial regions, where biological, physical, and chemical attributes vary across tissue type. The simultaneous use of distinct cell lineages can help in developing in vitro structures, analogous to native composite tissues. This literature review gathers the recent reports that have investigated multiple cell types of various sources and lineages in a coculture system for tissue-engineered constructs. Such studies aim at mimicking the native organization of tissues and their interfaces, and/or to improve the development of complex tissue substitutes. This paper thus distinguishes itself from those focusing on technical aspects of coculturing for a single specific tissue. The first part of this review is dedicated to variables of cocultured tissue engineering such as scaffold, cells, and in vitro culture environment. Next, tissue-specific coculture methods and approaches are covered for the most studied tissues. Finally, cross-analysis is performed to highlight emerging trends in coculture principles and to discuss how tissue-specific challenges can inspire new approaches for regeneration of different interfaces to improve the outcomes of various tissue engineering strategies.