Cell-based mechanisms and strategies of co-culture system both in vivo and vitro for bone tissue engineering

The lack of a functional vascular supply has been identified as a major challenge limiting the clinical introduction of stem cell-based bone tissue engineering (BTE) for the repair of large-volume bone defects (LVBD). Various approaches have been explored to improve the vascular supply in tissue-engineered constructs, and the development of strategies that could effectively induce the establishment of a functional vascular supply has become a major goal of BTE research. One of the state-of-the-art methods is to incorporate both angiogenic and osteogenic cells in co-culture systems. This review clarifies the key concepts involved, summarises the cell types and models used to date, and systematically evaluates their performance. We also discuss the cell-to-cell communication between these two cell types and the strategies explored in BTE constructs with angiogenic and osteogenic cells to optimise their functions. In addition, we outline unresolved issues and remaining obstacles that need to be overcome for further development in this field and eventual successful repair of LVBD.