Efforts to promote osteogenesis-angiogenesis coupling for bone tissue engineering.

Repair of bone defects exceeding a critical size has been always a big challenge in clinical practice. Tissue engineering has exhibited great potential to effectively repair the defects with less adverse effect than traditional bone grafts, during which how to induce vascularized bone formation has been recognized as a critical issue. Therefore, recently many studies have been launched to attempt to promote osteogenesis-angiogenesis coupling. This review summarized comprehensively and explored in depth current efforts to ameliorate the coupling of osteogenesis and angiogenesis from four aspects, namely the optimization of scaffold components, modification of scaffold structures, loading strategies for bioactive substances, and employment tricks for appropriate cells. Especially, the advantages and the possible reasons for every strategy, as well as the challenges, were elaborated. Furthermore, some promising research directions were proposed based on an in-depth analysis of the current research. This paper will hopefully spark new ideas and approaches for more efficiently boosting new vascularized bone formations.