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.

中文翻译：

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促进骨组织工程中成骨-血管生成耦合的努力

超过临界尺寸的骨缺损的修复一直是临床实践中的一大挑战。组织工程在有效修复缺损方面表现出巨大的潜力，并且比传统骨移植的副作用更小，其中如何诱导血管化骨形成已被认为是一个关键问题。因此，最近开展了许多研究来尝试促进成骨-血管生成耦合。该综述从支架成分的优化、支架结构的修饰、生物活性物质的负载策略以及合适细胞的使用技巧四个方面对目前改善成骨与血管生成耦合的研究进行了全面的总结和深入的探讨。特别阐述了每种策略的优势和可能的原因以及面临的挑战。此外，在对当前研究的深入分析的基础上，提出了一些有前景的研究方向。本文有望激发新的想法和方法，以更有效地促进新的血管化骨形成。