The development, maintenance of healthy bone and regeneration of injured tissue in the human body comprise a set of intricate and finely coordinated processes. However, an analysis of current bone regeneration strategies shows that only a small fraction of well-reported bone biology aspects has been used as inspiration and transposed into the development of therapeutic products. Specific topics that include inter-scale bone structural organization, developmental aspects of bone morphogenesis, bone repair mechanisms, role of specific cells and heterotypic cell contact in the bone niche (including vascularization networks and immune system cells), cell-cell direct and soluble-mediated contact, extracellular matrix composition (with particular focus on the non-soluble fraction of proteins), as well as mechanical aspects of native bone will be the main reviewed topics. In this Review we suggest a systematic parallelization of (i) fundamental well-established biology of bone, (ii) updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and (iii) critical discussion of how those individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches. We aim at presenting a perspective on unexplored aspects of bone physiology and how they could be translated into innovative regeneration-driven concepts.

人体健康骨骼的发育、维持和受损组织的再生包括一系列复杂且精细协调的过程。然而，对当前骨再生策略的分析表明，只有一小部分已得到充分报道的骨生物学方面被用作灵感并转化为治疗产品的开发。具体主题包括尺度间骨结构组织、骨形态发生的发育方面、骨修复机制、特定细胞的作用和骨生态位中的异型细胞接触（包括血管化网络和免疫系统细胞）、细胞间直接和可溶性-介导的接触、细胞外基质成分（特别关注蛋白质的不溶性部分）以及天然骨的机械方面将是主要审查主题。在这篇综述中，我们建议系统地并行化（i）基本的、完善的骨生物学，（ii）对天然和受伤组织中发生的生物现象的理解的更新和最新进展，以及（iii）对这些个体如何进行批判性讨论这些方面已转化为使用生物材料和其他组织工程方法的组织再生策略。我们的目标是提出关于骨生理学未探索方面的观点，以及如何将它们转化为创新的再生驱动概念。