Biomaterial based reconstruction is still the most commonly employed method of small bone defect reconstruction. Bone tissue-engineered techniques are improving, and adjuncts such as vascularization technologies allow re-evaluation of traditional reconstructive methods for healing of critical-sized bone defect. Slow infiltration rate of vasculogenesis after cell-seeded scaffold implantation limits the use of clinically relevant large-sized scaffolds. Hence, in vitro vascularization within the tissue-engineered bone before implantation is required to overcome the serious challenge of low cell survival rate after implantation which affects bone tissue regeneration and osseointegration. Mechanobiological interactions between cells and microvascular mechanics regulate biological processes regarding cell behavior. In addition, load-bearing scaffolds demand mechanical stability properties after vascularization to have adequate strength while implanted. With the advent of bioreactors, vascularization has been greatly improved by biomechanical regulation of stem cell differentiation through fluid-induced shear stress and synergizing osteogenic and angiogenic differentiation in multispecies coculture cells. The benefits of vascularization are clear: avoidance of mass transfer limitation and oxygen deprivation, a significant decrease in cell necrosis, and consequently bone development, regeneration and remodeling. Here, we discuss specific techniques to avoid pitfalls and optimize vascularization results of tissue-engineered bone. Cell source, scaffold modifications and bioreactor design, and technique specifics all play a critical role in this new, and rapidly growing method for bone defect reconstruction. Given the crucial importance of long-term survival of vascular network in physiological function of 3D engineered-bone constructs, greater knowledge of vascularization approaches may lead to the development of new strategies towards stabilization of formed vascular structure.

基于生物材料的重建仍然是小骨缺损重建最常用的方法。骨组织工程技术正在不断发展，诸如血管化技术之类的辅助手段可以重新评估传统的重建方法，以修复临界尺寸的骨缺损。种植细胞的支架植入后，血管生成的缓慢浸润速率限制了临床上相关的大型支架的使用。因此，在体外植入前需要在组织工程化的骨骼内进行血管化，以克服植入后低细胞存活率的严重挑战，这种挑战会影响骨骼组织的再生和骨整合。细胞与微血管力学之间的力学生物学相互作用调节有关细胞行为的生物学过程。另外，承重支架要求在血管化后具有机械稳定性，以在植入时具有足够的强度。随着生物反应器的出现，通过流体诱导的剪切应力对干细胞分化进行生物力学调节，并在多物种共培养细胞中协同促进成骨和血管生成分化，从而大大改善了血管形成。血管化的好处显而易见：避免传质限制和氧气剥夺，细胞坏死的显着减少，因此骨骼发育，再生和重塑。在这里，我们讨论了避免陷井并优化组织工程化骨骼的血管化结果的特定技术。细胞来源，支架修饰和生物反应器设计以及技术细节都在这种新的且快速增长的骨缺损重建方法中发挥着关键作用。鉴于血管网络的长期生存在3D工程骨构造的生理功能中至关重要，因此，对血管化方法的更多了解可能会导致开发新的策略来稳定已形成的血管结构。我们讨论了避免陷阱并优化组织工程化骨的血管化结果的特定技术。细胞来源，支架修饰和生物反应器设计以及技术细节都在这种新的且快速增长的骨缺损重建方法中发挥着关键作用。鉴于血管网络的长期生存在3D工程骨构造的生理功能中至关重要，因此，对血管化方法的更多了解可能会导致开发新的策略来稳定已形成的血管结构。我们讨论了避免陷阱并优化组织工程化骨的血管化结果的特定技术。细胞来源，支架修饰和生物反应器设计以及技术细节都在这种新的且快速增长的骨缺损重建方法中发挥着关键作用。鉴于血管网络的长期生存在3D工程骨构造的生理功能中至关重要，因此，对血管化方法的更多了解可能会导致开发新的策略来稳定已形成的血管结构。