Blood and lymphatic vascular network in bone injury repair: from molecular mechanisms to therapeutic strategies.

Although the coupled blood and lymphatic vascular systems are crucial for mammalian homeostasis, they remain understudied in skeletal contexts. The blood vessel system orchestrates oxygen delivery and waste clearance, while the lymphatic network dynamically regulates interstitial fluid balance and immune surveillance. Their embryonic codevelopment allows for synergistic microcirculatory control. Recently, increasing evidence has highlighted the critical role of the blood and lymphatic vascular networks in bone tissue repair. This network effectively promotes and accelerates bone regeneration by spatiotemporally regulating inflammation, bidirectional molecular trafficking, and the secretion of angiocrine/lymphangiocrine factors. Current reviews predominantly address the blood and lymphatic vascular systems in isolation, thereby failing to provide system-level insights into their coordinated regulation during osseous regeneration. This review systematically elaborates on the relationship of the blood and lymphatic vascular systems in bone repair. Furthermore, we describe current tissue engineering studies targeting the blood and lymphatic vascular networks to accelerate bone injury repair and identify critical gaps in this research field. Thus, we aimed to construct a theoretical framework for the coregulation of blood and lymphatic vascular systems in the context of bone injury repair.