Angiogenic and osteogenic effects of flavonoids in bone regeneration

Bone is a highly vascularized tissue that relies on a close spatial and temporal interaction between blood vessels and bone cells. As a result, angiogenesis is critical for bone formation and healing. The vascular system supports bone regeneration by delivering oxygen, nutrients, and growth factors, as well as facilitating efficient cell–cell contact. Most clinical applications of engineered bone grafts are hampered by insufficient vascularization after implantation. Over the last decade, a number of flavonoids have been reported to have osteogenic–angiogenic potential in bone regeneration because of their excellent bioactivity, low cost, availability, and minimal in vivo toxicity. During new bone formation, the osteoinductive nature of certain flavonoids is involved in regulating multiple signaling pathways contributing toward the osteogenic–angiogenic coupling. This review briefly outlines the osteogenic–angiogenic potential of those flavonoids and the mechanisms of their action in promoting bone regeneration. However, further studies are needed to investigate their delivery strategies and establish their clinical efficacy. Flavonoids such as Icariin, Quercetin and few others exhibit angiogenic‐osteogenic coupling. These compounds stimulate the expression of genes regulating osteogenesis and operate as autocrine signals, promoting bone cell repair and survival while simultaneously stimulating angiogenesis in a paracrine manner. The angiogenic‐osteogenic potential of many such flavonoids is yet to be untapped and are scope for future research in the field of bone tissue engineering