3D-printed mesoporous bioactive glass scaffolds for enhancing bone repair via synergetic angiogenesis and osteogenesis

[Display omitted] •Icariin and tetramethylpyrazine integrated scaffolds were constructed with synergetic angiogenesis and osteogenesis.•After implantation, the osteoinductive icariin and angioinductive tetramethylpyrazine were released into the bone defect.•Icariin and tetramethylpyrazine in 3D scaffolds promoted osteogenesis and drove vascularization for bone regeneration. Blood vessels play an important role in bone growth and fracture healing by providing nutrients and oxygen. Although great progress has been made in bone graft materials with good biological and physicochemical properties, vascularization of these materials remains an urgent challenge for bone regeneration. Herein, we report a novel 3D-printed mesoporous bioactive glass (MBG) scaffold (ICA/TMP@MBG) incorporating two unique extracts from Chinese medicine, namely tetramethylpyrazine (TMP) and icariin (ICA), for enhanced vascularization and bone repair. In vitro results showed that ICA/TMP@MBG could significantly upregulate VEGF secretion, thereby facilitating the formation of angiogenesis tubes in human umbilical vein endothelial cells (HUVECs). On the other hand, it can also promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) by stimulating the expression of OPN, ALP, OCN and BMP-2. In addition, in vivo tests further demonstrated that ICA/TMP@MBG could significantly enhance vascularization and accelerate bone healing in a mouse skull defect model. Therefore, the 3D-printed ICA/TMP@MBG has great potential to promote angiogenesis and osteogenesis in bone regeneration.