3D-printed hydroxyapatite (HA) scaffolds combined with exos from BMSCs cultured in 3D HA scaffolds to repair bone defects

The method of 3D printing biotechnology for tissue engineering is widely used in repairing and reconstructing bone defects, which remains a great challenge due to the lack of angiogenesis. Exosomes (exos) derived from bone marrow mesenchymal stem cells (BMSCs) have great potential to promote angiogenesis, especially under hypoxic conditions. This study aimed to explore the effects of 3D hydroxyapatite (HA) scaffolds, which were loaded with exos from BMSCs cultured in 3D HA scaffolds under hypoxic conditions (3D/H-exos), on the repair and reconstruction of bone defects. The exos were extracted from BMSCs cultured in 3D HA scaffolds under hypoxic or normoxic conditions and were taken up by human umbilical vein endothelial cells (HUVECs). The obtained results showed that (3D/H-exos) enhanced proliferation, migration and tube formation in HUVECs via the PTEN/AKT pathway. Moreover, 3D HA scaffolds loaded with 3D/H-exos clearly promoted angiogenesis and osteogenesis in a calvarial defect rat model. This study suggests that 3D HA scaffolds combined with 3D/H-exos are a promising approach to enhance bone repair and regeneration.