Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair

In the field of bone defect repair, 3D printed scaffolds have the characteristics of personalized customization and accurate internal structure. However, how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after transplantation. Herein, inspired by the unique biological structure of "lotus seedpod", hydrogel microspheres encapsulating deferoxamine (DFO) liposomes were prepared through microfluidic technology as "lotus seeds", and skillfully combined with a three-dimensional (3D) printed bioceramic scaffold with biomimetic "lotus" biological structure which can internally grow blood vessels. In this composite scaffold system, DFO was effectively released by 36% in the first 6 h, which was conducive to promote the growth of blood vessels inside the scaffold quickly. In the following 7 days, the release rate of DFO reached 69%, which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells (BMSCs). It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells (HUVECs) to form the vascular morphology within 6 h in vitro. In vivo, the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α, CD31, OPN, and OCN in the rat femoral defect model, significantly cutting down the time of bone repair. To sum up, this "lotus seedpod" inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future.