Beta-TCP scaffolds with rationally designed macro-micro hierarchical structure improved angio/osteo-genesis capability for bone regeneration.

The design of hierarchical porous structure in scaffolds is crucial for bone defect regenerative repair. However, bioceramic materials present a challenge in precisely constructing designed micropores owing to the limitation of forming process. To investigate micropore shape influences bone regeneration in bioceramic scaffolds with macropores, hierarchical porous scaffolds with interconnective macropores (~400 μm) and two types of micropores (spherical and fibrous) were prepared using a combination of direct ink writing (DIW) and template sacrifice methods. Compared to the scaffold with spherical micropores, the scaffold with highly interconnected fibrous micropores significantly improved cell adhesion and upregulated osteogenic and angiogenetic-related gene expression in mBMSCs and HUVECs, respectively. Furthermore, in vivo implantation experiments showed that hierarchical scaffolds with fibrous micropores accelerated the bone repair process significantly. This result can be attributed to the high interconnectivity of fibrous micropores, which promotes the transportation of nutrients and waste during bone regeneration. Our work demonstrates that hierarchical porous scaffold design, especially one with a fibrous micropore structure, is a promising strategy for improving the bone regeneration performance of bioceramic scaffolds.