Multiscale porous scaffolds constructed of carbonate apatite honeycomb granules for bone regeneration

The use of scaffolds with pores ranging from macroscale to nanoscale (i.e., multiscale pores), is an effective strategy to achieve favorable bone regeneration. Here, we report the fabrication of multiscale porous scaffolds (MPSs) and evaluate the effects of macropores (>100 μm) and micropores (<10 μm) on bone regeneration in the early to medium term. MPSs were constructed from interconnecting carbonate apatite honeycomb granules. The uniaxial macropores penetrating the honeycomb granules linked the gaps among the granules, creating an interconnected macroporous architecture. MPSs with different proportions of macropores and micropores were implanted into rabbit femurs. In an early stage, macropores played a crucial role in promoting new bone formation. In the medium term, micropores, rather than macropores, were the dominant factor affecting the replacement of MPSs with new bone. Notably, micropores of 100 nm to 10 μm primarily promoted MPS resorption by osteoclasts, stimulating secondary osteogenesis. Our findings demonstrated that pore size distribution, rather than porosity, was crucial for osteogenesis in the early-to-medium term. Although conventional scaffold development sacrifices mechanical strength to improve bone formation, our findings indicate that optimizing the pore size distribution is a promising strategy to develop scaffolds that satisfy the requirements of both osteogenesis and mechanical strength.