Effects of nanopores on the mechanical strength, osteoclastogenesis, and osteogenesis in honeycomb scaffolds

The scaffold chemical composition and pore architecture are critical for successful bone regeneration. Although the effects of chemical composition, micron-scale pores, and macropores (≥100 μm) are known, those of nanometer-scale pores (nanopores) are unknown. Here, honeycomb scaffolds (HCSs) composed of carbonate apatite and bone mineral, were fabricated with three distinct nanopore volumes, while other parameters were comparable between HCSs. Their compressive strengths and nanopore volumes linearly correlated. The HCSs were implanted into critical-sized bone defects (CSDs) in the rabbit femur distal epiphyses. The nanopore volume affected both osteoclastogenesis and osteogenesis. HCSs with nanopore volumes of ≥0.15 cm3 g-1 promoted osteoclastogenesis, contributing to bone maturation and bone formation within 4 weeks. However, HCSs with nanopore volumes of 0.07 cm3 g-1 promoted significantly less bone maturation and neoformation. Nevertheless, HCSs with nanopore volumes of ≥0.18 cm3 g-1 did not undergo continuous bone regeneration throughout the 12 week period due to excessive osteoclastogenesis, which favored HCS resorption over bone neoformation. When the nanopore volume was 0.15 cm3 g-1, osteoclastogenesis and osteogenesis progressed harmonically, resulting in HCS replacement with new bone. Our results demonstrate that the nanopore volume is critical for controlling osteoclastogenesis and osteogenesis. These insights may help establish a coherent strategy for developing scaffolds for different applications.