Honeycomb scaffolds capable of ectopic osteogenesis: Histological evaluation of osteoinduction mechanism

Scaffolds capable of inducing ectopic osteogenesis (i.e., osteoinduction) have the potential to treat congenital and massive bone defects. However, the mechanisms underlying osteoinduction remain elusive, largely because of rapid tissue changes occurring early in the process. A model with decelerated osteoinduction is, therefore, needed. Here, we developed carbonate apatite honeycomb scaffolds capable of osteoinduction in rabbit muscle, which inherently exhibits minimal osteoinduction. The key events observed were: (1) fibrin accumulation in scaffolds at week 1; (2) appearance of tartrate‐resistant acid phosphatase (TRAP)‐ and RAM11‐positive cells and formation of collagen fibers and blood vessels between weeks 2 and 3; (3) appearance of osteocalcin‐positive cells and decrease in the number of TRAP‐positive cells between weeks 3 and 4; (4) continuous proliferation of osteocalcin‐positive cells at postoperative week 4 and formation of osteoid and mineralized tissues at weeks 8 and 12, respectively. These findings suggest that the appearance of TRAP‐positive cells that are considered foreign body giant cells is essential for collagen formation, angiogenesis, and osteogenesis. These insights may aid in the development of scaffolds for bone tissue engineering. The key events of osteoinduction observed are: (1) fibrin accumulation in scaffolds; (2) appearance of tartrate‐resistant acid phosphatase (TRAP)‐ and RAM11‐positive cells and formation of collagen fibers and blood vessels; (3) appearance of osteocalcin‐positive cells and decrease in the number of TRAP‐positive cells; (4) continuous proliferation of osteocalcin‐positive cells and formation of osteoid and mineralized tissues.