Temporal changes during bone regeneration in the calvarium induced by osteogenin

Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of defects treated with either rat insoluble collagenous bone matrix (ICBM) or partially purified bovine osteogenin, a bone-inductive protein, reconstituted with ICBM (OG/ICBM). Repair of all defects was similar histologically throughout the first 3 days, characterized by acute, then chronic inflammation and granulation tissue formation. In defects treated with OG/ICBM, cartilage and osteoblasts were present at day 5. By day 9, cartilage and osteoid production were active. New bone showed hematopoietic tissue by day 11; a complete bone bridge was established by day 21. By day 42, fatty marrow was present. Defects treated with ICBM alone showed islands of cartilage and bone embedded in connective tissue at day 9, which reached peak maturity by day 14. In these and in untreated defects, significant osteoblastic and osteoclastic activity, located primarily at the margins of the defects, subsided by day 28. Untreated defects gradually filed in with fibrous connective tissue which matured throughout 156 days. Radiopacity, quantified by computerized image analysis, increased significantly between days 9 and 11 in OG/ICBM-treated defects, and remained greater (P < 0.05) than that of the ICBM-treated defects. There was a more gradual increase in radiopacity in ICBM-treated defects. The sequence of morphologic events during calvarial bone regeneration was very similar to that described previously for heterotopic bone formation induced by demineralized bone matrix.