TEMPORAL CHANGES DURING BONE REGENERATION IN THE CALVARIUM INDUCED BYOSTEOGENIN

Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of defects treated with either rat insoluble collagenous bone mat rix (ICBM) or partially purified bovine osteogenin, a bone-inductive p rotein, reconstituted with ICBM (OG/ICBM). Repair of all defects was s imilar histologically throughout the first 3 days, characterized by ac ute, then chronic inflammation and granulation tissue formation. In de fects treated with OG/ICBM, cartilage and osteoblasts were present at day 5. By day 9, cartilage and osteoid production were active. New bon e showed hematopoietic tissue by day 11; a complete bone bridge was es tablished by day 21. By day 42, fatty marrow was present. Defects trea ted with ICBM alone showed islands of cartilage and bone embedded in c onnective tissue at day 9, which reached peak maturity by day 14. In t hese and in untreated defects, significant osteoblastic and osteoclast ic activity, located primarily at the margins of the defects, subsided by day 28. Untreated defects gradually filed in with fibrous connecti ve tissue which matured throughout 156 days. Radiopacity, quantified b y computerized image analysis, increased significantly between days 9 and 11 in OG/ICBM-treated defects, and remained greater (P < 0.05) tha n that of the ICBM-treated defects. There was a more gradual increase in radiopacity in ICBM-treated defects. The sequence of morphologic ev ents during calvarial bone regeneration was very similar to that descr ibed previously for heterotopic bone formation induced by demineralize d bone matrix.