Quantitative assessment of cranial defect healing and correlation with theexpression of TGF-beta

Circular parietal defects from 3 to 12 mm in diameter were made in 45 6-mon th old skeletally mature guinea pigs, and animals were sacrificed after sur vival periods of 3 days to 12 weeks. The original defect was harvested in c ontinuity with a rim of surrounding bone and the adjacent dura and pericran ium. After 12 weeks, all 3 and 5 mm defects were completely covered by a br idge of bone, while residual defects were noted within the 8 and 12 mm woun ds. Percentage of new bone formation was significantly higher within 3 mm d efects, than in all larger defects at each time interval from 1 week on (P < .05), reaching a mean of 93% in 3 mm defects and remaining below a mean o f 31% in the remaining defect sizes. Immunolocalization demonstrated an ost eogenic front in which the osteoblasts stained strongly for all isoforms of TGF-beta, with the intensity decreasing after the majority of the defects had reossified; this front was located at the advancing bone edge of the de fect as well as the endocranial side adjacent to the dura. in conclusion, i soforms of TGF-beta are upregulated during a limited "window" of time corre sponding to the period of calvarial reossification, and are localized to os teoblasts within an osteogenic front at the periphery and. Rural surfaces o f the defects.