A single low dose of RGTA (R), a new healing agent, hastens wound maturation and enhances bone deposition in rat craniotomy defects

RGTA(R), a new family of dextran-derived healing agents, promotes the repai r of various tissues, including bone. In this study, we examined whether a dose of RGTA lower than in our previous studies could still modify the heal ing pattern in craniotomy defects. In 24 rats, two defects (3 mm diameter) were drilled on either side of the calvaria sagittal suture. The right defe ct was filled with a piece of collagen soaked with RGTA in phosphate-buffer ed saline (PBS; 4 mu g/ml), and the left one with collagen soaked in PBS on ly. After 7, 14 and 21 days, the calvaria were removed and processed for hi stometry. On day 7, in contrast with the control defects, the treated sites were inflammation-free and centripetal bone plates had started to grow. By day 14, the bone filling was significantly enhanced in the treated defects (+290%, p < 0.05), and isolated bone nodules had formed within the fibrous connective tissue (= fibrous hammock) joining the defect edges. The hammoc k had already differentiated by day 7 in all the RGTA-treated defects, and it was significantly thicker on days 14 (+190%, p < 0.05) and 21 (+139%, p < 0.05). The colonization of the hammock by mast cells was increased in the treated sites (+320%, p < 0.05 on day 21). On day 7, most of the bony edge s of the treated defects had been resorbed by osteoclasts, while the proces s only started in the controls. These data indicate that a low dose of RGTA modified the cascade of events occurring at the initial stages of repair, so that the tissular maturation of the treated defects was more rapid. In f act the use of RGTA in the wounds provoked a shift from a fibrous repair as seen in the controls, to a bone reconstruction favoring defect closure.