RGTA11, A NEW HEATING AGENT, TRIGGERS DEVELOPMENTAL EVENTS DURING HEALING OF CRANIOTOMY DEFECTS IN ADULT RATS

RGTA are chemically defined compounds which pra, ed to be very potent healing agents in various tissue repair models including skin, muscle and nerve. These chemicals are belie, ed to protect endogenously relea sed heparin-binding growth factors and enhance their bioavailability d uring healing, In craniotomy defects that do not heal spontaneously in adults, RGTA promoted dose-dependent skull closure. The aim of this w ork was to characterize, in the same model, the events associated with wound closure by studying the expression of the osteoblastic phenotyp e and the distribution of some matrix proteins during RGTA11-induced b one healing. Craniotomy defects in rats mere implanted with collagen p lasters soaked in a solution of RGTA11 (1.5 mu g per piece). The skull s were removed 30 days after wounding, a stage of almost complete bone filling in treated samples. Bone formed only at the edges of the defe ct in controls, while it formed also at the center in the form of nodu les in the treated samples. RGTA11 modified the amount and distributio n of the tissues including bone in the sounds. In some RGTA11-treated samples, skull closure by bone occurred and the median suture was rest ored. In the treated defects, all;aline phosphatase-positive (osteopro genitor) tells mere far more numerous and were distributed differently . Type I and III collagen and fibronectin deposition was markedly enha nced in the bone compartment of the wounds. Secretory osteoblasts rele ased type III collagen. Osteocalcin expression was enhanced by RGTA11. RGTA11 thus modified the healing pattern by increasing both the cellu larity and the synthesis of a bone-competent extracellular matrix, the reby restoring the original anatomy of the skull, Flat bone regenerati on can be triggered in adults through developmental events (i.e. nodul e formation, secretion of type III collagen by osteoblasts, suture res toration...) that are no longer operative in the wounds of mature indi viduals.