HEPARAN-LIKE MOLECULES INDUCE THE REPAIR OF SKULL DEFECTS

Heparin-binding growth factors (HBGFs) are known to stimulate bone rep air when applied to bone lesions, Nevertheless, successful treatments are obtained with high protein doses since HBGFs are rapidly degraded in situ by multiple proteolytic activities associated with the inflamm atory period of tissue healing, Like heparin or heparan sulfates, hepa ran-like molecules, named carboxymethyl-benzylamide-sulfonated dextran s (CMDBS), are known to potentiate fibroblast growth factor activities by stabilizing them against pH, thermal or proteolytic denaturations, and by enhancing their binding with cell surface receptors. We have p ostulated that CMDBS stimulate in vivo bone healing by interacting wit h endogenous HBGFs, spontaneously released in the wounded site, The ef fect of CMDBS on bone repair was studied in a skull defect model in ra ts by computer-assisted radio-morphometry and histomorphometry, Single application of CMDBS in a collagen vehicle to skull defects induced a dose-dependent increase in bone defect closure and new bone formation after 35 days, Complete bony bridging occurred in defects treated wit h 3 mu g CMDBS, whereas bone formation was not observed in vehicle-tre ated defects which contained only dense fibrous connective tissue betw een the defect margins, These results indicate that heparan-like molec ules, such as CMDBS, are able to induce bone regeneration of skull def ects, This action is possibly mediated by potentiation of endogenous g rowth factor activities and/or by neutralization of proteolytic activi ties.