CMDBS, FUNCTIONAL ANALOGS OF SULFATE HEPA RANES, USED AS BONE HEALINGAGENTS

Several Heparin-Binding Growth Factors (HBGFs) are known to play an im portant role in bone repair. When osseous tissue is injured, an import ant increase of protease activities and a massive release of HBGFs occ ur. The local increase in HBGFs content at the wounded site, produced by a release of this factors from cells implicated in haemostasis and inflammatory reaction and from extracellular matrix associated heparan sulfate proteoglycans (HSPGs), seems to be a crucial step in bone hea ling. The proteolysis associated with the tissue injury probably limit s the growth factors activies at the wound site. In order to define th e bone healing potential of molecules that would be able to protect HB GFs against proteolytic activation, we studied the effect of derived d extrans, named carboxymethyl-benzylamide-sulfonated dextrans (CMDBS), behaving as heparan like molecules, in 5 mm in diameter skull trepaned defects in young adult rats. In this model CMDBS induced an important bone regeneration in a dose dependent manner while controls were not repaired. In CMDBS treated animals the defects were repaired and conta ined a tissue of normal appearance; in several treated animals the sag ittal suture, initially removed by the trephination, was restored. Thi s remarkable bone healing potential of CMDBS may result from the capac ity to protect the endogenous HBGFs from proteolysis and to modulate t heir biological activities, in a similar manner to that observed for f ibroblast growth factors and HSPGs. CMDBS represent a new form of bone healing agents, which have the advantage of being produced by a contr olled chemical synthesis, and of avoiding the use of exogenous growth factors because of their capacity to enhance the bone healing potentia l of the endogenous growth factors.