DERIVATIZED DEXTRANS (CMDBS) AS PROMOTERS OF BONE HEALING - FACTORS INFLUENCING THEIR EFFECTIVENESS

Like heparin, carboxymethyl benzylamide sulfonate dextrans (CMDBS) are agents protecting heparin-binding growth factors from heat and proteo lytic denaturation, and enhancing their interactions with their recept ors. In the present study we used in a craniotomy model a series of CM DBS (AM6, AM4, EM5) with different substitution ratios in their chemic al active groups, to test their potential as promoters of bone repair. They were matched against dextran, dextran sulfate and sucrose octasu lfate, another functional heparin analogue. AM6, prepared from a 40 kD dextran and containing a high percentage of sulfonated groups, was th e most effective (p < 0.002 versus controls). Sucrose octasulfate had also osteoconductive properties (p < 0.002 vs controls), but fewer tha n AM6 (p = 0.004). The other agents had no effect on bone repair. We a lso tested the role of the injury during surgery of the mid sagittal s inus, which provides the main cranial blood supply. This prevented bon e formation with AM6 (p < 0.001 vs the corresponding vessel-preserved group). In conclusion, CMDBS effectiveness depends on their molecular weight, the presence of sulfonated groups and a proper vascular enviro nment.