NEW APPROACHES TO TISSUE REGENERATION AND REPAIR

Several Heparin Binding Growth Factors (HBGFs) are thought to play a K ey role in the natural processes of tissue regeneration or repair afte r being released by neighbouring, inflammatory or circulating cells as well as from extracellular matrix associated heparan sulfate proteogl ycosaminoglycans. In order to better understand how the bioavailabilit y of these HBGFs can take part in the regulation of the wound healing processes, we have studied the healing effect of various chemically su bstituted dextrans (CMDBS) selected for their affinity for HBGFs, alon e and in association with HBGFs. The CMDBS was obtained by substitutio n of methylcarboxylic (CM), benzylamide (B) and benzylamine sulfonate (S) groups in proportion of 83%, 23% and 13% respectively for CMDBS K that we have further used (Mauzac et al., 1985 Biomaterials. 6: 61-63) . CMDBS K could 1: potentiate the biological activity of 1 or 2 FGFs, 2: protect 1 and 2 FGFs against thermal or pH inactivation, 3: protect a and b FGFs against proteolytic degradation (Tardieu et al., 1992 J. Cell. Physiol. 150: 194-203). CMDBS K was tested alone in cutaneous a nd bone wound healing models and for its ability to stabilize FGFs. Ra ts were punched and skin regeneration was studied by morphometric and histological analysis. The wounds (6 mm diameter) were filled with col lagen plaster alone or soaked with CMDBS. CMDBS K in collagen plaster was able to induce a remarkable effect both on the kinetics and on the quality of the restored skirt. These results suggest that endogenous growth factors naturally released during the regeneration process coul d be trapped, protected and released by CMDBS. Taking note of the ubiq uitous distribution of FGFs and their ability to stimulate a wide rang e of target cells, we have looked at the effect of CMDBS K in a calvar ian bone defect healing. Adult rats were trephined (3 mm diameter) and healing of their defects were studied after 21 days. Only those treat ed with CMDBS show significant new bone formation and filling of defec ts. In conclusion, biopolymers could be designed to mimic some of the mechanisms regulating the bioavailability of growth factors and hence be used as wound healing agents.