NEW CONCEPTS IN TISSUE-REPAIR - SKIN AS AN EXAMPLE

Several heparin-binding growth factors (HBGFs) are thought to play a k ey role in natural processes of tissue regeneration or repair after re lease from inflammatory or circulating cells acid extracellular matrix -associated heparan sulfate proteoglycosaminoglycans. To clarify how t he bioavailability of these HBGFs can help regulate wound-healing proc esses, we studied the healing effect of various chemically substituted dextrans (RGTA) selected for their affinity for HBGFs. One member of the RGTA family, RGTA11, obtained by substitution of carboxymethyl(CM) , benzylamide (B) and benzylamide sulfonate (S) groups in a proportion of 110 % (CM), 2.6 % (B) and 36.5 % (S) respectively was used in thes e studies. RGTA11 may potentiate the biological activity of fibroblast growth factors 1 and 2 and protect them against heat or pH inactivati on and proteolytic degradation. RGTAI1 was tested in a rat punch-biops y skin-healing model for its ability to enhance wound repair. Wounds w ere filled with collagen plaster alone or soaked with RGTA, and skin r egeneration was studied by histological analysis. In collagen piaster, RGTA11 affected both the kinetics and quality of restored skin. It se ems likely that endogenous growth factors naturally released during th e regeneration process are trapped and protected against natural prote ases, thereby preserving their ability to stimulate tissue repair. Sin ce most known growth factors have a nearly ubiquitous distribution and bind to heparin, our hypothesis was verified by studying the ability of RGTA to induce repair in damaged tissue. We demonstrated that RGTA could stimulate wound repair in various models, including hone, muscle , nerve, cornea and colonic anastomosis. The data presented here conce rn wound-healing in a deep skin model and suggest that heparan-like bi opolymers constitute a new family of tissue-repair agents with a wide variety of potential uses. The efficiency of this approach in cases in which impaired healing is associated with a pathology, as in diabetes , remains to be determined.