The interaction of chitosan with fibroblast growth factor-2 and its protection from inactivation

Application of ultraviolet light (UV) irradiation to a photocrosslinkable chitosan (Az-CH-LA) aqueous solution including fibroblast growth factor-2 (FGF-2) results within 30s in an insoluble, flexible hydrogel. The retained FGF-2 molecules in the chitosan hydrogel remain biologically active, and are released from the chitosan hydrogel upon the in vivo biodegradation of the hydrogel. In view of these findings, we here tested the interaction of chitosan with FGF-2, thereby modifying and stabilizing the FGF-2 activity from inactivations. The photocrosslinkable chitosan hydrogel has a low affinity for FGF-2 (Kd = 6.12 x 10(-7) M). Soluble chitosan (CH-LA; Az-CH-LA without photocrosslinkable azide group) substantially prolonged the biological half-life time of FGF-2. Furthermore, CH-LA could protect the FGF-2 activity from inactivation, such as heat, proteolysis, and acid. The effect of chitosan on the FGF-2 activity is of a protective nature, since it had no effect of modifying the FGF-2 activity directly on growth of human umbilical vein endothelial cells (data not shown). Thus, one of the ways by which the chitosan potentiated the FGF-2 activity could be through protecting it from inactivations by the interaction between FGF-2 and chitosan molecules. (C) 2004 Elsevier Ltd. All rights reserved.