Fibroblast growth factor 2 (FGF2)
is a protein involved in cellular
functions in applications such as wound healing and tissue regeneration.
Stabilization of this protein is important for its use as a therapeutic
since the native protein is unstable during storage and delivery.
Additionally, the ability to increase the activity of FGF2 is important
for its application, particularly in chronic wound healing and the
treatment of various ischemic conditions. Here we report a heparin
mimicking block copolymer, poly(styrenesulfonate-co-poly(ethylene glycol) methyl ether methacrylate)-b-vinyl sulfonate) (p(SS-co-PEGMA)-b-VS, that contains a segment that enhances the stability of FGF2
and one that binds to the FGF2 receptor. The FGF2 conjugate retained
activity after exposure to refrigeration (4 °C) and room temperature
(23 °C) for 7 days, while unmodified FGF2 was inactive after
these standard storage conditions. A cell study performed with a cell
line lacking native heparan sulfate proteoglycans indicated that the
conjugated block copolymer facilitated binding of FGF2 to its receptor
similar to the addition of heparin to FGF2. A receptor-based enzyme-linked
immunosorbant assay (ELISA) confirmed the results. The conjugate also
increased the migration of endothelial cells by 80% compared to FGF2
alone. Additionally, the FGF2-p(SS-co-PEGMA)-b-VS stimulated endothelial cell sprouting 250% better than
FGF2 at low concentration. These data verify that this rationally
designed protein-block copolymer conjugate enhances receptor binding,
cellular processes such as migration and tube-like formation, and
stability, and suggest that it may be useful for applications in biomaterials,
tissue regeneration, and wound healing.