title: A Heparin-Mimicking Block Copolymer Both Stabilizes and Increases the Activity of Fibroblast Growth Factor 2 (FGF2).
abstract: 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.
authors: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors: Samantha J
authors: SJ
authors: Paluck
authors: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors: Thi H
authors: TH
authors: Nguyen
authors: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors: Jonghan P
authors: JP
authors: Lee
authors: Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles , 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 United States.
authors: Heather D
authors: HD
authors: Maynard
mesh_terms: D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008689:Methacrylates / Q000737:chemistry* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D008689:Methacrylates; D011092:Polyethylene Glycols; D011108:Polymers; D013451:Sulfonic Acids; C524499:polyethylene glycol methacrylate; C077114:styrenesulfonic acid polymer