Abstract:  Clues for cell survival emanate from growth factors and ECM proteins. Previous studies suggest that PDGF and fibronectin (FN) are independent survival factors for mesenchymal cells. Here we demonstrate that PDGF bound to FN on a surface is required for mesenchymal cell survival. Radiolabeled PDGF-BB bound intact FN with a KD at 10-8 M. Similar affinities were observed with FNIII1-2 and FNIII12-V15. No binding was observed to FN70, FNIII3-6 or FNIII8-11. Similar data were obtained with plasmon surface resonance regardless of which binding partner served as the ligand. 30 ng/ml PDGF supported FN-null cell survival only in the presence of surface-bound FN or FN growth factor (GF)-binding domains. However, FNGF-binding domains enhanced adult dermal fibroblast migration to PDGF whether the domains where surface-bound or in solution. FNIII8-11 plus FNIII12-V15 tethered to intermolecularly crosslinked hyaluronan plus 15 ng PDGF-BB markedly enhanced porcine cutaneous wound healing at 4 days as judged by re-epithelialization (90%), granulation tissue formation (100%) and angiogenesis (150%) (P<0.01). These data suggest that surface-bound FN-PDGF complexes are required for mesenchymal cell survival. The study has potentially important implications for the delivery of GFs using engineered biomaterials containing FN GF-binding domains for wound healing treatments.

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