THE RELATIONSHIP BETWEEN PDGF-BB, HEPARAN SUGARS AND SKIN WOUND HEALING

Abstract

Platelet-derived growth factor-BB (PDGF-BB) is critical for skin wound healing and has demonstrated clinical effectiveness when topically applied at supra-physiological concentrations to diabetic ulcers. Here we describe an HS fraction, HS6, isolated from a porcine HS mixture by an affinity chromatographic process that used the basic retention domain of PDGF-BB as the ligand. The purified HS6 was enriched for tri- and di-sulfated disaccharides, and demonstrated affinity for other wound healing growth factors besides PDGF-BB, particularly FGF2 and VEGF165. A surface plasmon resonance competition assay using a heparin-coated chip confirmed that HS6 had enhanced affinity for PDGF-BB. HS6 was able to stabilize and enhance the activity of sub-optimal doses of PDGF-BB on human dermal fibroblasts as demonstrated by prolonged PDGFRβ signaling, enhanced proliferation and migration. These results suggest that HS6 can be further developed as a novel wound healing therapy that is able to enhance the activity of endogenously produced PDGF-BB.