Polysaccharide electrospun fibers with sulfated poly(fucose) promote endothelial cell migration and VEGF-mediated angiogenesis

Abstract

Vascularization of tissue-engineered constructs is critical for proper cell and graft survival. In order to achieve this, pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), are often incorporated into scaffolds by methods that either involve multiple steps or risk compromising protein bioactivity. In this study, we demonstrate a simple approach to incorporate VEGF into polysaccharide electrospun fibers by taking advantage of the interactions between VEGF and sulfated polysaccharide, fucoidan. Pullulan/dextran (P/D) electrospun fibers (diameter ∼500 nm) incorporating fucoidan were fabricated by a one-step electrospinning process. Thereafter, VEGF was loaded onto the scaffolds. By varying the content of the chemical crosslinker, trisodium trimetaphosphate (STMP), from 10 to 12 and 16 wt% (denoted as STMP10, 12 and 16 respectively), the extent of fucoidan incorporation was significantly enhanced (<2.5 mg g⁻¹ for STMP10 vs. 5 mg g⁻¹ for STMP12 and 16). In addition, increased fucoidan content resulted in prolonged retention of VEGF bioactivity (≥14 days for STMP12 and 16 vs. 3 days for STMP10 and 1 day for VEGF by bolus delivery). Subcutaneous implantation of P/D scaffolds in mice demonstrated enhanced angiogenic response towards fucoidan and VEGF loaded scaffolds at 14 days post-implantation. In addition, P/D constructs supported rapid cellular infiltration and complete biodegradation of the scaffolds was observed at 7 days post-implantation. Taken together, the results demonstrate the potential of P/D electrospun fibers endowed with fucoidan as tunable reservoirs for the effective delivery of VEGF to control vascularization of tissue-engineered constructs.