Vascularization Properties Of BFGF Loaded Poly (Aldehyde Guluronate) Hydrogel

The development of a hydrogel able to mimic biochemical aspects of extracellular matrix (ECM) and to induce local angiogenesis by controlled release of angiogenic growth factors (GFs) could be applied in the treatment of several ischemic diseases. In this study, heparin-gelatin conjugate (HGC) was synthesized and incorporated into poly (aldehyde guluronate) (PAG) hydrogels to form synthetic ECM that mimic fundamental functionalities of natural ECM such as protects the heparin-binding growth facto from rapid clearance. To determine optimum conditions for GF delivery, a preliminary in vitro release study of bFGF from PAG hydrogels at various HGC concentrations were carried out. Moreover, the in vivo angiogenic response to bFGF-loaded PAG hydrogels was performed using chick chorioallantoic membrane (CAM) model and rat dorsal air sac model.Polyguluronate (PG) was isolated from sodium alginate by acid hydrolysis, and then PG was oxidized by sodium periodate to PAG. Aminated gelatin was prepared with ethylenediamine in the presence of water-soluble carbodiimide. HGC was synthesized by reductive amination reaction, and then bFGF bound HGC, PAG and aminated gelatin were mixed, which resulted in the formation of covalently crosslinked hydrogel. Compared to oxidized alginate hydrogel, PAG hydrogel degraded more slowly and provided a mechanism for modulating the biological activity of bFGF and controlled release of bFGF.bFGF loaded hydrogel samples were implanted into the chorioallantoic membrane of fertilized chicken eggs and rat dorsal subcutaneous pockets and the resulting neovascularization response measured. The best vascularization was observed in CAM model and rat dorsal air sac model in the presence of 0.5% HGC and 1% HGC, respectively. Significant numbers of neovessels were generated inside hydrogel implants. The ability to stimulate localized microvessel growth at controlled rates for extended times through the release of GFs from covalently linked, heparin-supplemented PAG hydrogels will provide a therapeutic tool for the local treatment of ischemic tissue and wound healing.