FGF-1 delivery from multilayer alginate microbeads stimulates a rapid and persistent increase in vascular density

In recent years, great advances have been made in the use of islet transplantation as a treatment for type I diabetes. Indeed, it is possible that stimulation of local neovascularization upon transplantation could improve functional graft outcomes. In the present study, we investigate the use of multilayered alginate microbeads to provide a sustained delivery of FGF-1, and whether this results in increased neovascularization in vivo. Multilayered alginate microbeads, loaded with either 150 ng or 600 ng of FGF-1 in the outer layer, were surgically implanted into rats using an omentum pouch model and compared to empty microbead implants. Rats were sacrificed at 4 days, 1 week, and 6 weeks. Staining for CD31 showed that both conditions of FGF-1 loaded microbeads resulted in a significantly higher vessel density at all time points studied. Moreover, at 6 weeks, alginate microbeads containing 600 ng FGF-1 provided a greater vascular density compared to both the control group and the microbeads loaded with 150 ng FGF-1. Omenta analyzed via staining for smooth muscle alpha actin showed no variation in mural cell density at either 4 days or 1 week. At 6 weeks, however, omenta exposed to microbeads loaded with 600 ng FGF-1 showed an increase in mural cell staining compared to controls. These results suggest that the sustained delivery of FGF-1 from multilayered alginate microbeads results in a rapid and persistent vascular response. An increase in the local blood supply could reduce the number of islets required for transplantation in order to achieve clinical efficacy.