Local and Sustained Vascular Endothelial Growth Factor Delivery for Angiogenesis Using an Injectable System

We hypothesize that a microsphere/hydrogel combination system could be useful for the local and sustained delivery of recombinant human vascular endothelial growth factor (rhVEGF) to enhance angiogenesis in vivo. Poly(d,l-lactide-co-glycolide) (PLGA) microspheres containing rhVEGF were loaded into alginate gels by ionic cross-linking. The rhVEGF release from the system was monitored and bioactivity was tested in vitro. The combination system was subcutaneously injected into mice using a syringe, and new blood vessel formation was evaluated. Sustained rhVEGF release from the combination system was observed for 3 weeks, and the released rhVEGF remained bioactive. Endothelial cell proliferation was significantly enhanced when cells were cultured with the rhVEGF-releasing combination system in vitro. When the combination system was implanted, the granulation tissue layer was thicker with more newly formed blood vessels than that with a single dose VEGF injection. The rhVEGF release was controlled by varying relative portions of microspheres and hydrogels in combination delivery systems, which efficiently promoted new blood vessel formation in vivo. This combination system could be a promising delivery vehicle for therapeutic angiogenesis.