Sustained delivery of vascular endothelial growth factor with alginate beads

Therapeutic angiogenesis is the growth of blood vessels from a pre-existing vasculature for clinical applications such as treating myocardial and limb ischemia. Vascular endothelial growth factor (VEGF) is a potent signal transduction molecule that acts specifically on vascular endothelial cells. Encapsulation of VEGF in a polymer matrix not only protects protein against enzymatic degradation in the body, but also allows proteins to be released at a controllable rate into a localized area. In this study, VEGF was encapsulated in calcium alginate beads by the extrusion/external gelation method, and was subsequently released in PBS and in serum media. The objective was to optimize VEGF encapsulation yield and obtain VEGF release at a constant rate from alginate matrices in vitro. The incorporation of low concentrations of VEGF and NaCl can increase encapsulation yield to 97%. The rate of VEGF release from alginate beads was higher in serum than in PBS, which was due to the capacity of the serum in reducing the electrostatic interaction between alginate and VEGF. The presence of CaCl2 in the release supernatant can shield the alginate interaction with VEGF, and a constant release rate of 6 ng/ml/day may be sustained for 14 days. These results suggest that the alginate-VEGF delivery system may be useful in the development of vascular tissue engineering and wound healing applications. (C) 2004 Elsevier B.V. All rights reserved.