Controlled angiogenic factor release from alginate gels

Abstract

Therapeutic angiogenesis by localized delivery of angiogenic factors is a promising approach to treat patients with cardiovascular disease and to engineer large tissues. Vascular endothelial growth factor (VEGF) is the most common and biologically active form of the VEGF family, which acts as a mitogen to endothelial cells and is capable of specific binding to heparin. However, when VEGF is administered via bolus injection, it can be widely distributed, and its concentration is likely to be within the effective window for only a short time period due to rapid degradation. Delivery of angiogenic factors, using controlled drug delivery strategies, offers great potential to promote angiogenesis at a specific site while reducing the unwanted side effects that may occur with systemic delivery. We now report on the sustained release of VEGF from alginate gels, modified with a heparin-binding peptide. Briefly, a small peptide with the sequence of G5K(βA)FAKLAARLYRKA, which is known to specifically interact with heparin, was chemically conjugated to alginate, and the peptide-modified alginate formed gels after mixing with heparin and VEGF. The release rate of VEGF from the gels slowed in vitro for over 45 days, compared with release from non-modified alginate gels. This result suggests potential applications of alginate gels in promoting angiogenesis for therapeutic purposes, as well as for tissue engineering.