Angiogenesis induced by controlled release of neuropeptide substance P.

The in vivo recruitment of circulating host cells to the site to be regenerated is one of the promising strategies for therapeutic angiogenesis. Substance P (SP), a member of neuropeptides, mediates pain perception and regulates wound healing, inflammation, tumor cell proliferation, and angiogenesis. This SP enhanced the migration, adhesion, and angiogenic gene expression of granulocytes in vitro. A biodegradable hydrogel was prepared from an anionic derivative of gelatin to achieve the controlled release of SP in vivo. When the anionic gelatin hydrogels incorporating SP were subcutaneously implanted into the mouse back, significant angiogenesis was induced around the site implanted, in contrast to the injection of SP solution. In vivo accumulation of granulocytes around the implanted sites was observed. It is concluded that the controlled release of SP efficiently induced the recruitment and the subsequent activation of granulocytes, one of the circulating cells with angiogenic activities, from the blood circulation into the site implanted, resulting in enhanced angiogenesis.