Engineering vascularized tissues using natural and synthetic small molecules.

Vascular growth and remodeling are complex processes that depend on the proper spatial and temporal regulation of many different signaling molecules to form functional vascular networks. The ability to understand and regulate these signals is an important clinical need with the potential to treat a wide variety of disease pathologies. Current approaches have focused largely on the delivery of proteins to promote neovascularization of ischemic tissues, most notably VEGF and FGF. Although great progress has been made in this area, results from clinical trials are disappointing and safer and more effective approaches are required. To this end, biological agents used for therapeutic neovascularization must be explored beyond the current well-investigated classes. This review focuses on potential pathways for novel drug discovery, utilizing small molecule approaches to induce and enhance neovascularization. Specifically, four classes of new and existing molecules are discussed, including transcriptional activators, receptor selective agonists and antagonists, natural product-derived small molecules, and novel synthetic small molecules.