Human progenitor cell recruitment via SDF-1α coacervate-laden PGS vascular grafts

Host cell recruitment is crucial for vascular graft remodeling and integration into the native blood vessel; it is especially important for cell-free strategies which rely on host remodeling. Controlled release of growth factors from vascular grafts may enhance host cell recruitment. Stromal cell-derived factor (SDF)-1 alpha has been shown to induce host progenitor cell migration and recruitment; however, its potential in regenerative therapies is often limited due to its short half-life in vivo. This report describes a coacervate drug delivery system for enhancing progenitor cell recruitment into an elastomeric vascular graft by conferring protection of SDF-1 alpha. Heparin and a synthetic polycation are used to form a coacervate, which is incorporated into poly(glycerol sebacate) (PGS) scaffolds. In addition to protecting SDF-1 alpha a, the coacervate facilitates uniform scaffold coating. Coacervate-laden scaffolds have high SDF-1 alpha loading efficiency and provide sustained release under static and physiologically-relevant flow conditions with minimal initial burst release. In vitro assays showed that coacervate-laden scaffolds enhance migration and infiltration of human endothelial and mesenchymal progenitor cells by maintaining a stable SDF-1 alpha gradient. These results suggest that SDF-1 alpha coacervate-laden scaffolds show great promise for in situ vascular regeneration. (C) 2013 Elsevier Ltd. All rights reserved.