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)-1α 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-1α. 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-1α, the coacervate facilitates uniform scaffold coating. Coacervate-laden scaffolds have high SDF-1α 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-1α gradient. These results suggest that SDF-1α coacervate-laden scaffolds show great promise for in situ vascular regeneration.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Kee-Won
KW
Lee
Noah R
NR
Johnson
Jin
J
Gao
Yadong
Y
Wang
D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D003651:Decanoates / Q000737:chemistry; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry
D054377:Chemokine CXCL12; D003651:Decanoates; D011108:Polymers; C469892:poly(glycerol-sebacate); D005990:Glycerol
Coacervate; Human progenitor cells; Poly(glycerol sebacate); Polycation; Stromal cell-derived factor (SDF)-1α; Tissue engineering