Abstract
Key to most implanted cell free scaffolds for tissue regeneration is the ability to sequester and retain undifferentiated mesenchymal stem cells at the repair site. In this report, syndecan-4, a heparan sulfate containing proteoglycan, was investigated as a unique molecule for use in scaffold functionalization. An electrospun hybrid scaffold comprised of poly (glycerol) sebacate (PGS), silk fibroin and type I collagen (PFC) was used as a model scaffold to develop a procedure and test the hypothesis that functionalization would result in increased scaffold binding of endothelial progenitor cells (EPCs). For these studies both Syndecan-4 and stromal derived factor-1α (SDF-1α) were used in functionalization PFC. Syndecan-4 functionalized PFC bound 4.8 fold more SDF-1α compared to nonfunctionalized PFC. Binding was specific as determined by heparin displacement studies. After culture for 7 days, significantly, more EPCs were detected on PFC scaffolds having both syndecan-4 and SDF-1α compared to scaffolds of PFC with only syndecan-4, or PFC adsorbed with SDF-1α, or PFC alone. Taken together, this study demonstrates that EPCs can be bound to and significantly expanded on PFC material through syndecan-4 mediated growth factor binding. Syndecan-4 with a multiplicity of binding sites has the potential to functionalize and expand stem cells on a variety of scaffold materials for use in tissue regeneration.