title: Immobilization of heparan sulfate on electrospun meshes to support embryonic stem cell culture and differentiation.
abstract: As our understanding of what guides the behavior of multi- and pluripotent stem cells deepens, so too does our ability to utilize certain cues to manipulate their behavior and maximize their therapeutic potential. Engineered, biologically functionalized materials have the capacity to influence stem cell behavior through a powerful combination of biological, mechanical, and topographical cues. Here, we present the development of a novel electrospun scaffold, functionalized with glycosaminoglycans (GAGs) ionically immobilized onto the fiber surface. Bound GAGs retained the ability to interact with GAG-binding molecules and, crucially, presented GAG sulfation motifs fundamental to mediating stem cell behavior. Bound GAG proved to be biologically active, rescuing the neural differentiation capacity of heparan sulfate-deficient mouse embryonic stem cells and functioning in concert with FGF4 to facilitate the formation of extensive neural processes across the scaffold surface. The combination of GAGs with electrospun scaffolds creates a biomaterial with potent applicability for the propagation and effective differentiation of pluripotent stem cells.
authors.affiliation: Stem Cell Glycobiology Group, School of Materials, University of Manchester, Grosvenor Street, Manchester M1 7HS, United Kingdom.
authors.forename: Kate A
authors.initials: KA
authors.lastname: Meade
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: White
authors.forename: Claire E
authors.initials: CE
authors.lastname: Pickford
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Holley
authors.forename: Andrew
authors.initials: A
authors.lastname: Marson
authors.forename: Donna
authors.initials: D
authors.lastname: Tillotson
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Jason D
authors.initials: JD
authors.lastname: Whittle
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Day
authors.forename: Catherine L R
authors.initials: CL
authors.lastname: Merry
mesh_terms: D000499:Allylamine / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004187:Disaccharides / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology*; D000939:Epitopes / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009844:Oligosaccharides / Q000737:chemistry; D019151:Peptide Library; D011108:Polymers / Q000737:chemistry; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods
chemical_list: D000499:Allylamine; D001672:Biocompatible Materials; D004187:Disaccharides; D000939:Epitopes; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D036341:Intercellular Signaling Peptides and Proteins; D009844:Oligosaccharides; D019151:Peptide Library; D011108:Polymers