title: Photopatterning of vascular endothelial growth factor within collagen-glycosaminoglycan scaffolds can induce a spatially confined response in human umbilical vein endothelial cells.
abstract: Biomolecular signals within the native extracellular matrix are complex, with bioactive factors found in both soluble and sequestered states. In the design of biomaterials for tissue engineering applications it is increasingly clear that new approaches are required to locally tailor the biomolecular environment surrounding cells within the matrix. One area of particular focus is strategies to improve the speed or quality of vascular ingrowth and remodeling. While the addition of soluble vascular endothelial growth factor (VEGF) has been shown to improve vascular response, strategies to immobilize such signals within a biomaterial offer the opportunity to optimize efficiency and to explore spatially defined patterning of such signals. Here we describe the use of benzophenone (BP) photolithography to decorate three-dimensional collagen-glycosaminoglycan (CG) scaffolds with VEGF in a spatially defined manner. In this effort we demonstrate functional patterning of a known agonist of vascular remodeling and directly observe phenotypic effects induced by this immobilized cue. VEGF was successfully patterned in both stripes and square motifs across the scaffold with high specificity (on:off pattern signal). The depth of patterning was determined to extend up to 500 μm into the scaffold microstructure. Notably, photopatterned VEGF retained native functionality as it was shown to induce morphological changes in human umbilical vein cells indicative of early vasculogenesis. Immobilized VEGF led to greater cell infiltration into the scaffold and the formation of immature vascular network structures. Ultimately, these results suggest that BP-mediated photolithography is a facile method to spatially control the presentation of instructive biological cues to cells within CG scaffolds.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Aurora T
authors.initials: AT
authors.lastname: Alsop
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Jacquelyn C
authors.initials: JC
authors.lastname: Pence
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Weisgerber
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Brendan A C
authors.initials: BAC
authors.lastname: Harley
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: baileyrc@illinois.edu.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001577:Benzophenones / Q000737:chemistry; D003094:Collagen / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D010641:Phenotype; D012754:Sharks; D054457:Tissue Scaffolds / Q000737:chemistry*; D014466:Ultraviolet Rays; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D001577:Benzophenones; D006025:Glycosaminoglycans; D055767:Immobilized Proteins; D042461:Vascular Endothelial Growth Factor A; C047723:benzophenone; D003094:Collagen
keywords: Collagen; Photolithography; Scaffold; VEGF; Vascularization