title: Vascular smooth muscle cell optimization of vasculogenesis within naturally derived, biodegradable, hybrid hydrogel scaffolds.
abstract: BACKGROUND
  As vascularization represents the rate-limiting step in permanent incorporation of hydrogel-based tissue-regeneration templates, the authors sought to identify the material chemistry that would optimize endothelial cell adhesion and invasion into custom hydrogel constructs. The authors further investigated induction of endothelial tubule formation by growth factor supplementation and paracrine stimulation.
  
  
  METHODS
  Hydrogel scaffolds consisting of combinations of alginate, collagen type I, and chitosan were seeded with human umbilical vein endothelial cells and maintained under standard conditions for 14 days. Cell density and invasion were then evaluated. Tubule formation was evaluated following basic fibroblast growth factor addition or co-culture with human aortic smooth muscle cells.
  
  
  RESULTS
  Human umbilical vein endothelial cells demonstrated greatest cell-surface density and invasion volumes with alginate and collagen (10:1 weight/weight) scaffolds (p < 0.05). Supplementation with basic fibroblast growth factor increased surface density but neither invasion nor tubule formation. A significant increase in tubule content/organization was observed with increasing human aortic smooth muscle cell-to-human umbilical vein endothelial cell ratio co-culture.
  
  
  CONCLUSIONS
  Alginate and collagen 10:1 scaffolds allow for maximal cellularization compared with other combinations studied. Growth factor supplementation did not affect human umbilical vein endothelial cell invasion or morphology. Paracrine signaling by means of co-culture with human umbilical vein endothelial cells stimulated endothelial tubule formation and vascular protonetwork organization. These findings serve to guide future endeavors toward fabrication of prevascularized tissue constructs.
authors.affiliation: New York, N.Y. From the Laboratory of Bioregenerative Medicine and Surgery, Division of Plastic Surgery, Weill Cornell Medical College.
authors.forename: Alyssa Reiffel
authors.initials: AR
authors.lastname: Golas
authors.forename: Justin L
authors.initials: JL
authors.lastname: Perez
authors.forename: Natalia
authors.initials: N
authors.lastname: Fullerton
authors.forename: Nikola
authors.initials: N
authors.lastname: Lekic
authors.forename: Rachel Campbell
authors.initials: RC
authors.lastname: Hooper
authors.forename: Jason A
authors.initials: JA
authors.lastname: Spector
mesh_terms: D000464:Alginates / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D048271:Chitosan / Q000494:pharmacology; D018920:Coculture Techniques; D024042:Collagen Type I / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000494:pharmacology; D008558:Melphalan / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D018919:Neovascularization, Physiologic; D009842:Oligopeptides / Q000494:pharmacology; D019899:Paracrine Communication / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D024042:Collagen Type I; D007074:Immunoglobulin G; D009842:Oligopeptides; C051713:antineoplastic agent K 18; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047981:arginyl-glycyl-aspartic acid; D048271:Chitosan; D008558:Melphalan