title: Alginate-Chitosan Hydrogels Provide a Sustained Gradient of Sphingosine-1-Phosphate for Therapeutic Angiogenesis.
abstract: Sphingosine-1-phosphate (S1P), a bioactive lipid, is a potent candidate for treatment of ischemic vascular disease. However, designing biomaterial systems for the controlled release of S1P to achieve therapeutic angiogenesis presents both biological and engineering challenges. Thus, the objective of this study was to design a hydrogel system that provides controlled and sustained release of S1P to establish local concentration gradients that promote neovascularization. Alginate hydrogels have been extensively studied and characterized for delivery of proangiogenic factors. We sought to explore if chitosan (0, 0.1, 0.5, or 1%) incorporation could be used as a means to control S1P release from alginate hydrogels. With increasing chitosan incorporation, hydrogels exhibited significantly denser pore structure and stiffer material properties. While 0.1 and 0.5% chitosan gels demonstrated slower respective release of S1P, release from 1% chitosan gels was similar to alginate gels alone. Furthermore, 0.5% chitosan gels induced greater sprouting and directed migration of outgrowth endothelial cells (OECs) in response to released S1P under hypoxia in vitro. Overall, this report presents a platform for a novel alginate-chitosan hydrogel of controlled composition and in situ gelation properties that can be used to control lipid release for therapeutic applications.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, 1 Shields Avenue, Davis, CA, USA.
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Williams
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, 1 Shields Avenue, Davis, CA, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Campbell
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, 1 Shields Avenue, Davis, CA, USA.
authors.forename: Hessam
authors.initials: H
authors.lastname: Gharaviram
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, 1 Shields Avenue, Davis, CA, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Madrigal
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, 1 Shields Avenue, Davis, CA, USA. esilva@ucdavis.edu.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Silva
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008246:Lysophospholipids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020100:Hydrogels; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D020723:Glucuronic Acid; D048271:Chitosan; D013110:Sphingosine
keywords: Composite hydrogel; Controlled release; Homing; Lipid; Outgrowth endothelial cell; Proangiogenic factors; Sphingosine-1-phosphate (S1P)