title: Selection of proangiogenic ascorbate derivatives and their exploitation in a novel drug-releasing system for wound healing.
abstract: The pathophysiology leading to delayed wound healing is complex and efficient therapeutic approaches for accelerated wound healing currently do not exist. We developed a novel drug-eluting platform for the potential use in wound dressings. Here, we report on the potential of eluting ascorbic acid-2-phosphate (ASC-2P), a highly stable variant of ascorbic acid, to induce angiogenesis and to promote collagen synthesis by fibroblasts. The drug-eluting platform device (DEPD) consists of biocompatible polymeric layers comprising polyethylene terephtalate, polyvinyl alcohol (PVA), and polyurethane with PVA as the solvent for ASC-2P. The angiogenic potential of ASC-2P was evaluated in the endothelial cell tube formation assay (TFA) and in the chorion allantoic membrane (CAM) model. Collagen synthesis by ASC-2P-stimulated fibroblasts was determined by Sirius Red staining. ASC-2P significantly induced angiogenesis in five independent TFA and CAM assays and induced collagen synthesis in two different fibroblast cell lines. The eluting kinetics of ASC-2P was determined by the ultraviolet NanoDrop method and the functional 2,2'-Azinobis-(3-ethylbenzthiazolin-6-sulfonic acid) method. Eluting profiles showed a continuous release in the range of biologically effective concentrations >10 days. This is the first report showing the proangiogenic- and collagen-promoting features of ASC-2P. DEPD loaded with ASC-2P ought to be further evaluated as wound dressings or as supplementary pads for topical treatment of delayed wound healing in preclinical studies.
authors.affiliation: Department of Traumatology and Hand Surgery, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Ulla
authors.initials: U
authors.lastname: Stumpf
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Denise
authors.initials: D
authors.lastname: Klassert
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
authors.forename: Jens
authors.initials: J
authors.lastname: Altrichter
authors.forename: Joachim
authors.initials: J
authors.lastname: Windolf
authors.forename: Julian
authors.initials: J
authors.lastname: Hergenröther
authors.forename: Martin
authors.initials: M
authors.lastname: Scholz
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003094:Collagen / Q000096:biosynthesis; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D043925:Angiogenesis Inducing Agents; C011669:ascorbate-2-phosphate; D003094:Collagen; D001205:Ascorbic Acid