Selection of proangiogenic ascorbate derivatives and their exploitation in a novel drug-releasing system for wound healing

• Published in: Wound repair and regeneration 2011-09, Vol.19 (5), p.597-607
• Main Authors: Stumpf, Ulla, Michaelis, Martin, Klassert, Denise, Cinatl, Jindrich, Altrichter, Jens, Windolf, Joachim, Hergenröther, Julian, Scholz, Martin
• Format: Article
• Language: English
• Subjects: Angiogenesis Inducing Agents - pharmacology; Animals; Ascorbic Acid - analogs & derivatives; Ascorbic Acid - pharmacology; Cell Survival; Cells, Cultured; Chick Embryo; Chorioallantoic Membrane - blood supply; Collagen - biosynthesis; Drug Delivery Systems; Fibroblasts - drug effects; Fibroblasts - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Humans; In Vitro Techniques; Neovascularization, Physiologic - drug effects; Wound Healing - drug effects; Wound Healing - physiology
• ISSN: 1067-1927; 1524-475X
• DOI: 10.1111/j.1524-475X.2011.00718.x

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.