title: StarPEG-Heparin Hydrogels to Protect and Sustainably Deliver IL-4.
abstract: A major limitation for the therapeutic applications of cytokines is their short half-life time. Glycosaminoglycans (GAGs), known to complex and stabilize cytokines in vivo, are therefore used to form 3D-biohybrid polymer networks capable of aiding the effective administration of Interleukin-4, a key regulator of the inflammatory response. Mimicking the in vivo situation of a protease-rich inflammatory milieu, star-shaped poly(ethylene glycol) (starPEG)-heparin hydrogels and starPEG reference hydrogels without heparin are loaded with Interleukin-4 and subsequently exposed to trypsin as a model protease. Heparin-containing hydrogels retain significantly higher amounts of the Interleukin-4 protein thus exhibiting a significantly higher specific activity than the heparin-free controls. StarPEG-heparin hydrogels are furthermore shown to enable a sustained delivery of the cytokine for time periods of more than two weeks. Primary murine macrophages adopt a wound healing supporting (M2) phenotype when conditioned with Interleukin-4 releasing starPEG-heparin hydrogels. The reported results suggest that GAG-based hydrogels offer valuable options for the effective administration of cytokines in protease-rich proinflammatory milieus such as chronic wounds of diabetic patients.
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069, Dresden, Germany.
authors.forename: Lucas
authors.initials: L
authors.lastname: Schirmer
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069, Dresden, Germany.
authors.forename: Passant
authors.initials: P
authors.lastname: Atallah
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069, Dresden, Germany.|Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Fetscherstraße 105, 01307, Dresden, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
authors.affiliation: Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, 01069, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Freudenberg
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D006025:Glycosaminoglycans / Q000378:metabolism; D006207:Half-Life; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry*; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D015847:Interleukin-4 / Q000008:administration & dosage / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D006025:Glycosaminoglycans; D020100:Hydrogels; D015847:Interleukin-4; D011092:Polyethylene Glycols; D006493:Heparin
keywords: Interleukin-4; biohybrid hydrogels; cytokines; glycosaminoglycan; stabilization; sustained release