title: A biohybrid hydrogel for the urate-responsive release of urate oxidase.
abstract: Functional biomaterials that detect and correct pathological parameters hold high promises for biomedical application. In this study we describe a biohybrid hydrogel that detects elevated concentrations of uric acid and responds by dissolution and the release of uric acid-degrading urate oxidase. This material was synthesized by incorporating PEG-stabilized urate oxidase into a polyacrylamide hydrogel that was crosslinked by the uric acid-sensitive interaction between the uric acid transcription factor HucR and its operator hucO. We characterize the uric acid responsiveness of the material and demonstrate that it can effectively be applied to counteract flares of uric acid in a mouse model. This approach might be a first step towards a biomedical device autonomously managing uric acid burst associated to gouty arthritis and the tumor lysis syndrome.
authors.affiliation: Faculty of Biology, BIOSS Centre for Biological Signalling Studies, University of Freiburg, Schänzlestrasse 1, 79104 Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Geraths
authors.forename: Marie
authors.initials: M
authors.lastname: Daoud-El Baba
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Charpin-El Hamri
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
mesh_terms: D000818:Animals; D003850:Deoxyribonuclease I / Q000737:chemistry; D016503:Drug Delivery Systems; D057809:HEK293 Cells; D006801:Humans; D020100:Hydrogels; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry; D014503:Urate Oxidase / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020100:Hydrogels; D014527:Uric Acid; D011092:Polyethylene Glycols; D014503:Urate Oxidase; D003850:Deoxyribonuclease I
keywords: Biohybrid material; Closed-loop control; DNA-protein interaction; Gouty arthritis; Stimulus-sensing material