title: Drug-sensing hydrogels for the inducible release of biopharmaceuticals.
abstract: Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF(121) for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Ehrbar
authors.forename: Ronald
authors.initials: R
authors.lastname: Schoenmakers
authors.forename: Erik H
authors.initials: EH
authors.lastname: Christen
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry; D049933:Aminocoumarins / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D027081:DNA Gyrase / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry; D008422:Materials Testing; D015394:Molecular Structure; D009675:Novobiocin / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D049933:Aminocoumarins; D001672:Biocompatible Materials; D027081:DNA Gyrase; D003692:Delayed-Action Preparations; D020100:Hydrogels; D009675:Novobiocin; D042461:Vascular Endothelial Growth Factor A; D000099166:Polyacrylamides; C467484:VEGFA protein, human; C004628:coumermycin