Letter abstract
Nature Materials 7, 800 - 804 (2008)
Published online: 10 August 2008 | doi:10.1038/nmat2250
Subject Categories: Polymers | Biological materials | Biomedical materials
Drug-sensing hydrogels for the inducible release of biopharmaceuticals
Martin Ehrbar1, Ronald Schoenmakers2, Erik H. Christen2, Martin Fussenegger2 & Wilfried Weber2
Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function1, 2. 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 factor3. 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 VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials5, 6, 7, 8, 9 as smart devices for spatiotemporally controlled delivery of drugs within the patient.
- Department of Cranio-Maxillofacial Surgery, University Hospital Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland
- Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, 4058 Basel, Switzerland
Correspondence to: Wilfried Weber2 e-mail: wilfried.weber@bsse.ethz.ch
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