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.

Rising influence of synthetic biology in regenerative medicine

“…Such innovative biomaterials, developed in the last decade, include novel synthetic peptide-based biomaterial scaffolds [56], interactive biohybrid materials [57][58][59] and the development of semi-synthetic ECMs from covalently cross-linked biodegradable hydrogels [60]. This semi-synthetic ECM is designed to allow the inclusion of the specific biological cues required to simulate the complexity of the ECM of a given tissue.…”

Visual optical biosensors based on DNA-functionalized polyacrylamide hydrogels

“…An example is insulin release from hydrogels in response to glucose concentration change for treating diabetes. Towards this goal, biomolecular interactions need to be introduced inside the hydrogels [27][28][29][30]. Many previous works have employed peptides, protein enzymes and antibodies for molecular recognition.…”

Application of Synthetic Biology to Regenerative Medicine

“…Ehrbar et al [68,69] engineered a smart hydrogel where increasing concentrations of antibiotic resulted in the dissolution of the gel and the release of an embedded growth factor in a time-and dose-dependent manner (Figure 4). Such controlled dissolution is valuable for tissue engineering, allowing an artificial scaffold to be replaced, over time, with a new natural one [70].…”