title: Microfluidic synthesis of pharmacologically responsive supramolecular biohybrid microgels.
abstract: Biohybrid hydrogels that change their mechanical properties in response to pharmacological cues hold high promises as externally controlled drug depots for biomedical applications. In this study, we devise a generically applicable method for the synthesis of micrometer-scale, injection-ready biohybrid materials. We use droplet-based microfluidics to generate monodisperse pre-microgel fluid droplets, wherein which we react fluorescein-modified 8-arm poly(ethylene glycol) with a thiol-functionalized humanized anti-fluorescein single chain antibody fragment and vinylsulfone-functionalized 8-arm poly(ethylene glycol), resulting in the formation of stable, narrowly dispersed supramolecular microgels (30 and 150 μm diameter). We demonstrate that the addition of free fluorescein to these microgels results in a weakening of their hydrogel structure, eventually leading to its disintegration. This method of formation of pharmacologically responsive biohybrid hydrogels in an injection-ready formulation is a pioneering example of a general approach for the synthesis of biohybrid hydrogel-based drug depots for biomedical applications.
authors.affiliation: Faculty of Biology, Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Schänzlestrasse 18, 79104, Freiburg, Germany.
authors.forename: Désirée
authors.initials: D
authors.lastname: Hövermann
authors.forename: Torsten
authors.initials: T
authors.lastname: Rossow
authors.forename: Raphael J
authors.initials: RJ
authors.lastname: Gübeli
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seiffert
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
mesh_terms: D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry*; D057127:Single-Chain Antibodies / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D057127:Single-Chain Antibodies; D011092:Polyethylene Glycols
keywords: drug depot; hydrogel; poly(ethylene glycol); single-injection vaccination; stimulus-responsive