Combinatorial Polyacrylamide Hydrogels for Preventing Biofouling on Implantable Biosensors

ABSTRACT Biofouling on the surface of implanted medical devices severely hinders device functionality and drastically shortens device lifetime. Poly(ethylene glycol) and zwitterionic polymers are currently considered “gold standard” device coatings to reduce biofouling. To discover novel anti-biofouling materials, we created a combinatorial library of polyacrylamide-based copolymer hydrogels and screened their ability to prevent fouling from serum and platelet-rich plasma in a high-throughput parallel assay. We found certain non-intuitive copolymer compositions exhibit superior antibiofouling properties over current gold standard materials, and employed machine learning to identify key molecular features underpinning their performance. For validation, we coated the surfaces of electrochemical biosensors with our hydrogels and evaluated their anti-biofouling performance in vitro and in vivo in rodent models. Our copolymer hydrogels preserved device function and enabled continuous measurements of a small-molecule drug in vivo better than gold standard coatings. The novel methodology we describe enables the discovery of anti-biofouling materials that can extend the lifetime of real-time in vivo sensing devices.