Dual-function nanoparticles enzymatically conjugated with a custom-made polyurethane hydrogel for chronic wound treatment

Hydrogels are attractive drug delivery systems with the potential to protect their cargo and control its release. In particular, hydrogels based on synthetic polymers are gaining increasing interest by virtue of their controllable chemistry, ease of modification, and reproducibility. Moreover, the presence of specific side chains and pending functional groups in the polymer structure allows for the conjugation of drugs and other compounds resulting in improved control over drug release. Enzymes that catalyse reactions in a very specific way could also be used to control the conjugation of compounds to the polymeric chains to improve reproducibility and biocompatibility of the conjugation process. This contribution describes an innovative system for drug delivery comprising a bioartificial supramolecular hydrogel based on a customised polyurethane and α- cyclodextrins, and nanoparticles, for application in the treatment of chronic wounds. The system has the potential to reduce inflammation and eradicate infection by virtue of dual-function nanoparticles which incorporate cobalt as antimicrobial agent, and phenolated lignin as antioxidant. The nanoparticles are enzymatically conjugated to the hydrogel by means of the amine side groups exposed along the backbone of the ad-hoc synthesised polyurethane. The oxidase enzyme laccase is exploited to oxidize the phenol groups of lignin, to allow their interaction with the amines on the hydrogel. The effects of nanoparticles conjugation to the hydrogel are studied through gelification tests, stability tests, and rheology. Moreover, the release of nanoparticles from the hydrogel and their effects on patients’ wound fluids and against relevant bacterial strains are analysed in vitro.