Engineering of Biodegradable and Excretable Inflammation-Resolving Materials

摘要

Uncontrolled or chronic inflammation contributes to the pathogenesis of manyacute/chronic diseases, such as acute organ injury, COVID-19, and atherosclerosis.Intrinsically bioactive materials are promising for regulating the responsemagnitude and duration of inflammation, but their translation remainschallenging. Herein, the engineering of a series of inflammation-resolvingmaterials by rationally integrating different functional modules into a hydrolyzablescaffold is reported. The obtained functional materials can assembleinto potent anti-inflammatory micelles capable of eliminating different typesof reactive oxygen species, releasing bioactive molecules, and simultaneouslyhydrolyzing into water-soluble and excretable compounds. Cellularly,these micelles effectively inhibit the migration, activation, and production ofmolecular mediators in inflammatory cells. Benefiting from the small size andhigh bioactivity, the developed micelles efficiently accumulate in the kidneysof mice with acute kidney injury (AKI) and efficaciously alleviate AKI. Bioactivemicelles also demonstrate desirable targeting and superior efficacies in micewith acute liver failure. Mechanistically, inhibition of oxidative damage, attenuationof inflammatory cell infiltration and activation, and promoting resolutionof inflammation mainly account for beneficial therapeutic effects of micelles.Moreover, preliminary studies reveal the excellent safety of micelles. Consequently,the bioactive materials represent a new type of efficacious, safe, scalable,and affordable therapy for a broad spectrum of inflammatory diseases.