Enzyme-powered PLGA micromotors for biofilm eradication and long-term regrowth inhibition

Bacterial biofilms are dense structures composed of microbial communities and their extracellular polymeric substances (EPS), posing severe challenges in the field of biomedical engineering. These EPS matrices form a "mucus protective barrier", endowing biofilms with robust resistance to antibiotics, biocides and immune responses. Conventional eradication strategies such as disinfectants and enzymatic cleaners have inherent limitations including easy induction of microbial drug resistance, failure to penetrate the EPS barrier, and inability to prevent the rapid regeneration of biofilms. In this study, a fully biodegradable enzyme-driven PLGA micromotors (PLGA MMs) system was developed via a hydroxyapatite (HAP)-stabilized oil-in-water Pickering emulsion templating method, with azithromycin (AZM) and catalase (CAT) encapsulated within the PLGA matrix. The micromotors achieve deep biofilm penetration by virtue of catalase-driven propulsive force, while the biodegradable PLGA matrix enables the sustained release of AZM for several weeks, effectively eliminating residual bacteria and inhibiting biofilm regeneration. Experimental results demonstrated that the PLGA MMs could efficiently eradicate Staphylococcus aureus biofilms (with only 3.2% residual biofilm biomass remaining), kill residual bacteria within the biofilms (with a bacterial survival rate of merely 2.3%), and completely inhibit biofilm regrowth for up to 14 days. Furthermore, the PLGA MMs exhibited favorable biocompatibility (with a CAT activity retention rate of > 88.98% and a hemolysis rate of < 5%). This synergistic "disruption-sustained inhibition" strategy provides a novel and translationally promising platform for combating recalcitrant biofilm infections.