Drug-Initiated Synthesis and Processing of Mupirocin–PLGA Conjugates for Biodegradable Antibacterial Scaffolds

Abstract Mupirocin–poly(lactic-co-glycolic acid) (Mup-PLGA) conjugates were developed via drug-initiated ring-opening polymerization to create biodegradable scaffolds with local antibacterial activity. Conjugate composition and molecular weight were controlled to tune degradation behavior, and materials were processed into porous solvent-cast scaffolds and electrospun mats. Degradation studies showed that molecular weight, copolymer ratio, and plasticizer content governed structural evolution, while the processing method had a limited effect. No measurable release of free mupirocin was detected during degradation. Despite this, antibacterial activity was observed under direct-contact conditions and correlated with conjugate composition, reflecting mupirocin content along polymer chains. Electrospun scaffolds exhibited limited diffusible activity, attributed to higher surface area. Overall, the materials did not behave as classical release systems but showed surface-mediated antibacterial effects instead. These findings position Mup-PLGA conjugates as a platform for wound dressings combining tunable degradation with local antimicrobial functionality, potentially reducing exposure to subinhibitory free antibiotic concentrations. Extract-based MTT testing showed mean cell viability above the 70% criterion for both electrospun mats and the nonplasticized SC7 scaffold, whereas TEC-containing solvent-cast scaffolds were cytotoxic.