Covalently integrated curcumin turns piperazine-based polyurethane-urea into a scaffold-as-drug for infected bone repair.

Abstract

Infected bone defects are difficult to repair because bacterial persistence, excessive inflammation, oxidative stress, and impaired osteogenesis occur simultaneously. Conventional drug-loaded scaffolds often rely on physical loading, which can cause burst release and premature drug depletion. Here, we developed a scaffold-as-drug platform by covalently integrating curcumin (CUR) into a 3D-printable piperazine-based polyurethane-urea (P-PUU) backbone. CUR served as a reactive phenolic chain extender, while piperazine provided urea-forming structural segments. Spectroscopic and chromatographic analyses supported polymer formation and CUR incorporation, and molecular simulations indicated reduced chain mobility and stronger interchain association after CUR integration. The resulting CUR-P-PUU scaffolds retained interconnected porosity, improved apparent wettability, enhanced mechanical performance, and provided sustained degradation-associated CUR availability. Although physically blended CUR/P-PUU showed stronger short-term osteogenic responses in vitro, consistent with greater early CUR availability, CUR-P-PUU exhibited a more sustained CUR-availability profile during scaffold degradation. CUR-P-PUU supported BMSC viability, inhibited methicillin-resistant Staphylococcus aureus (MRSA), suppressed LPS-induced inflammatory cytokines, and promoted osteogenic differentiation. In a rat MRSA-infected calvarial defect model, CUR-P-PUU reduced bacterial burden, was associated with a less inflammatory and more pro-reparative local immune phenotype, and enhanced bone formation and mineralization. This study establishes covalent small-molecule integration as a materials-driven strategy for infection-resilient bone regeneration in a printable biodegradable scaffold.

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