A dual-functional 3D scaffold with an imidazolium-based interface for non-antibiotic therapy and enhanced osseointegration in infected bone defect.

Abstract

Infected bone defects pose a significant clinical challenge due to the need for prolonged antibiotic therapy and multiple bone grafting procedures, which often lead to antibiotic overuse and increased patient burden. In this study, we developed a multifunctional 3D-printed polycaprolactone (PCL)/β-tricalcium phosphate (TCP) composite scaffold functionalized with a novel imidazolium-based cationic polymer (PIm⁺) encapsulated within a gelatin methacryloyl (GelMA) hydrogel interface. The resulting PCL/TCP+ scaffold exhibits optimized hydrophilicity and mechanical strength for bone regeneration. The early, sustained release of PIm⁺provides potent broad-spectrum bactericidal activity against bothStaphylococcus aureus(S. aureus) andEscherichia coli(E. coli) by efficiently disrupting bacterial membranes. Simultaneously, the TCP component facilitates long-term osteogenic differentiation of bone marrow mesenchymal stem cells through the sustained release of calcium and phosphate ions. In a clinically relevant rat infected calvarial defect model, the scaffold achieves near-complete bacterial clearance by day 7 and promotes robust bone bridging within 12 weeks. This integrated platform offers a promising, personalized strategy for infected bone repair by significantly reducing reliance on systemic antibiotics and providing a highly effective dual-functional microenvironment for infected bone regeneration.