Hydrophobic ciprofloxacin derivatives as dual-functional photoinitiators for photocurable polylactide scaffolds in treatment of infected bone defects

Abstract

Osteomyelitis, a severe bone infection, poses significant challenges due to antibiotic resistance and limited efficacy of conventional treatments, which often rely on non-degradable carriers with burst antibiotic release. Biodegradable scaffolds with intrinsic antimicrobial functionality offer a promising alternative combining structural support, sustained therapy, and bone tissue regeneration. In this study, novel hydrophobic derivatives of the antibiotic ciprofloxacin-allylciprofloxacin (Cpf-Allyl) and vinylbenzylciprofloxacin (Cpf-VBC) – were synthesized and evaluated as photoinitiators for one- and two-photon polymerization (1PP and 2PP) of star-shaped polylactide (SS-PLA) to obtain scaffolds designed for bone regeneration. Both derivatives retained antimicrobial activity comparable to unmodified ciprofloxacin against key pathogens, including S. aureus and E. coli. Cpf-VBC demonstrated favorable photophysical properties for 2PP: 40% higher absorbance at 263 nm and lower fluorescence quantum yield (8% vs. 10% for Cpf-Allyl), approaching the efficiency of the commercial photoinitiator Bis-b. All photosensitive resins achieved high degrees of conversion (DC ≥ 60%) for the 1PP-method. In contrast, Cpf-VBC-based 2PP scaffolds showed a significantly lower DC (29 ± 4%) compared to both Cpf-Allyl-based and Bis-b-based scaffolds (∼58%). However, the use of Cpf-VBC resulted in increased surface hydrophilicity of the scaffolds, as evidenced by lower water contact angles (62 ± 2°) and a higher polar component of surface energy. All fabricated scaffolds promoted the proliferation of mesenchymal stromal cells and their efficient osteogenic differentiation supported by scaffold mineralization. The scaffolds exhibited topographical and mechanical properties suitable for bone tissue engineering, with a Young's modulus (262–377 MPa) in the range of human cancellous bone.